**2. Incidence of paraneoplastic syndrome and glomerulopathy in renal cell carcinoma**

The most frequent features of the paraneoplastic syndrome in renal cell carcinoma are hy‐ percalcemia, hypertension and polycythemia. Their prevalence and their causative hor‐ mones and cytokines are listed in Table1 [1].


**Prevalence % Outcomes after resection of renal carcinoma**

IgA nephropathy 11/60 (18%) Remission 6, Azotemia 2 Magyarlaki [21]

IgA/C3 deposition 1/40 (2.5%) N.D. Beaufils [22]

**3. Diagnosis and mechanism of paraneoplastic glomerulopathy**

Recent development or worsening of diabetes mellitus, increased platelet or C-reactive pro‐ tein (CRP), and hypercalcemia also suggests the existence of paraneoplastic syndrome. Glo‐ merulonephritis is considered when urinalysis shows dysmorphic red blood cells and red blood cell casts, as hematuria caused by renal cell carcinoma usually shows isomorphic red blood cells. When proteinuria exceeds 1g per day, it is also better to speculate overlapping glomerulonephritis and examine serological tests including immunoglobulins (IgG, IgA, IgM), complements (CH50, C3, C4), anti-nuclear antibody, and anti-dsDNA antibody. A fi‐ nal diagnosis of glomerulonephritis can only be given by a renal biopsy. Renal cysts or masses identified by renal ultrasonography at the time of renal biopsy should be further in‐ vestigated with CT and MRI. Renal cancer will progress rapidly after steroid therapy for

The diagnosis of paraneoplastic glomerulopathy will be suggested following the criteria; 1) existence of a time relationship between the diagnosis of the glomerulopathy and cancer, 2) no obvious etiology for glomerular diseases, 3) clinical or histological remission of glomerul‐ opathy after complete remission by surgical removal of carcinoma, 4) recurrence of the carci‐

As mentioned above, inactivation of the *VHL* gene by frame-shift mutation is observed in about 60% of sporadic RCC [5]. Activated HIF-1α without VHL protein stimulates hypoxiarelated proteins such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), which lead to tumor growth and trigger angiogenesis (Figure 1) [8,10]. The increased VEGF accelerates glomerular permeability and causes proteinuria, and

noma associated with deterioration of glomerular diseases [3,23].

**Table 2.** Evaluation of glomerulopathy in resected kidneys of renal cell carcinoma patients.

FSGS 5/60 (8%) Azotemia 3

Tubulointerstitial nephritis 16/60 (27) -

**associated with renal cell carcinoma**

glomerulonephritis.

C3/IgM deposition 13/40 (33%) CEA deposition 2/9 (22%) HBs Ag/Ab deposition 6/29(21%)

Diabetic nephropathy 3/60 (5%) Nephrotic /Azotemia 2 Nephrosclerosis 4/60 (7%) Nephrotic /Azotemia 2 **Reference**

http://dx.doi.org/10.5772/53534

113

Paraneoplastic Glomerulopathy Associated with Renal Cell Carcinoma

PTHrP: parathyroid hormone-related peptide, OAF: osteoclast activating factor, TNF: tumor necrosis factor, HCG: hu‐ man chorionic gonadotropin, ACTH: adrenocorticotropin, SAA: serum amyloid A.

**Table 1.** Prevalence and features of paraneoplastic syndromes in renal cell carcinoma.

Paraneoplastic glomerulopathy is believed to be a rare manifestation of the paraneoplastic syndrome. However, immunohistochemical analysis of resected kidneys from 60 patients of renal cell carcinoma revealed 27% of them had immune complex nephropathy including 11 patients (18%) with IgA nephropathy and 5 patients (8%) with focal segmental glomerulo‐ sclerosis [21]. Another immunofluorescence study revealed a positive staining for C3, IgM, or IgA in the mesangial deposits in 35% (14/40) of patients with renal cell carcinoma versus 5.4% in the control subjects [22] (Table 2). Thus, the occurrence of glomerular diseases is not so rare in renal cell carcinoma.


**Table 2.** Evaluation of glomerulopathy in resected kidneys of renal cell carcinoma patients.

**Phenomenon Prevalence % Hormones and cytokines**

Hypertension 40% Renin

Cushing's syndrome 2% ACTH

Galactorrhea Prolactin

Amyloidosis 3-8% SAA protein

Neuromyopathies rare unknown

man chorionic gonadotropin, ACTH: adrenocorticotropin, SAA: serum amyloid A.

**Table 1.** Prevalence and features of paraneoplastic syndromes in renal cell carcinoma.

Abnormal glucose metabolism Insulin, glucagon

Nonmetastatic hepatic dysfunction

Constitutional syndrome (fever, weight

(Stauffer's syndrome)

loss, fatigue)

112 Renal Tumor

Nephropathy

Vasculopathy

Coagulopathy

so rare in renal cell carcinoma.

Polycythemia 1-8% Erythropoietin

Hypercalcemia 13-20% Non-bone metastatic disease 50%, PTH, PTHrP, TGF-α, β,

6% β-HCG

PTHrP: parathyroid hormone-related peptide, OAF: osteoclast activating factor, TNF: tumor necrosis factor, HCG: hu‐

Paraneoplastic glomerulopathy is believed to be a rare manifestation of the paraneoplastic syndrome. However, immunohistochemical analysis of resected kidneys from 60 patients of renal cell carcinoma revealed 27% of them had immune complex nephropathy including 11 patients (18%) with IgA nephropathy and 5 patients (8%) with focal segmental glomerulo‐ sclerosis [21]. Another immunofluorescence study revealed a positive staining for C3, IgM, or IgA in the mesangial deposits in 35% (14/40) of patients with renal cell carcinoma versus 5.4% in the control subjects [22] (Table 2). Thus, the occurrence of glomerular diseases is not

OAF, IL-1, TNF

20-30% TNF-α, IL-6. IL-1, prostaglandins

3-20% Hepatotoxines, lysosomal enzymes stimulating hepatic cathepsins or phosphatases, IL-6
