HIV + virus

Question 1

HIV

Answer 1

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, TMA.

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

Predominantly observed in African American

Genetic susceptibility: APOL1

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

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

risk factors for CKD in HIV are : age, race, CKD family history, HIV disease state(CD4 count, HIV viral load), History of cocaine use, cigarette use, nephrotoxic medication use and comorbid conditions like Diabetes, HTN and Hep C co infection.

Question 2

hiv

Histopathology

Answer 2

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

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

apagamento dos processos podocitarios

agregados tubuloreticulares nas cels endoteliais

AUSENCIA de complexos imunes

colapsante= colapso do tufo segmentar ou global + proliferacao visceral celular adjacente

dilatacao microcistica tubular com inflamacao tubulointersticial adjacente

Question 3

Viral Nephritides

Natural History/Prognosis

Answer 3

Rapid progression to ESRD if untreated

Question 4

Viral Nephritides

Management

Answer 4

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 5

Viral Nephritides

HIV-Associated Immune Complex Kidney Disease

Background

Answer 5

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 6

Viral Nephritides

HIV-Associated Immune Complex Kidney Disease

Clinical Manifestations

Answer 6

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

Question 7

Viral Nephritides

HIV-Associated Immune Complex Kidney Disease

Histopathology

Answer 7

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

EM: presence of cytoplasmic tubuloreticular structures in endothelial cells

Question 8

Viral Nephritides

Combined Anti-retroviral Treatment (cART) Nephropathy

Answer 8

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

Most well-recognized: tenofovir

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

Question 9

Viral Nephritides

Combined Anti-retroviral Treatment (cART) Nephropathy

Answer 9

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

Question 10

Viral Nephritides

Combined Anti-retroviral Treatment (cART)

Answer 10

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 11

Thrombotic Microangiopathy

Answer 11

May be seen with advanced HIV, not treated with cART

Pathogenesis thought to involve direct HIV attack of endothelial cells

Question 12

Thrombotic Microangiopathy

Answer 12

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

Question 13

Kidney Transplantation in Patients with HIV

Answer 13

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 14

Kidney Transplantation in Patients with HIV

Answer 14

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 15

Hepatitis B

Associated Lesions

Answer 15

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 16

Hepatitis B

Management

Answer 16

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 17

Hepatitis B

Management

Answer 17

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 18

Hepatitis B

Management

Answer 18

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

Question 19

Hepatitis C

Clinical Extra-hepatic Manifestations of Hepatitis C

Answer 19

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

Question 20

Hepatitis C

Clinical Extra-hepatic Manifestations of Hepatitis C

MPGN with or without cryoglobulinemia:

Answer 20

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

Question 21

Hepatitis C

Clinical Extra-hepatic Manifestations of Hepatitis C

MPGN with or without cryoglobulinemia:

Answer 21

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 22

Hepatitis C

Clinical Extra-hepatic Manifestations of Hepatitis C

MPGN with or without cryoglobulinemia:

Answer 22

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 23

Clinical Extra-hepatic Manifestations of Hepatitis C

Answer 23

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

Question 24

Hepatitis C

Clinical Impact of Hepatitis C

Answer 24

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

Question 25

Hepatitis C

Clinical Impact of Hepatitis C

Answer 25

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

Question 26

Hepatitis C

Clinical Impact of Hepatitis C

Answer 26

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 27

Hepatitis C

Clinical Impact of Hepatitis C

Answer 27

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

Question 28

Hepatitis C

HCV in the dialysis patient:

Answer 28

Prevalence is 8% to 9%.

Seroprevalence of HCV increases with dialysis vintage.

Question 29

Hepatitis C

HCV in the dialysis patient:

Answer 29

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

Question 30

Hepatitis C

HCV in the dialysis patient:

Answer 30

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 31

Hepatitis C

Management

Answer 31

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

Question 32

Hepatitis C

Management

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

Answer 32

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 33

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 33

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 34

Hepatitis C

Management

Answer 34

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 35

Hepatitis C

Management

Answer 35

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 36

Hepatitis C

Management

Answer 36

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 37

Hepatitis C

Management

Answer 37

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 38

Hepatitis C

Management

Answer 38

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