Opportunities for treatment of the hepatitis C virus-infected patient with chronic kidney disease

Table 1 Direct acting antiviral agents: Dose and use in chronic kidney disease IV, V, end stage renal disease and kidney transplant patients

Medication dose	Use in CKD stage IV, V and ESRD	Use in kidney transplant patients - interactions with Immunosuppressant
Sofosbuvir/Simeprivir	CKD IV - GFR 15-29 mL/min: Not recommended	Decrease in TAC levels with Simeprivir
400 mg daily/150 mg daily	CKD V - GFR < 15 mL/min: Not recommended	Increase levels of both CyA and Simeprivir
	ESRD (dialysis): Not recommended	Increase or decrease levels of SRL with Simeprivir
		No changes in TAC, CyA and SRL with Sofosbuvir
Sofosbuvir/Velpatasvir	CKD IV - GFR 15-29 mL/min: Not recommended	Increase in TAC levels with Velpatasvir
400 mg/100 mg daily	CKD V - GFR < 15 mL/min: Not recommended	No changes in CyA levels with Velpatasvir
	ESRD (dialysis): Not recommended	Increase in SRL levels with Velpatasvir
		No changes in TAC, CyA and SRL with Sofosbuvir
Sofosbuvir/Daclastavir	CKD IV - GFR 15-29 mL/min: Not recommended	No changes in TAC levels with Daclastavir
400 mg daily/60 mg daily	CKD V - GFR < 15 mL/min: Not recommended	No changes in CyA levels with Daclastavir
	ESRD (dialysis): Not recommended	Increase in SRL levels with Daclastavir
		No changes in TAC, CyA and SRL with Sofosbuvir
Sofosbuvir/Ledipasvir	CKD IV - GFR 15-29 mL/min: Not recommended	No changes in TAC levels with Ledipasvir
400 mg/90 mg daily	CKD V - GFR < 15 mL/min: Not recommended	No changes in CyA levels with Ledipasvir
	ESRD (dialysis): Not recommended	No changes in SRL levels with Ledipasvir
		No changes in TAC, CyA and SRL with Sofosbuvir
Ombitasvir/Paritaprevir/ritonavir/Dasabuvir	CKD IV - GFR 15-29 mL/min: Dose adjustment not required	Increase in TAC levels (ritonavir)
12.5 mg/75 mg/50 mg × 2 tabs/250 mg × 2 tabs	CKD V - GFR < 15 mL/min: Dose adjustment not required	Increase in CyA levels (ritonavir)
	ESRD (dialysis): Dose adjustment not required. Dialysis population studied. Minimal adverse events in patients with advanced CKD and ESRD on hemodialysis	Increase in SRL levels (ritonavir)
		No changes in TAC, CyA and SRL with Ombitasvir/Paritaprevir/Dasabuvir
Grazoprevir/Elbasvir	CKD IV - GFR 15-29 mL/min: Dose adjustment not required	Increase in TAC levels with Grazoprevir
100 mg/50 mg daily	CKD V - GFR < 15 mL/min: Dose adjustment not required	Use of both CyA and Grazoprevir increase levels of
	ESRD (dialysis): Dose adjustment not required. Dialysis population studied. Minimal adverse events in patients with advanced CKD and ESRD on hemodialysis	Grazoprevir, contraindicated to use together
		Increase in SRL levels with Grazoprevir

GFR: Glomerular filtration rate; CKD: Chronic kidney disease; ESRD: End stage renal disease; TAC: Tacrolimus; CyA: Cyclosporine; SRL: Sirolimus.

Table 2 Direct acting antiviral agent options for patients with kidney disease

HCV/kidney disease consideration	Complications and observations from HCV infection	DAA options	Other DAA options/notes
HCV related acute glomerulonephritis with or without cryoglobulinemia	HCV has tropism for B-cells with subsequent: Mixed cryoglobulinemia	Sofosbuvir 400 mg/d combined with	Can use: Grazoprevir 100 mg/elbasvir 50 mg/d
		Simeprivir 150 mg/d
		Daclastavir 60 mg/d	Ombitasvir 12.5 mg/paritaprevir 75 mg/ritonavir 50 mg × 2 tabs/dasabuvir 250 mg × 2 tabs
	Glomerulonephritis with distinct histological patterns: Membranous nephropathy	Velpatasvir 100 mg/d
		Ledipasvir 90 mg/d
	Membranoproliferative GN
The HCV-infected patient with stage 1-3a chronic kidney disease (GFR > 45 mL/min)	Increased risk for CKD development	Sofosbuvir 400 mg/d combined with	Can use
	Increased rate of CKD progression to ESRD	Simeprivir 150 mg/d	Grazoprevir 100 mg/elbasvir 50 mg/d
		Daclastavir 60 mg/d
	Higher mortality rate	Velpatasvir 100 mg/d	Ombitasvir 12.5 mg/paritaprevir 75 mg/ritonavir 50 mg × 2 tabs/dasabuvir 250 mg × 2 tabs
		Ledipasvir 90 mg/d
The patient with advanced stage 3 and stage 4/5 chronic kidney disease (GFR < 45 mL/min)	Receiving an anti-HCV positive allograft decreases waiting times for a deceased donor kidney	Sofosbuvir 400 mg/d combined with	Sofosbuvir not recommended with GFR < 30 mL/min
		Simeprivir 150 mg/d
		Daclastavir 60 mg/d	Can use
		Velpatasvir 100 mg/d	Grazoprevir 100 mg/Elbasvir 50 mg/d
		Ledipasvir 90 mg/d
			Ombitasvir 12.5 mg/Paritaprevir 75 mg/ritonavir 50 mg × 2 tabs/dasabuvir 250 mg × 2 tabs
The ESRD patient on dialysis	Increased risk of mortality and poor clinical outcomes in ESRD patients Increased cardiovascular risk	Grazoprevir 100 mg/Elbasvir 50 mg/d	Grazoprevir/elbasvir, ombitasvir/paritaprevir/ritonavir/dasabuvir, Dialysis population studied
		Ombitasvir 12.5 mg/Paritaprevir 75 mg/ritonavir 50 mg × 2 tabs/dasabuvir 250 mg × 2 tabs
			Minimal adverse events in patients with advanced CKD and ESRD on hemodialysis
The kidney transplant recipient with eGFR > 30 mL/min	DAA use after kidney transplant is safe and well tolerated with SVR > 97%	Sofosbuvir 400 mg/d combined with	Can use
		Simeprivir 150 mg/d	Grazoprevir 100 mg/elbasvir 50 mg/d (caution with cyclosporin)
		Daclastavir 60 mg/d
		Velpatasvir 100 mg/d	Ombitasvir 12.5 mg/paritaprevir 75 mg/ritonavir 50 mg × 2 tabs/dasabuvir 250 mg × 2 tabs
		Ledipasvir 90 mg/d

DAA: Direct-acting antiviral agent; GFR: Glomerular filtration rate; CKD: Chronic kidney disease; ESRD: End stage renal disease; HCV: Hepatitis C virus; DAA: Direct-acting antiviral; SVR: Sustained viral response.