Cystic Diseases of the Kidney Workup

Updated: Mar 28, 2017
  • Author: Thomas Patrick Frye, DO; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
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Workup

Laboratory Studies

Developmental cystic disease (MCDK)

In MCDK, because of the associated ureteral obstruction, the patient may have pyelonephritis in spite of an unremarkable urine specimen. However, blood cultures and clinical examination should readily suggest this diagnosis.

Autosomal dominant polycystic kidney disease (ADPKD)

Diagnosis is primarily clinical, but, in presymptomatic patients with a family history, gene linkage analysis can be used in combination with sonography for screening. [6] The combination of these two modalities can achieve a detection sensitivity of 88.5% in patients younger than 30 years and 100% in patients older than 30 years. Some authors suggest that until effective treatments become available, the adverse effects from presymptomatic diagnosis in children (psychological, educational, career, and insurability issues) outweigh the benefits. [27]

Autosomal recessive polycystic kidney disease (ARPKD)

Genetic testing for mutations at PKHD1 is currently available, with 80-85% detection rates in patients with strong clinical and/or histopathological evidence. [8] Current guidelines do not recommend the use of PKHD1 mutational analysis as a first-line diagnostic test, due to the large number of similar disorders that involve mutations in other genes (eg, HNF1B, which is responsible for disorders including hepatorenal fibrocystic disease). [28] However, early prenatal diagnosis is feasible only by single-gene testing. Additionally, genotype is currently not a predictor for clinical course. Correlations are complicated by inheritance of different mutations from each parent.

On prenatal ultrasound, Erger et al reported sonographically visible kidney cysts in only 3% of ARPKD cases. Pulmonary hypoplasia, oligohydramnois or anhydramnios, and kidney enlargement were associated with a significantly worse neonatal prognosis. [29]

A neonate may have hyponatremia during the first few weeks of life. The infant subsequently may demonstrate diminished urine osmolality (ie, < 500 mOsm/kg) secondary to reduced concentrating ability and metabolic acidosis secondary to decreased urinary acidification capacity. The patient may also have recurrent pyuria. Bilirubin and hepatic enzyme values may also be elevated. Annual complete blood cell counts (CBCs) should be performed, with attention to the platelet count, due to the risk of portal hypertension and splenic dysfunction.

See also Imaging in Autosomal Recessive Polycystic Kidney Disease

Juvenile nephronophthisis (JNPHP) and medullary cystic kidney disease (MCKD)

The urine has elevated sodium levels and low specific gravity with minimal proteinuria and normal sediment. Renal tubular acidosis may result in alkalotic urine and systemic acidosis. Genetic linkage analysis may be used to establish the diagnosis.

Systemic disease with associated renal cysts

Prenatal screening is available for tuberous sclerosis (TS) if the diseased allele can be identified in an affected family member. In the absence of this, no reliable genetic marker for TS is known. Genetic screening techniques can be used to identify likely disease-causing mutations in 58-68% of cases.

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Imaging Studies

Developmental cystic renal disease (MCDK)

Prenatal sonography is the diagnostic tool of choice and can be used to identify MCDK as early as 15 weeks' gestation. [16] Sonography demonstrates multiple variably sized, noncommunicating cysts outlined by hyperechoic intervening renal parenchyma. [30] The corresponding ureter and renal pelvis are typically not visualized. See the image below.

A prenatal sonogram of a fetus with a multicystic A prenatal sonogram of a fetus with a multicystic dysplastic kidney. The right kidney is appreciated as a large multicystic paraspinal mass. The left kidney and bladder are normal, and a normal amount of amniotic fluid is present.

After birth, serial (one within days of life and another 1 month later) high-quality sonography should be performed to confirm the diagnosis and to evaluate the contralateral kidney and the rest of the urinary tract. [20]

Intravenous pyelography (IVP) may show a nonfunctioning kidney or a deformed mass with faint specks of contrast corresponding to small areas of functioning renal tissue. No collecting system or ureter is identified. Shell-like calcifications outlining some of the cysts may be noted.

