RENAL DISEASE INHEPATITIS C

PATIENTS

By Dr. Ahmed Abdulghany

ESSENTIAL MIXEDCRYOGLOBULINEMIA

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

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’ssyndrome), lymphoproliferative malignancies, and, in as many as one-half of cases, HCV infection

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.

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

FINDINGS ON RENAL BIOPSY

IDIOPATHICMEMBRANOPROLIFERATIVE

GN

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 extrarenalmanifestations of cryoglobulinemia.

POLYARTERITIS NODOSA

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.

CLINICALLY SILENT GLOMERULAR DISEASE

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.

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 crescenticglomerulonephritis, 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.

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

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.