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Acquired Cystic Kidney Disease


First described in 1847 by John Simon in patients with subacute ... tumors filled w/ fluid comes from studies of Madin-Darby Canine Kidney (MDCK) ... – PowerPoint PPT presentation

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Title: Acquired Cystic Kidney Disease

Acquired Cystic Kidney Disease
  • Alicia Notkin
  • February 26, 2008

  • First described in 1847 by John Simon in patients
    with subacute glomerulonephritis (Brights
  • Re-described in 1977 by Dunnill in a study of
    kidneys from autopsies performed on ESRD patients
    on dialysis
  • Has been reported in association with all causes
    of renal disease (except hereditary cystic
    disease b/c of the difficulty in distinguishing
    the two)

Features of acquired cystic kidney disease
  • Multiple
  • Bilateral
  • Usually lt 0.5 cm
  • Positive u/s or CT both kidneys w/ gt/ 4 cysts

Features of acquired cystic kidney disease
  • No FH ADPKD, small/normal sized kidneys, smooth
    contour, cysts are only in the kidney
  • Increased incidence w/ increasing time on
    dialysis 35-50 of dialysis patients overall
  • Men and blacks are at much higher risk

  • Cyst fluid composition resembles that of plasma
    (thought to derive minimally from glomerular
    filtrate primarily from transepithelial solute
    fluid secretion)
  • A brush border is present on the luminal membrane
    of the cysts
  • Above suggest that cysts arise from proliferation
    of proximal tubular epithelial cells

Pathogenesis proposed progression to
adenocarcinoma (Grantham 1991)
Pathogenesis (cont.)
  • Aldosterone hypokalemia seem to stimulate
    tubular cell proliferation, adenoma resection
    in humans has been shown to result in cyst
  • Renal transplantation may ? stabilization or
    regression of cysts by restoring normal renal
    function biochemical milieu
  • However, cyclosporine actually ? ACKD by
    inducing TGF-ß expression, suppressing tumor
    surveillance, possibly by its ischemic effects
    on the native kidneys

Pathogenesis (cont.)
  • In vivo, rats w/ normal kidneys given
    diphenylamine, diphenylthiazole, or
    nordihydroguaiacetic acid develop cysts renal
    epithelium is damaged followed by focal tubule
    dilatation expansion
  • The cyst formation from diphenylthiazole can be
    reversed by stopping the drug
  • The cyst formation from nordihydroguaiacetic acid
    is significantly enhanced by exposure of the
    animals to endotoxins or enteric microbes,
    suggesting the role of secondary factors in cyst

Pathogenesis (cont.)
  • Five-sixths nephrectomy w/ azotemia provides a
    milieu for cyst development in remaining
  • This cyst formation can be enhanced by feeding
    the animals a high protein diet

Pathogenesis (cont.)
  • In vitro Normal Human Kidney (NHK) epithelial
    cells are a good model of cyst development in
  • Cyst formation depends on epidermal growth factor
    (EGF) insulin
  • Adenylate cyclase stimulants ? induction growth
    of cysts

Pathogenesis (cont.)
  • In vitro hydrocortisone promotes cyst formation,
    possibly by increasing the activity of
  • Cysts develop in the proximal tubule
  • Cyst regress when hydrocortisone is removed from
  • As there is no glomerular filtration occurring,
    fluid is accumulating only by secretion across
    the tubular wall

Pathogenesis (cont.)
  • The notion of renal cysts as benign tumors filled
    w/ fluid comes from studies of Madin-Darby Canine
    Kidney (MDCK) epithelial cells (which actually
    more accurately reflect hereditary cystic disease
    rather than acquired cystic disease)
  • Medium alone no proliferation or cysts
  • Add cAMP agonist (results in cell proliferation
    fluid secretion) ? cyst formation
  • Add EGF ? balls of cells
  • Addition of low concentration ouabain (blocks
    Na/K-ATPase) to these cells blocks fluid
    secretion therefore cyst enlargement, but does
    not inhibit proliferation, resulting in a
    dissociation of fluid transport cell
    proliferation, ie. a cellular mass instead of a

  • Hematuria /- pain (or overt hemorrhage)
  • Increase in number size of cysts over time
  • Cyst infection
  • Erythrocytosis
  • Renal cell carcinoma ½ of the time are
    multiple bilateral

Renal cell carcinoma risk factors
  • Smoking 2x risk
  • Occupational exposure to cadmium, asbestos,
    trichloroethylene 1-2x risk
  • Obesity
  • Acquired cystic renal disease 30x risk???
  • Analgesic abuse nephropathy
  • Genetic factors
  • ? Hypertension, prior radiation, sickle cell