Ureteral obstruction with collecting system dilatation may be difficult to differentiate from MCDK. In these cases, nuclear medicine functional studies can be helpful and demonstrate a rim of functional tissue in the obstructive cases. [16]

An association with contralateral ureteropelvic junction obstruction, as well as with renal ectopia, exists. Previously, voiding cystourethrography (VCUG) was routinely performed to rule out reflux into the contralateral kidney. More recent data suggest, however, that VCUG is of little value if serial high-quality ultrasonography findings are consistent with MCDK and demonstrate a normal bladder and contralateral kidney. [20]

Autosomal dominant polycystic kidney disease

Typically, cysts first are observed radiographically in the second to third decades of life. With progression, the kidneys become enlarged with multiple spherical fluid-filled cysts (1-3 cm) that are appreciated readily with computed tomography (CT), ultrasonography, or magnetic resonance imaging (MRI). The Consortumium for Radiologic Imaging for the Study of Polycycstic Kidney Disease has demonstrated a mean increase in renal volume of 63.4 mL per year in an exponential fashion in their cohort of 200 patients. [31]

Sonographic criteria for ADPKD depend on patient age. Sonographic diagnosis in individuals at 50% risk for the disease involves two unilateral or bilateral cysts in patients younger than 30 years, two cysts in each kidney in individuals aged 30-59 years, and four cysts in each kidney in individuals 60 years or older. See the images below.

CT examination of the abdomen of a 70-year-old wom CT examination of the abdomen of a 70-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) is shown. The kidneys are bilaterally enlarged with multiple cysts.
CT scan of the same patient (70-year-old woman wit CT scan of the same patient (70-year-old woman with autosomal dominant polycystic kidney disease [ADPKD]) demonstrating multiple hepatic cysts.

Debris may produce heterogeneous cyst attenuation, and cysts may have fluid-fluid levels from hemorrhage. Hemorrhagic cysts demonstrate unenhanced CT attenuation values of 40-100 Hounsfield units (HU). Symptomatic episodes of gross hematuria underestimate the true incidence of hemorrhage, as up to 90% of patients with ADPKD have cysts that are hyperdense on CT. Calcification may be observed in the cyst walls or in the parenchyma between cysts, and nephrocalcinosis or nephrolithiasis is observed in as many as 50% of patients. Calcification likelihood increases with age and is fairly common in patients older than 50 years.

Contrast enhancement of the renal parenchyma provides an indication of the amount of functioning renal parenchyma that remains. The likelihood of hepatic cysts increases with age; 40% of patients demonstrate liver cysts by the fourth decade of life, and nearly 90% of patients have them by the sixth decade of life.

When ADPKD presents in childhood, ultrasonography may reveal hyperechoic enlarged cystic kidneys, a pattern that may be difficult to differentiate from ARPKD. In this situation, family history and possible ultrasonography of the parents' or grandparents' kidneys is recommended.

When malignancy or infected cysts are a concern, a contrast-enhanced CT scan can be performed.

Recommendations do not exist for intracranial aneurysm screening but it is advised, especially in patients with a positive family history. [16] The screening can be readily accomplished noninvasively with magnetic resonance angiography (MRA).

Autosomal recessive polycystic kidney disease

Second-trimester ultrasound imaging of bilateral hyperechogenic kidneys with poor corticomedullary differentiation suggests a diagnosis of ARPKD. Other features include enlarged kidneys that maintain their reniform shape and have increased echogenicity. Finding large echogenic kidneys with poor corticomedullary differentiation and coexisting liver disease by ultrasound is sufficient for diagnosis. Genetic testing is needed only in cases ambiguous by imaging. [32]

With severe renal disease, absence of urine in the bladder, oligohydramnios, pulmonary hypoplasia, and a small thorax may be observed. At birth, neonates require assisted ventilation, and pneumothorax is common.

