Viral Nephritides Flashcards
Viral Nephritides
HIV
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.
Viral Nephritides
HIV-Associated Nephropathy
Predominantly observed in African American
Associated with advanced HIV (i.e., CD4 < 200 cells/mm3, high viral load)
Viral Nephritides
Epidemiology
Clinical Manifestations
Nephrotic range proteinuria, hematuria, normal to enlarged kidneys due to microcyst formation
Viral Nephritides
Pathogenesis
Genetic susceptibility: APOL1
Both direct and indirect mechanisms involving HIV are thought to be contributory.
Viral Nephritides
Histopathology
LM: collapsing FSGS, tubular microcystic dilatation with proteinaceous casts, and variable acute tubular injury, tubular atrophy, lymphocytic infiltrates, interstitial fibrosis
Viral Nephritides
Histopathology
EM: presence of tubuloreticular inclusions in endothelial cell cytoplasm in untreated patients
Viral Nephritides
Natural History/Prognosis
Rapid progression to ESRD if untreated
Viral Nephritides
Management
Combined antiretroviral therapy (cART), renin–angiotensin system inhibition, corticosteroid therapy if rapid decline in kidney function despite cART and absence of superimposed/opportunistic infections
Viral Nephritides
HIV-Associated Immune Complex Kidney Disease
Background
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.
Viral Nephritides
HIV-Associated Immune Complex Kidney Disease
Clinical Manifestations
Nephrotic syndrome, hematuria, HTN; Laboratory findings may be positive for ANA, low C3
Viral Nephritides
HIV-Associated Immune Complex Kidney Disease
Histopathology
IF: notable for variable Ig/complement staining, “full house” of Ig may be present
EM: presence of cytoplasmic tubuloreticular structures in endothelial cells
Viral Nephritides
Combined Anti-retroviral Treatment (cART) Nephropathy
Nucleotide analog reverse transcriptase inhibitors: mitochondrial dysfunction, Fanconi syndrome, AKI/ATN:
Most well-recognized: tenofovir
Others: lamivudine (3TC), abacavir (ABC), didanosine (ddI)
Viral Nephritides
Combined Anti-retroviral Treatment (cART) Nephropathy
NOTE: mitochondrial injury may be seen on EM as giant mitochondria with atypical shapes and broken or absent cristae.
Viral Nephritides
Combined Anti-retroviral Treatment (cART)
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”
Thrombotic Microangiopathy
May be seen with advanced HIV, not treated with cART
Pathogenesis thought to involve direct HIV attack of endothelial cells
Thrombotic Microangiopathy
Affected individuals may have low ADAMTS13 levels, in which case, good response to therapy including corticosteroids and plasma exchange may be expected.
Kidney Transplantation in Patients with HIV
May be considered if undetectable viral load and CD4 > 200 cells/mm3
Requirement for immunosuppressive therapy is typically minimal due to drug-drug interactions.
Kidney Transplantation in Patients with HIV
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.
Hepatitis B
Associated Lesions
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)
Hepatitis B
Management
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.
Hepatitis B
Management
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
Hepatitis B
Management
Do not use rituximab due to association with hepatitis B reactivation. Rituximab may be used with hepatitis C but not hepatitis B.
Hepatitis C
Clinical Extra-hepatic Manifestations of Hepatitis C
Cryoglobulinemia, IC and lymphoproliferative disorder with associated arthralgias, fatigue, palpable purpura, digital ischemia, renal disease, peripheral neuropathy, CNS vasculitis, hypocomplementemia
Hepatitis C
Clinical Extra-hepatic Manifestations of Hepatitis C
MPGN with or without cryoglobulinemia:
Cryoglobulins are immunoglobulins directed against the Fc portion of anti-HCV antibody which defines rheumatoid factor activity.
Hepatitis C
Clinical Extra-hepatic Manifestations of Hepatitis C
MPGN with or without cryoglobulinemia:
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.
Hepatitis C
Clinical Extra-hepatic Manifestations of Hepatitis C
MPGN with or without cryoglobulinemia:
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.
Clinical Extra-hepatic Manifestations of Hepatitis C
Other HCV-associated renal lesions: MGN (two-third of patients have positive anti-PLA2R antibody, significance unknown), fibrillary/immunotactoid GN, PAN
Hepatitis C
Clinical Impact of Hepatitis C
Chronic hepatitis C correlates with the incidence of DM type 2 and adverse outcomes.
Hepatitis C
Clinical Impact of Hepatitis C
Successful antiviral therapy against HCV is associated with improved insulin resistance and reduced incidence of new-onset DM type 2.
Hepatitis C
Clinical Impact of Hepatitis C
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.
Hepatitis C
Clinical Impact of Hepatitis C
Patients with type 2 DM and insulin resistance with hepatitis C are at increased risk for hepatocellular carcinoma.
Hepatitis C
HCV in the dialysis patient:
Prevalence is 8% to 9%.
Seroprevalence of HCV increases with dialysis vintage.
Hepatitis C
HCV in the dialysis patient:
HCV-infected hemodialysis patients have decreased quality of life and increased mortality compared to their noninfected counterpart.
Hepatitis C
HCV in the dialysis patient:
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.
Hepatitis C
Management
Antiviral therapy is recommended for all patients with chronic HCV infection, except for those with short life expectancies.
Hepatitis C
Management
For patients with CrCl > 30 mL/min, no dosage adjustment is needed:
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
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:
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.
Hepatitis C
Management
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.
Hepatitis C
Management
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.
Hepatitis C
Management
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.
Hepatitis C
Management
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.
Hepatitis C
Management
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