Renal cell carcinoma in ESRD
  • Usually develops after 8-10 years of dialysis
  • Occurs in 6 of dialysis patients
  • MF ratio of 71
  • Larger cysts that ? supranormal kidney size ?
    increased risk of transformation (kidneys
    weighing gt 150g are 6x more likely to contain
    carcinoma than smaller size kidneys)
  • Clear cell RCC is much less common as is its
    associated chromosome 3p deletions
  • Seems to have lower metastatic potential
  • May not always be related to acquired cystic

Renal cancer in ACKD compared to the general
population (Marple 1994)
ACKD-associated RCC
  • Serum hepatocyte growth factor (HGF) increases as
    renal failure progresses
  • HGF is also higher in patients who have been on
    dialysis for a longer time
  • HGF mRNA protein, along w/ c-met protein have
    been shown to be upregulated in non-tumor tumor
    regions in ACKD patients w/ RCC

ACKD-associated RCC
  • C-Jun is activated in atypical hyperplastic
    proliferative cells in ACKD is thought to play
    a role in RCC carcinogenesis
  • Bcl-2 overexpression may also have a role in
    tumor development
  • Nadasdy, in 1995, characterized the proliferative
    activity of cyst epithelia in ACKD ( ADPKD
    ARPKD) as high, suggested that these cysts may
    be RCC precursors

Bosniak classification of renal cysts
  • Classifies renal cysts into one of five
    categories based on morphology enhancement on
    CT scan
  • Designation helps w/ diagnosis management of
    the cysts

Bosniak classification (Israel 2005)
Screening for RCC
  • ? Screen dialysis patients for acquired cystic
    kidney disease
  • ? If one decides to screen, should one use
    contrast CT or u/s
  • One recommendation screen w/ u/s, if positive
    for cysts, screen yearly w/ contrast CT
    (particularly if patient has very large cysts)
  • Another recommendation only do radiographic
    screening if patient has new hematuria or flank
    pain or has been on dialysis for a long time or
    has large kidneys from acquired cystic kidney
  • Somewhere in between? screen patients who have
    been on dialysis for 3-5 years

Screening for RCC
  • Probably want to screen on an individual basis
  • Similarly to screening for other malignancies,
    like colon or breast cancer, should probably
    consider comorbidities/overall life expectancy of
    the individual patient

  • Chertow, GM et al. Cost-effectiveness of cancer
    screening in end-stage renal disease. Arch
    Intern Med 1996 1561345.Denton, MD et al.
    Prevalence of renal cell carcinoma in patients
    with ESRD pre-transplantation A pathologic
    analysis. Kidney Int 2002 612201.
  • Farivar-Mohseni, H et al. Renal cell carcinoma
    and end stage renal disease. J Urol 2006
  • Fick, GM et al. Hereditary and acquired cystic
    disease of the kidney. Kidney Int 1994 46951.
  • Grantham, JJ. Acquired cystic kidney disease.
    Kidney Int 1991 40143.
  • Hughson, MD et al. Renal cell carcinoma of
    end-stage renal disease A histopathologic and
    molecular genetic study. J Am Soc Nephrol 1996
  • Ishikawa, I et al. Renal cell carcinoma detected
    by screening shows better patient survival than
    that detected following symptoms in dialysis
    patients. Ther Apher Dial 2004 8468.
  • Ishikawa, I et al. Ten-year prospective study on
    the development of renal cell carcinoma in
    dialysis patients. Am J Kidney Dis 1990 16452.
  • Israel, GM et al. An update of the Bosniak renal
    cyst classification system. Urology 2005
  • Konda, R et al. Expression of hepatocyte growth
    factor and its receptor C-met in acquired renal
    cystic disease associated with renal cell
    carcinoma. J Urol 2004 1712166.
  • LeBrun, CJ et al. Life expectancy benefits of
    cancer screening in the end-stage renal disease
    population. Am J Kidney Dis 2000 35237.
  • Levine, E et al. Natural history of acquired
    renal cystic disease in dialysis patients A
    prospective longitudinal CT study. Am J
    Roentgenol 1991 156501.
  • Lien, YH et al. Association of cyclosporin A
    with acquired cystic kidney disease of the native
    kidneys in transplant recipients. Kidney Int
    1991 44613.
  • MacDougall, ML et al. Predication of carcinoma
    in acquired cystic disease as a function of
    kidney weight. J Am Soc Nephrol 1990 1828.
  • Marple, JT et al. Renal cancer complicating
    acquired cystic kidney disease. J Am Soc Nephrol
    1994 41951.
  • Nadasdy, T et al. Proliferative activity of cyst
    epithelium in human renal cystic diseases. J Am
    Soc Nephrol 1995 51462.
  • Sarasin, FP et al. Screening for acquired cystic
    kidney disease A decision analytic perspective.
    Kidney Int 1995 48207.
  • Truong, LD et al. Renal neoplasm in acquired
    cystic kidney disease. Am J Kidney Dis 1995