Viral Nephritides

Question 1

Viral Nephritides

HIV

Answer 1

Human Immunodeficiency Virus
HIV may be associated with various renal lesions including HIV-associated nephropathy (HIVAN), HIV-associated immune complex kidney disease (HIVICK), combined antiretroviral treatment (cART) nephropathy, and TMA.

Question 2

Viral Nephritides

HIV-Associated Nephropathy

Answer 2

Predominantly observed in African American

Associated with advanced HIV (i.e., CD4 < 200 cells/mm3, high viral load)

Question 3

Viral Nephritides

Epidemiology

Answer 3

Clinical Manifestations

Nephrotic range proteinuria, hematuria, normal to enlarged kidneys due to microcyst formation

Question 4

Viral Nephritides

Pathogenesis

Answer 4

Genetic susceptibility: APOL1

Both direct and indirect mechanisms involving HIV are thought to be contributory.

Question 5

Viral Nephritides

Histopathology

Answer 5

LM: collapsing FSGS, tubular microcystic dilatation with proteinaceous casts, and variable acute tubular injury, tubular atrophy, lymphocytic infiltrates, interstitial fibrosis

Question 6

Viral Nephritides

Histopathology

Answer 6

EM: presence of tubuloreticular inclusions in endothelial cell cytoplasm in untreated patients

Question 7

Viral Nephritides

Natural History/Prognosis

Answer 7

Rapid progression to ESRD if untreated

Question 8

Viral Nephritides

Management

Answer 8

Combined antiretroviral therapy (cART), renin–angiotensin system inhibition, corticosteroid therapy if rapid decline in kidney function despite cART and absence of superimposed/opportunistic infections

Question 9

Viral Nephritides

HIV-Associated Immune Complex Kidney Disease

Background

Answer 9

Typically occurs in patients with HIV duration ≥ 10 years

Reported lesions: IgAN, lupus-like GN, MGN, membranous/mesangial proliferative GN, postinfectious GN, immunotactoid/fibrillary GN. NOTE: Since IgAN is rare in African Americans, the presence of IgAN should raise the possibility of concurrent HIV infection.

Question 10

Viral Nephritides

HIV-Associated Immune Complex Kidney Disease

Clinical Manifestations

Answer 10

Nephrotic syndrome, hematuria, HTN; Laboratory findings may be positive for ANA, low C3

Question 11

Viral Nephritides

HIV-Associated Immune Complex Kidney Disease

Histopathology

Answer 11

IF: notable for variable Ig/complement staining, “full house” of Ig may be present

EM: presence of cytoplasmic tubuloreticular structures in endothelial cells

Question 12

Viral Nephritides

Combined Anti-retroviral Treatment (cART) Nephropathy

Answer 12

Nucleotide analog reverse transcriptase inhibitors: mitochondrial dysfunction, Fanconi syndrome, AKI/ATN:

Most well-recognized: tenofovir

Others: lamivudine (3TC), abacavir (ABC), didanosine (ddI)

Question 13

Viral Nephritides

Combined Anti-retroviral Treatment (cART) Nephropathy

Answer 13

NOTE: mitochondrial injury may be seen on EM as giant mitochondria with atypical shapes and broken or absent cristae.

Question 14

Viral Nephritides

Combined Anti-retroviral Treatment (cART)

Answer 14

Protease inhibitors with associated crystal-induced nephropathy/urolithiasis: indinavir, atazanavir, nelfinavir, amprenavir, saquinavir, lopinavir/ritonavir—Indinavir crystals have been described as “plate-like rectangles and fan-shaped or starburst forms”

Question 15

Thrombotic Microangiopathy

Answer 15

May be seen with advanced HIV, not treated with cART

Pathogenesis thought to involve direct HIV attack of endothelial cells

Question 16

Thrombotic Microangiopathy

Answer 16

Affected individuals may have low ADAMTS13 levels, in which case, good response to therapy including corticosteroids and plasma exchange may be expected.

Question 17

Kidney Transplantation in Patients with HIV

Answer 17

May be considered if undetectable viral load and CD4 > 200 cells/mm3

Requirement for immunosuppressive therapy is typically minimal due to drug-drug interactions.

Question 18

Kidney Transplantation in Patients with HIV

Answer 18

NOTE: major drug interaction: protease inhibitors (e.g., darunavir, ritonavir) can markedly increase CNI levels. Less than 5% of usual CNI dose is typically required.

Question 19

Hepatitis B

Associated Lesions

Answer 19

MGN with or without concurrent anti-PLA2R antibodies is most common.

Other notable associated lesions: MPGN (type I), IgAN (in association with chronic liver disease), PAN (IC deposits formed by HBsAg and anti-HBs antibody (IgM) along vessel walls)

Question 20

Hepatitis B

Management

Answer 20

Antiviral therapy: first-line agents include tenofovir, entecavir, and Peg-IFN alfa-2a. Alternatively, adefovir and telbivudine may be used, but at the risk of high rate of resistance. Lamivudine has high rate of resistance and is not preferred.

Question 21

Hepatitis B

Management

Answer 21

Consider corticosteroids (i.e., prednisone 1 mg/kg/d for 2 weeks) and plasma exchange prior to antiviral therapy in PAN.

Nonspecific therapies: RAAS inhibition, BP control

Question 22

Hepatitis B

Management

Answer 22

Do not use rituximab due to association with hepatitis B reactivation. Rituximab may be used with hepatitis C but not hepatitis B.