In children, kidney size is typically at least two standard deviations greater than normal and diffusely hyperechogenic. In 29% of cases, bilateral cysts of 5-7 mm are found at presentation. [33] Loss of corticomedullary differentiation may be observed, and small cysts oriented in a radial pattern in the distribution of the collecting ducts may be evident. The cysts tend to enlarge over time.

If severe oligohydramnios is seen, fetal MRI should be used, as it better shows renal anatomy. ARPKD is associated with signal void in a contracted bladder on a T2-weighted sequence. [34] Furthermore, MRI can be used to predict nonsurvival. In one series of 46 fetuses, a ratio of MRI-calculated lung volume to gestational age of 0.90 (in fetuses with a gestational age of over 26 weeks) demonstrated a sensitivity and specificity of 77.8% and 95%, respectively, for predicting mortality. [35]

Precontrast CT scan images show enlarged, smooth kidneys with low attenuation (likely representing the large volume of fluid in the collecting tubules). Renal calcifications are frequently noted. With contrast, poor opacification of the kidneys may be observed (with severe renal failure), and the physician may appreciate radial streaks of contrast extending from the cortical surface to the inner medulla. The classic radial streak pattern is best appreciated with IVP.

Liver disease can be visualized with ultrasonography, which demonstrates hepatomegaly with echogenic parenchyma (secondary to fibrosis), hepatic cysts, and dilatation of the peripheral hepatic ducts with fibrous bridging. [16] Magnetic resonance cholangiography is more sensitive in detecting dilated biliary ducts. Patients at the age of 5 years should have abdominal ultrasound performed, with followup every 2-3 years. [32]

Once a diagnosis is made by imaging, serial assessment by ultrasound should be performed every 2-3 weeks. Particular attention should be paid to the onset of oligohydramnios, as it is a predictor for nonsurvival. In one series, oligohydramnios in the presence of kidney size >4 standard deviations above the mean was associated with 100% mortality in the perinatal period. [36]

Glomerulocystic kidney disease

The kidneys appear either hypoplastic or normal in size on sonography and maintain their reniform shape. Cysts are small (< 1 cm) and are observed in an echogenic cortex; the medulla is spared. Corticomedullary differentiation is lost. [9]

On CT and MRI, glomerulocystic kidney disease (GCKD) appears as numerous small cortical cysts. These do not enhance with gadolinium during MRI. [37]

Juvenile nephronophthisis and medullary cystic kidney disease

Sonography and CT scan reveal bilaterally shrunken kidneys. On sonography, cysts are observed at the corticomedullary junction in a background of diffusely echogenic renal parenchyma. [16]

Acquired cystic renal disease

Acquired renal cystic disease (ARCD) can be diagnosed if involvement is bilateral, with at least four cysts per kidney. Once cysts are observed sonographically, further evaluation with contrast-enhanced CT scan is indicated to rule out carcinoma. Contrast-enhanced helical CT scanning has 96% sensitivity and 95% specificity in detecting carcinoma. In patients who cannot tolerate ionic contrast, MRI may be useful to evaluate for neoplasms. See the image below.

This CT scan demonstrates acquired renal cystic di This CT scan demonstrates acquired renal cystic disease (ARCD) in a 70-year-old man who is dialysis-dependent. The CT scan demonstrates bilateral atrophic kidneys with multiple renal cysts.

Medullary sponge kidney

In medullary sponge kidney (MSK), findings on plain radiographs may be normal, or radiographs may reveal medullary nephrocalcinosis (represented by multiple discrete calculi clustered in the renal pyramids). At least one renal calculus (typically < 5 mm) is often observed.

IVP demonstrates a "bouquet of flowers" or "paintbrush" pattern. Ectatic tubules are observed as dense streaks of contrast material radiating from the calyces, while papillary cysts are observed as round opacifications in the papillae. The "brush" pattern of the ectatic tubules must be differentiated from a dense papillary blush, which may be observed in healthy patients; with low-osmolar contrast, papillary blush is observed in as many as 13% of routine IVPs. A greater than 0.3-mm cylinder or streak diameter has been recommended to help differentiate between pathologic tubular ectasia and normal variant physiology. CT scan may show calcifications at the corticomedullary junction.

