Chronic Kidney Disease in Kidney Cancer Patients

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Chronic Kidney Disease in Kidney Cancer Patients

• Anthony Chang, MD
• University of Chicago Medical Center

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Outline

• Non-Neoplastic Kidney Diseases in Kidney Cancer
• Harmful
• Common
• Underappreciated
• Review common medical renal diseases associated
  with renal cancer

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Chronic Kidney Disease (CKD)

• Previously known as chronic renal failure
• Defined as GFR lt60 ml/min per 1.73 m2
• May progress to end-stage renal disease
• Involves 25 of renal cell carcinoma (RCC)
  patients prior to nephrectomy
• Diabetes and hypertension are independent risk
  factors for RCC

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Chronic Kidney Disease (CKD)

• ? risk of CKD after radical compared with partial
  nephrectomy
• ? risk of cardiovascular and non-cardiovascular
  death

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American Urological Association

• 2009 - T1 tumors (lt7 cm) should be treated with
  partial nephrectomy
• Emerging data that T2 tumors should also be
  treated with nephron sparing surgery

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• Despite mounting evidence that PN is an
  effective and preferable approach to the T1 renal
  mass, it remains markedly underutilized in the
  USA and abroad. The overzealous use of radical
  nephrectomy for T1 tumors must now be considered
  detrimental to the long term health of the kidney
  tumor patient.

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2004 US Renal System Data

• Expected life span on dialysis
• 20 24 years 14.6 years
• 60 64 years 4.3 years
• 70 74 years 3.1 years
• 80 84 years 2.2 years
• RCC 5 year survival rates
• Stage 1 gt90
• Stage 2 75-90
• Stage 3 59-70
• Stage 4 lt10 (median 16-20 mos)

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• As I spoke, the family seemed to relax visibly,
  and began to break into smiles. Oh, thats
  wonderful news, wonderful news! I smiled too,
  automatically, although I did not think my newsa
  biopsy finding of advanced glomerulosclerosis,
  irreversible kidney failurehad been so
  wonderful. It was true that this particular
  kidney biopsy had been done because of heavy
  proteinuria and newly diagnosed kidney failure in
  a man with a lung nodule the working diagnosis
  had been a paraneoplastic membranous nephropathy,
  and the specter of lung cancer had been hanging
  over the scene for the last few days. My news
  made the possibility of cancer recede. The nodule
  eventually was found to be benign, and we were
  left to deal with the aftermath of the not-cancer
  diagnosis, the good news that wasnt.
• If the one-year mortality for new end-stage
  kidney failure exceeds that for most new cancer
  diagnoses, why is it that this family, like many
  others, dreaded the latter more than the former?

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• I became very close with the patient who
  reacted with such relief to the diagnosis of
  advanced kidney disease rather than cancer. I saw
  him progress, quickly and inexorably, to
  dialysis-requiring kidney failure. I watched him
  suffer with infections, fatigue, confusion, and
  cramps. He lost his appetite, and became weak and
  bedbound. He died less than a year after I met
  him. To the end, I dont think that he or his
  family ever understood that the news I had
  brought was bad, or that kidney failure itself
  had been the final blow to his fragile health.
  Perhaps it was for the best that they did not
  really understand.
• Then again, thats what oncologists used to say,
  in whispers, outside the rooms of patients who
  were pretending not to listen.
• Dena E. Rifkin, MD, MS
• La Jolla, California

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Non-Neoplastic Renal Diseases Kidney Cancer
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Non-Neoplastic Kidney Disease Cancer

• 24 cases (9.8)
• 19 Diabetic nephropathy
• 3 Thrombotic microangiopathy
• 1 Focal segmental glomerulosclerosis
• 1 Sickle cell nephropathy
• 21 (88) not originally diagnosed
• Of 147 pathology residency programs, 98 responded
  only 35 (36) require renal pathology rotation

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Non-Neoplastic Kidney Disease Cancer

• Cedars Sinai Medical Center LA (2010 USCAP
  online abstract)
• 311 nephrectomies
• 66 nephrosclerosis (41 or 24 of total were
  mild)
• 7.4 - Diabetic nephropathy
• 4.8 - Focal segmental glomerulosclerosis
• 3 - Miscellaneous (amyloid, GN, atheroemboli,
  etc.)

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Non-Neoplastic Kidney Disease Cancer

• Weill Cornell Medical College (2011 USCAP
  abstract)
• 216 nephrectomy cases
• 47 (21.7) new pathologic diagnoses
• 21 diabetic nephropathy
• 11 hypertensive nephropathy
• 6 focal segmental glomerulosclerosis
• 2 collapsing glomerulopathy
• Arteriolar sclerosis predictive of renal function
  decline

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Non-Neoplastic Kidney Disease Cancer

• 110 tumor nephrectomy (60 prospective)
• 38 - Normal
• 24 - Diabetic nephropathy
• 28 - Severe scarring
• Misc (IgA, collapsing GP, amyloid, etc)

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Incidence in TN specimens

• Arterionephrosclerosis gt20
• Diabetic nephropathy 10-20
• Focal segmental GS 2-9
• Thrombotic microangiopathy 3-5
• AA amyloidosis 3
• Atheroembolic disease 2
• IgA nephropathy 2
• Membranous nephropathy lt1

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Grossing Nephrectomy Specimens

• Should you obtain a fresh tissue sample for IF
  and EM?
• Order the PAS/Jones silver stain on the
  non-neoplastic kidney tissue block

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Algorithm

• Identification of glomerular abnormalities
• First, light microscopy!
• Glomeruli
• Tubules
• Interstitium
• Vessels

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Glomeruli

• Normal Mesangial sclerosis
  Mesangial hypercellularity

Crescent / fibrinoid necrosis Segmental
Sclerosis Endocapillary hypercellularity
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Algorithm