Question 23

Hepatitis C

Clinical Extra-hepatic Manifestations of Hepatitis C

Answer 23

Cryoglobulinemia, IC and lymphoproliferative disorder with associated arthralgias, fatigue, palpable purpura, digital ischemia, renal disease, peripheral neuropathy, CNS vasculitis, hypocomplementemia

Question 24

Hepatitis C

Clinical Extra-hepatic Manifestations of Hepatitis C

MPGN with or without cryoglobulinemia:

Answer 24

Cryoglobulins are immunoglobulins directed against the Fc portion of anti-HCV antibody which defines rheumatoid factor activity.

Question 25

Hepatitis C

Clinical Extra-hepatic Manifestations of Hepatitis C

MPGN with or without cryoglobulinemia:

Answer 25

Laboratory findings: positive rheumatoid factor, hypocomplementemia

Chronic active HCV infection may be associated with B-cell lymphoproliferative diseases, with the most common monoclonal gammopathy being IgM, κ light chain.

Question 26

Hepatitis C

Clinical Extra-hepatic Manifestations of Hepatitis C

MPGN with or without cryoglobulinemia:

Answer 26

Clinical manifestations: asymptomatic hematuria and proteinuria, nephrotic syndrome, slowly progressive CKD, or rapidly progressive GN

EM: cryoglobulins resemble “fingerprint” pattern of fibrils of 30 nm.

Question 27

Clinical Extra-hepatic Manifestations of Hepatitis C

Answer 27

Other HCV-associated renal lesions: MGN (two-third of patients have positive anti-PLA2R antibody, significance unknown), fibrillary/immunotactoid GN, PAN

Question 28

Hepatitis C

Clinical Impact of Hepatitis C

Answer 28

Chronic hepatitis C correlates with the incidence of DM type 2 and adverse outcomes.

Question 29

Hepatitis C

Clinical Impact of Hepatitis C

Answer 29

Successful antiviral therapy against HCV is associated with improved insulin resistance and reduced incidence of new-onset DM type 2.

Question 30

Hepatitis C

Clinical Impact of Hepatitis C

Answer 30

The incidence of ESRD, ischemic stroke, and acute coronary syndrome is reduced among successfully treated HCV patients with DM type 2 in a large prospective cohort from Taiwan.

Question 31

Hepatitis C

Clinical Impact of Hepatitis C

Answer 31

Patients with type 2 DM and insulin resistance with hepatitis C are at increased risk for hepatocellular carcinoma.

Question 32

Hepatitis C

HCV in the dialysis patient:

Answer 32

Prevalence is 8% to 9%.

Seroprevalence of HCV increases with dialysis vintage.

Question 33

Hepatitis C

HCV in the dialysis patient:

Answer 33

HCV-infected hemodialysis patients have decreased quality of life and increased mortality compared to their noninfected counterpart.

Question 34

Hepatitis C

HCV in the dialysis patient:

Answer 34

HCV infection may reduce both patient and allograft survival in the kidney recipient. However, kidney transplantation in HCV infected patients may improve survival compared with remaining on dialysis. The advent of highly effective interferon-free and direct acting antiviral therapy may improve post-transplant outcomes.

Question 35

Hepatitis C

Management

Answer 35

Antiviral therapy is recommended for all patients with chronic HCV infection, except for those with short life expectancies.

Question 36

Hepatitis C

Management

For patients with CrCl > 30 mL/min, no dosage adjustment is needed:

Answer 36

Daclatasvir, fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg), or fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) with (or without for HCV genotype 4) twice-daily dosed dasabuvir (250 mg), simeprevir, or sofosbuvir

Question 37

Hepatitis C

Management

For patients with CrCl < 30 mL/min who do not have cirrhosis, but for whom the urgency to treat (or retreat) is high and renal transplant is not an immediate option:

Answer 37

Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombisasvir (100 mg) with twice-daily dosed dasabuvir (250 mg) (for HCV genotype 1b) or without dasabuvir (for HCV genotype 4) is recommended. NOTE: Recommendation is based on limited data on safety and efficacy.

Question 38

Hepatitis C

Management

Answer 38

For HCV genotype 1a, daily fixed-dose combination of paritaprevir (150 mg)/ ritonavir (100 mg)/ombitasvir (25 mg) plus twice-daily dosed dasabuvir (250 mg) with ribavirin at reduced doses (200 mg thrice weekly to daily) is recommended.

Question 39

Hepatitis C

Management

Answer 39

Due to the risk of hemolysis with advanced CKD patients, ribavirin should not be used in patients with baseline hemoglobin concentration ≤ 10 g/dL. Additionally, ribavirin should be discontinued if the hemoglobin level declines >2 g/dL despite use of erythropoiesis-stimulating agents.

Question 40

Hepatitis C

Management

Answer 40

For patients with HCV genotype 2, 3, 5, or 6 and CrCl < 30 mL/min, PEG-interferon and dose-adjusted ribavirin is recommended if treatment is necessary and transplantation cannot be performed.

Question 41

Hepatitis C

Management

Answer 41

For patients with hepatitis C-related renal disease and cryoglobulinemia: Interferon-based regimens have been shown to reverse proteinuria and nephrotic syndrome, but not necessarily ameliorate azotemia.

Question 42

Hepatitis C

Management

Answer 42

Addition of immunosuppressive therapy (e.g., corticosteroids plus either CYC or rituximab) and/or plasmapheresis (if cryoglobulinemia) should be considered if severe renal involvement and poor response to antiviral therapy alone