Simple cyst

The most clinically significant aspect of a simple cyst is differentiating it from carcinoma. Simple-cyst walls occasionally calcify and, thus, radiographically mimic malignancy. Sonographic features that support the diagnosis of simple cyst include an anechoic round mass with a smooth and sharply demarcated wall and through-transmission with strong posterior wall echo.

If the ultrasonography findings are suspicious or equivocal, a CT scan is warranted. CT scan criteria for a benign cyst include (1) sharp demarcation cyst with a smooth thin wall, (2) homogeneous fluid within the cyst (typically with density < 20 HU, although higher measurements may be found with a benign proteinaceous cyst or if hemorrhage is present in a benign cyst), and (3) no contrast enhancement. Enlargement of the cyst can raise the concern of malignancy, although the natural history of benign renal cysts does show progressive slow enlargement.

Computed tomography

CT remains the gold standard for investigation of renal cysts, as it has been able to delineate malignancy and is the basis of the intitial Bosniak classification. Predictors of malignancy include thickened irregular wall or septa, enchancing soft tissue, and internal cyst heterogeneity. Of these factors, septal and nodular enchancements provide a sensitivity of 100% and sensitivity of 86%. Furthermore, contrast enhancement of 42 Hounsfield units (HU) between the corticomedullary phase and the pre-contrast phase is an independent predictor of malignancy. [38]

The use of CT is more difficult for small and intermediate lesions. New techniques to better define these lesions have surfaced, including dual-energy CT, thinner slicing (3 mm), and delayed-contrast CT. [39] Dual-energy CT is better able to expose vascularity which is a predictor for malignancy. Thinner slicing at 3 mm used in overlapping sections improves detection of renal cysts < 5 mm. Finally, using delayed contrast enhancement can better differentiate renal cell carcinomas from non-neoplastic cysts. [40] These new techniques help address challenging cases of psuedoenhancement.

Magnetic resonance imaging

MRI can be used for the classification of renal cysts as studies have confirmed that MRI results correlate with histopathology. Where MRI gains favor over CT is in the evaluation of cystic fluid; different compositions of fluid, such as blood or protein, have higher predictors of malignancy. These factors can provide upgrading on Bosniak criteria based on CT. [41]

New techniques focus on multiparametric MRI with focus on diffusion weighted imaging (DWI). DWI measures the motion and diffusion of water, which will be different in malignant and benign tissue. Further investigation of this technique is needed due to lack of standardization and determination of the appropriate amount of weighting (b value).

Bosniak classification

Bosniak has described a classification scheme for renal cysts based on CT scan findings. The categories are as follows [42] :

  • Category I (simple cyst) - Thin wall without septa, calcifications, or solid components; measures water density (< 20 HU) and does not enhance (< 2% chance of malignancy)

  • Category II (minimally complex cyst) - Thin wall (< 1 mm) and no enhancement; may contain 1 or 2 hairline-thin septa, fine calcification, or short segment of slightly thickened calcification; includes high-attenuation lesions that are smaller than 3 cm (Malignancy rates in series range from 0-14%. Series with higher malignancy rates include IIF lesions.)

  • Category IIF (indeterminate) - Minimal enhancement and/or thickening of a hairline-thin smooth septum or wall; mildly thickened or nodular calcification; no enhancing soft-tissue components; includes nonenhancing high-attenuation lesions that are 3 cm or larger (approximately 20% likelihood of malignancy)

  • Category III (suspicious indeterminate) - Multilocular lesion with multiple enhancing septae, uniform wall thickening, nodularity, or thick or irregular calcification (30-60% likelihood of malignancy)

  • Category IV (malignant) - Contains enhancing (>10 HU) large nodules or clearly solid components (>90% likelihood of malignancy)

