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Chronic Kidney Disease in Kidney Cancer Patients
Anthony Chang, MDUniversity 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 non-
cardiovascular 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, MSLa 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 >20%
• Diabetic nephropathy 10-20%
• Focal segmental GS 2-9%
• Thrombotic microangiopathy 3-5%
• AA amyloidosis 3%
• Atheroembolic disease 2%
• IgA nephropathy 2%
• Membranous nephropathy <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 Mesangial sclerosis Mesangial hypercellularity
Crescent / fibrinoid necrosis Segmental Sclerosis 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 fibrosis / tubular atrophy
Interstitial inflammation Acute tubular injury
Vessels
Intimal fibrosis Hyalinosis Thrombus
Atheroembolus 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
Bijol V, et al. Am J Surg Pathol, 2006; 30: 575-584..
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
J Urol 2010, 184: 1872-1876.
– Extent of global glomerulosclerosis correlates with the rate of renal function decline in radical nephrectomy specimens
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 (anti-GBM) 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
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 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 (>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): ___________________
Proposed Parameter
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?