• If glomerular abnormalities present,
• Consider Congo red
• Immunofluorescence microscopy (IgG, IgA, IgM,
  kappa/lambda light chains, albumin) on paraffin
  tissue sections
• Decreased sensitivity compared with frozen tissue
• Immunohistochemistry
• Electron microscopy from paraffin block
• Preservation/processing artifact

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Tubules / Interstitium
Normal Interstitial fibrosis /
tubular atrophy
Interstitial inflammation Acute tubular injury
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Vessels
Intimal fibrosis Hyalinosis
Thrombus
Atheroembolus Vasculitis
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Diabetic Nephropathy

• Diabetes is a risk factor for RCC
• 8 of American adults c diabetes
• 10-20 of RCC patients have diabetes
• DN in up to 8-20 of TN specimens
• Diabetic nodular glomerulosclerosis predicts
  progression of CKD
• Treatment Strict blood glucose control

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Diffuse Mesangial Sclerosis
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Nodular Mesangial Sclerosis
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Capsular Drop
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Arteriolar Hyalinosis
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Nodular Glomerulosclerosis

• Differential diagnosis
• Diabetic nephropathy
• Amyloidosis
• Monoclonal Immunoglobulin Deposition Disease
• Light chain deposition disease
• Light and heavy chain deposition disease
• Fibrillary GN
• Immunotactoid glomerulopathy
• Idiopathic nodular glomerulosclerosis
• Associated with hypertension and smoking

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Amyloidosis

• 3 of RCC with AA amyloidosis
• Rare cases of AL amyloid and other amyloid
  forming proteins
• Treatment removal of neoplasm
• Proteinuria may indicate recurrent or metastatic
  disease

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Amyloidosis
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Arterionephrosclerosis

• AKA Hypertensive nephropathy / nephrosclerosis
• Hypertension in 25-60 of RCC pts
• Tumor nephrectomy (TN) specimens
• 40 with arteriosclerosis and no TI scarring
• 20 with arteriosclerosis and TI scarring
• gt20 global glomerulosclerosis predicts
  progression of CKD

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Glomerulosclerosis
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Underestimating global glomerulosclerosis
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Significance of Global Glomerulosclerosis

• Bijol V, et al
• Presence of gt20 global glomerulosclerosis or
  nodular diabetic glomerulosclerosis predicted an
  increase of 0.5 mg/dL in serum creatinine 6
  months after surgery

Bijol V, et al. Am J Surg Pathol, 2006 30
575-584..
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• Extent of global glomerulosclerosis correlates
  with the rate of renal function decline in
  radical nephrectomy specimens

J Urol 2010, 184 1872-1876.
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Interstitial fibrosis / tubular atrophy
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Arteriosclerosis
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Focal Segmental Glomerulosclerosis

• 2 to 9 of TN specimens
• Often associated with hypertension,
  arteriosclerosis, and parenchyma scarring
• May be secondary to reduction of functional
  nephrons
• Proteinuria, nephrotic-range (gt3 g/day)
• IF negative
• EM podocyte foot process effacement

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Focal Segmental Glomerulosclerosis
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Crescentic GN

• Etiologies
• Pauci-immune (ANCA-associated) GN
• Anti-glomerular basement membrane (anti-GBM) GN
• Immune complex-mediated GN
• IgA nephropathy
• Lupus nephritis
• Membranoproliferative GN
• Post-infectious GN
• Etc.

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Pauci-immune crescentic GN

• Uncommon in the setting of kidney cancer
• 80 with positive ANCA titer
• Clinicopathologic entities
• Churg-Strauss syndrome
• Granulomatosis with polyangiitis (Wegener)
• Microscopic polyangiitis

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Crescentic GN
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Pitfall JGA hyperplasia
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Pitfall Collapsing Glomerulopathy
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Pauci-immune crescentic GN
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Actual Parameter
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Proposed Parameter
Non-Neoplastic Kidney (evaluate using PAS and/or
Jones methenamine silver stain check all that
apply) ____ Insufficient tissue (partial
nephrectomy specimen with lt5 mm of adjacent
non- neoplastic kidney ____ Sufficient tissue
__ No significant pathologic alterations of the
glomeruli, tubules, interstitium, or vessels __
Significant pathologic alterations Glomeruli
(fill all that apply) ____ of glomeruli
with global sclerosis (0-100) ____ Glomerular
disease (specify) ________________ ____ Other
Tubulointerstitial compartment (check all that
apply) ____ No significant abnormalities ___
_ Interstitial fibrosis/tubular atrophy, mild
(5-25) ____ IF/TA, moderate (26-50) ____
IF/TA, severe (gt50) ____ Other
tubulointerstitial diseases (specify)
______________ Vessels (check all that
apply) ____ No significant abnormalities ___
_ Arteriosclerosis (mild lt25 occlusion) ____
Arteriosclerosis (moderate 26-50
occlusion) ____ Arteriosclerosis (severe gt50
occlusion) ____ Other vascular injuries
(specify) ___________________
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Future Directions

• Improve coordinated care between urologists and
  nephrologists
• Refine therapeutic implications of pathologic
  parameters of the non-neoplastic kidney
• Global glomerulosclerosis
• Severity of interstitial fibrosis / tubular
  atrophy
• Severity of arteriosclerosis or
  arteriolosclerosis

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Summary

• Chronic Kidney Disease / End-stage renal disease
  is important
• Non-neoplastic renal diseases are common
• Diabetic nephropathy
• Arterionephrosclerosis
• Examine the non-neoplastic kidney carefully,
  especially with benign tumors!
• Order PAS/Jones silver stains

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Questions?