Another option for patients with renal impairment or allergy to iodinated contrast is contrast-enhanced ultrasound (CE-US). CE-US is a technique that has been shown to be equivalent to CT, and in one experience CE-US was found to be better than CT in the diagnosis of malignancy in Bosniak IIF and III renal cysts. [43]

A multi-institutional review of Bosniak IIF and III cystic lesions has been performed. The malignancy rate of resected Bosniak IIF lesions was 25% (4/16) and that of Bosniak III lesions was 54% (58/107). Thirteen percent of Bosniak IIF lesions progressed at follow-up with half of them being malignant at resection. Risk factors for having malignancy seen with a Bosniak III lesions were: history of primary renal malignancy, coexisting Bosniak category IV lesion and/or solid renal mass, and multiplicity of Bosniak III lesions. Importantly, all patients had localized disease with either Bosniak IIF or III lesion. [44]

The Bosniak classification system greatly varies from observer to observer, particularly in the differentiation of Bosniak category II from Bosniak category III lesions. Additionally, a significant portion of Bosniak category II lesions may prove to be malignant. In one series, 14% of lesions so categorized were found to be malignant. Thus, adherence to classification standards and recommended follow-up care, particularly for Bosniak category IIF, should be strictly followed.

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Procedures

In the evaluation of an intermediate renal cyst, fine-needle aspiration has a limited role. Some centers report a sensitivity of more than 70% for core biopsy and cyst aspiration with cytology.

The enzyme CA9 is being studied as a new marker for clear cell renal cell carcinoma. One report showed that CA9 can be detected in the fluid of malignant cystic, but not benign, renal tumors. This marker may be useful to help guide decisions of treatment versus observation in select populations. [45]

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Histologic Findings

Developmental cystic renal disease

In multicystic dysplastic kidney, cystic dysplasia is a subset of renal dysplasia. In this form, typical renal configuration is lost. The disease is usually a unilateral process, but it ranges from involving a portion of one kidney to completely involving both kidneys.

Grossly, the kidney appears to be an enlarged mass of cysts among immature primitive tissue, often with surrounding fibrosis and an atretic collecting system. [20] The ureter is often stenotic or hypoplastic, and the renal artery is often small or absent. [16]

Microscopy reveals small areas of otherwise normal-appearing glomeruli and tubules interspersed with cysts lined with cuboidal epithelium and surrounded by collars of spindle cells. The cysts are filled with proteinaceous or sanguinous fluid. In addition, immature-appearing cartilage is often present in the tissue. See the image below.

Cut surface of a nephrectomy specimen from a patie Cut surface of a nephrectomy specimen from a patient with a multicystic dysplastic kidney (MCDK).

Inherited cystic renal disease

In autosomal dominant polycystic kidney disease, the kidneys are enlarged and distorted by multiple renal cysts. Cystic kidneys can exceed 40 cm in length and weigh as much as 5 kg. Cysts range in size from a few millimeters to several centimeters and are distributed relatively uniformly through the medulla and cortex. Cyst fluid ranges from clear to hemorrhagic.

Microscopic evaluation shows cystic dilatations in all segments of the nephron, with loss of connection to the tubule. While all segments are involved, the cysts derived from the collecting duct are the largest and most numerous. [46] The cysts are lined by a single layer of flattened-to-cuboidal epithelium. The intervening parenchyma demonstrates interstitial fibrosis, tubular atrophy, chronic inflammation, and vascular sclerosis. See the images below.

External surface of a nephrectomy specimen from a External surface of a nephrectomy specimen from a patient with autosomal dominant polycystic kidney disease (ADPKD).
Cut surface of the same nephrectomy specimen from Cut surface of the same nephrectomy specimen from a patient with autosomal dominant polycystic kidney disease (ADPKD).

In autosomal recessive polycystic kidney disease, the kidneys are enlarged bilaterally, but a reniform shape is preserved. With neonatal presentation, the kidneys may be 10-20 times normal size. Radial cysts are typically smaller than 3 mm in diameter and extend perpendicularly from the papillary tips to the surface of the cortex.

