1. RENAL DISEASE IN
HEPATITIS C
PATIENTS
By Dr. Ahmed Abdulghany

4. ESSENTIAL MIXED
CRYOGLOBULINEMIA

5. A more accurate term for this type of vasculitis is mixed cryoglobulinemia
syndrome, which refers to primary or idiopathic cryoglobulinemia as well as
cryoglobulinemia associated with autoimmune diseases, malignancy or
infection.

6. TYPES OF CRYOGLOBULINS
 Type I cryoglobulinemia: most often due to underlying multiple myeloma or
Waldenström’s macroglobulinemia
 Type II mixed cryoglobulinemia: most often due to chronic infection with
hepatitis C virus (HCV) although infection with hepatitis B virus and Epstein-
Barr virus has been implicated in some patients.
 Type III mixed cryoglobulinemia: often seen in chronic inflammatory and
autoimmune diseases (such as systemic lupus erythematosus and Sjögren’s
syndrome), lymphoproliferative malignancies, and, in as many as one-half of
cases, HCV infection

7. THE CLINICAL PRESENTATION
Affected patients typically present
with nonspecific systemic
symptoms, palpable
purpura, arthralgias, fever, renal
disease, neuropathy.
On average, renal disease is detected
approximately 2.5 years after disease
onset.

8. 42%
22%
14%
13%
9%
The clinical presentation of the renal disease
Microscopic hematuria and subnephrotic
proteinuria with or without chronic renal
insufficiency
Nephrotic syndrome with or without
chronic renal insufficiency
Acute glomerulonephritis
Chronic kidney disease without significant
urinalysis abnormalities
Acute renal failure
Hypertension was present in
approximately 65% of patients

9. FINDINGS ON RENAL BIOPSY

13. IDIOPATHIC
MEMBRANOPROLIFERATIVE
GN

14.  The association of HCV infection and idiopathic MPGN (ie, in the absence of
cryoglobulinemia) is controversial.
 Although some patients did not have circulating cryoglobulins in the initial
reports of HCV-associated MPGN, the majority subsequently developed
measurable cryoglobulinemia, but not necessarily the extrarenal
manifestations of cryoglobulinemia.

15. POLYARTERITIS NODOSA

16.  Polyarteritis nodosa (PAN) is well described in patients with hepatitis B virus
infection, but also occurs in association with HCV in the absence of
cryoglobulins.

17. CLINICALLY SILENT
GLOMERULAR DISEASE

18.  In addition to symptomatic renal disease, clinically silent glomerular disease
has been described in patients with HCV infection, primarily in those who
under liver transplantation for cirrhosis due to chronic HCV infection.

19. INDICATIONS FOR ANTIVIRAL THERAPY:
 The main indications for therapy are moderate to severe disease
(eg, nephrotic syndrome, elevated plasma creatinine concentration, new
hypertension, fibrosis or tubulointerstitial disease on biopsy) or progressive
disease.
 Acute severe disease — Antiviral therapy should be delayed for two to four
months in patients with (renal failure due to rapidly progressive crescentic
glomerulonephritis, neurologic involvement), particularly those with mixed
cryoglobulinemia, while they undergo more aggressive therapy. In this
setting, patients are initially treated with plasmapheresis, intravenous
methylprednisolone, followed by oral prednisone, and
either cyclophosphamide or rituximab.

20. KDIGO RECOMMENDATIONS:
 The Kidney Disease: Improving Global
Outcomes (KDIGO) clinical practice
guidelines for hepatitis C in chronic kidney
disease were published in 2008. The
guidelines suggest that patients with HCV-
associated glomerular disease be
considered for treatment with antiviral
therapy. The suggested regimen depends
upon eGFR.
 Rituximab — Patients whose disease
manifestations are not controlled by, or are not
appropriate for, interferon and ribavirin may be
candidates for rituximab.
eGFR> 50
Ml/min/1.73m2
• pegylated interferon and ribavirin
eGFR 15 to <50
mL/min per 1.73
m2
• monotherapy with pegylated interferon
eGFR less than 15
mL/min per 1.73
m2
• monotherapy with standard interferon that
is dose adjusted for a glomerular filtration

21. TAKE-HOME MESSAGE:
Many HCV patients have clinically inapparent glomerular disease by biopsy.
HCV-infected patients should be screened for
proteinuria, hematuria, hypertension, and renal function, as well as for
cryoglobulinemia, complement, and rheumatoid factors. A kidney biopsy should
be considered in the setting of significant proteinuria and/or impaired renal
function.