Chronic Kidney Disease in Kidney
Cancer Patients
Anthony Chang, MD
University of Chicago Medical Center
Outline
•
Non-Neoplastic Kidney Diseases in
Kidney Cancer
–
–
–
•
Harmful
Common
Underappreciated
Review common medical renal
diseases associated with renal cancer
Chronic Kidney Disease (CKD)
•
•
•
•
Previously known as “chronic renal failure”
Defined as GFR <60 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
Chronic Kidney Disease (CKD)
• ↑ risk of CKD after radical compared with
partial nephrectomy
• ↑ risk of cardiovascular and noncardiovascular death
American Urological Association
• 2009 - T1 tumors (<7 cm) should be
treated with partial nephrectomy
• Emerging data that T2 tumors should also
be treated with nephron sparing surgery
“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.”
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 = >90%
 Stage 2 = 75-90%
 Stage 3 = 59-70%
 Stage 4 = <10% (median: 16-20 mos)
“As I spoke, the family seemed to relax visibly, and began to break
into smiles. “Oh, that’s wonderful news, wonderful news!” I smiled
too, automatically, although I did not think my news—a biopsy
finding of advanced glomerulosclerosis, irreversible kidney failure—
had 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
wasn’t.
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?”
“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 don’t 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, that’s 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
Non-Neoplastic Renal Diseases &
Kidney Cancer
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
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.)
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
Non-Neoplastic Kidney Disease & Cancer
• 110 tumor nephrectomy (60 prospective)
•
•
•
•
38% - Normal
24% - Diabetic nephropathy
28% - Severe scarring
Misc (IgA, collapsing GP, amyloid, etc)
Incidence in TN specimens
•
•
•
•
•
•
•
•
Arterionephrosclerosis
Diabetic nephropathy
Focal segmental GS
Thrombotic microangiopathy
AA amyloidosis
Atheroembolic disease
IgA nephropathy
Membranous nephropathy
>20%
10-20%
2-9%
3-5%
3%
2%
2%
<1%
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
Algorithm
• Identification of glomerular abnormalities
– First, light microscopy!
• Glomeruli
• Tubules
• Interstitium
• Vessels
Glomeruli
Normal
Crescent / fibrinoid necrosis
Mesangial sclerosis
Segmental Sclerosis
Mesangial hypercellularity
Endocapillary hypercellularity
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
Tubules / Interstitium
Normal
Interstitial inflammation
Interstitial fibrosis / tubular atrophy
Acute tubular injury
Vessels
Intimal fibrosis
Atheroembolus
Hyalinosis
Thrombus
Vasculitis
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
Diffuse Mesangial Sclerosis
Nodular Mesangial Sclerosis
Capsular Drop
Arteriolar Hyalinosis
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
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
Amyloidosis
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
• >20% global glomerulosclerosis predicts
progression of CKD
Glomerulosclerosis
Underestimating global glomerulosclerosis
Significance of Global Glomerulosclerosis
• Bijol V, et al:
– Presence of >20% 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..
– Extent of global glomerulosclerosis correlates
with the rate of renal function decline in
radical nephrectomy specimens
J Urol 2010, 184: 1872-1876.
Interstitial fibrosis / tubular atrophy
Arteriosclerosis
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 (>3 g/day)
• IF: negative
• EM: podocyte foot process effacement
Focal Segmental Glomerulosclerosis
Crescentic GN
Etiologies
1. Pauci-immune (ANCA-associated) GN
2. Anti-glomerular basement membrane (antiGBM) GN
3. Immune complex-mediated GN
• IgA nephropathy
• Lupus nephritis
• Membranoproliferative GN
• Post-infectious GN
• Etc.
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
Crescentic GN
Pitfall – JGA hyperplasia
Pitfall – Collapsing Glomerulopathy
Pauci-immune crescentic GN
Actual Parameter
Proposed Parameter
Non-Neoplastic Kidney (evaluate using PAS and/or Jones methenamine silver stain;
check all that apply)
____ Insufficient tissue (partial nephrectomy specimen with <5 mm of adjacent nonneoplastic 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 (>50%)
____ Other tubulointerstitial diseases (specify): ______________
Vessels (check all that apply)
____ No significant abnormalities
____ Arteriosclerosis (mild; <25% occlusion)
____ Arteriosclerosis (moderate; 26-50% occlusion)
____ Arteriosclerosis (severe; >50% occlusion)
____ Other vascular injuries (specify): ___________________
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
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
Questions?