Microscopically, the cysts are lined by flattened (undifferentiated) epithelium and represent fusiform dilation of collecting tubules that retain their connection to the afferent and efferent tubules. The parenchyma adjacent to the cysts progressively develops interstitial fibrosis and glomerulosclerosis.

The liver is grossly enlarged, and microscopic evaluation demonstrates bile duct dilatation and periportal fibrosis. This histologic pattern is known as congenital hepatic fibrosis (CHF) and is always present in ARPKD. However, CHF is not specific to this disease.

GCKD is characterized by dilatation of Bowman space without involvement of the related tubule. The dilated Bowman spaces are lined by a flattened epithelium and contain rudimentary glomerular tufts. [9]

Juvenile nephronophthisis and medullary cystic kidney disease are characterized by thickening and wrinkling of the tubular basement membrane, tubular atrophy, and interstitial fibrosis, leading to bilaterally small kidneys with a pitted surface. [10] The renal cortex is uniformly thinned, and cysts are located at the corticomedullary junction and are derived from the collecting ducts and distal tubules. [7]

The number of cysts varies (5-50), and cysts measure from several millimeters to 1 cm. However, 25% of cases do not involve grossly visible cysts. Microscopic evaluation demonstrates that the cysts are lined by single layers of cuboidal epithelium.

Systemic disease with associated renal cysts

In tuberous sclerosis, renal cysts are uncommon and usually not extensive, but diffuse cystic renal disease that involves both the cortex and the medulla is occasionally noted, particularly in children. Cysts vary in size from several millimeters to 3 cm. Diffuse renal cystic disease grossly resembles kidneys affected by ADPKD. Microscopically, the cysts are lined by large eosinophilic cells with enlarged hyperchromatic nuclei. [3]

In von Hippel-Lindau syndrome (VHLS), multiple renal cysts develop bilaterally. Renal cysts are lined with glycogen-rich, clear-appearing cells (similar to those observed with grade I clear-cell renal cell carcinoma [RCC]). Atypia and epithelial hyperplasia are common in the cysts.

Acquired cystic renal disease

In acquired renal cystic disease, gross evaluation of early disease reveals cortical cysts filled with clear fluid. Cysts are usually smaller than 0.5 cm in diameter but may be as large as 3 cm in diameter. With more advanced disease, medullary cysts are observed. The disease may progress to numerous diffusely distributed cysts and resemble a small kidney affected by ADPKD.

Microscopy reveals a flattened, hyperplastic tubular epithelial lining. Foci of epithelial hyperplasia or renal adenomas are common. The remaining renal tissue exhibits sclerotic glomeruli, atrophic tubules, and interstitial fibrosis. Oxalate crystals are common in the walls of cysts.

In medullary sponge kidney, gross evaluation reveals normal-sized kidneys, which may be unremarkable with the exception of at least one enlarged and pale renal pyramid. The disease is bilateral in 70% of cases. Microscopic evaluation reveals dilated collecting ducts lined by cuboidal or flattened epithelium. The cystlike cavities range in size from 1-7.5 mm (usually 1-3 mm) and are present in the papillary portions of the pyramids. Roughly half of the dilated channels contain calcifications. Inflammatory infiltrate is found adjacent to the dilated tubules.

Simple cysts measure 1-5 cm in diameter and are filled with clear fluid. The cysts are usually lined by a flattened layer of epithelium, although they may lack an epithelial lining. See the image below.

Nephrectomy specimen from a patient with a large b Nephrectomy specimen from a patient with a large benign simple cyst.
Cut section of nephrectomy specimen demonstrating Cut section of nephrectomy specimen demonstrating renal cell carcinoma (RCC), with an adjacent simple cyst.
Close-up photograph of the cut surface of the same Close-up photograph of the cut surface of the same nephrectomy specimen demonstrating a simple cyst adjacent to a renal cell carcinoma (RCC).
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