Interaction of Hepatitis C Infection and Renal Disease: Persons infected with hepatitis C virus (HCV) can develop kidney disease as a result of extrahepatic manifestation of HCV or as a disease process independent of the HCV infection. In addition, hemodialysis has been a risk factor for acquiring HCV infection, with 8.4% of hemodialysis patients in the United States having chronic HCV in the year 2000. Several studies have shown that patients on chronic hemodialysis have an increased overall mortality risk if they have chronic hepatitis C infection (when compared with those on dialysis who do not have hepatitis C infection). There are also some data showing that chronic hepatitis C may be a risk factor for developing renal cell carcinoma. Chronic hepatitis C infection has also been associated with an accelerated course of renal disease in HIV-infected persons. Extrahepatic manifestations related to HCV, including immune complex-related renal disease, can require urgent HCV treatment to resolve or prevent further organ damage.
Definitions and Classification: As part of evaluating and treating patients with hepatitis C and renal disease, it is import to first determine the stage of the patient’s renal disease, a process that utilizes some of the following definitions.
- Chronic Kidney Disease (CKD): Chronic kidney disease is defined based on the presence of either kidney damage or decreased kidney function for three or more months, irrespective of cause.
- Glomerular Filtration rate (GFR): GFR is generally considered to be the best index of overall kidney function. The GFR varies in normal individuals by age and sex, dietary protein intake, and possibly by race-ethnicity. The normal value for GFR is approximately 130 and 120 mL/min/1.73 m2 for men and women, respectively. The widely accepted threshold defining a decreased GFR is less than 60 mL/min per 1.73 m2; kidney failure is defined as a GFR less than 15 mL/min/1.73 m2 or treatment by dialysis (Figure 1). The GFR is equal to the sum of the filtration rates in all of the functioning nephrons, but since the GFR cannot be measured directly, it is usually estimated from serum markers. The gold standard for assessment of GFR is the renal inulin clearance test, but this method is highly complex and not practical for routine clinical purposes. Accordingly, several methods, including the Cockcroft-Gault formula and the Modification of Diet in Renal Disease (MDRD), have been utilized in clinical practice to estimate GFR.
- Creatinine Clearance (CrCl): The creatinine clearance is a widely used test to estimate the glomerular filtration rate (eGFR). The creatinine clearance, however, overestimates the GFR since creatinine is both filtered by the glomeruli and secreted in the renal tubules. The Cockcroft-Gault formula is commonly used in clinical practice to estimate the creatinine clearance based on the serum creatinine, patient age, body mass in kilograms, and sex (Figure 2). Normal values are 95 to 145 mL/min in men and 75 to 115 mL/min in women. This formula is less accurate in weight extremes. A more accurate, but less practical, determination of creatinine clearance can be made with a 24-hour urine collection. The creatinine clearance is then calculated by dividing the 24-hour urine creatinine by the serum creatinine; the 24-hour urine creatinine is equal to the urine creatinine concentration multiplied by urine volume. There are several limitations to the 24-hour urine creatinine clearance that can cause inaccuracies, such as an incomplete urine collection.
- Staging of Kidney Disease: Guidelines such as the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines state that among patients who are diagnosed using the criteria described above, staging of CKD should be done according to the cause of disease, category of eGFR and category of albuminuria. The KDIGO classifies kidney disease based on the cause, patient’s GFR and albuminuria categories (Figure 3), with an overall prognosis generated based on the both of these categories (Figure 4).
Evaluation of Patients with Chronic HCV and Renal Insufficiency: Serum creatinine should be measured and creatinine clearance or GFR should be estimated as part of a pre-treatment assessment for HCV patients. The CKD stage should be determined if renal function is abnormal. Complete blood count should be obtained as well, to assess for pre-treatment anemia.