Page 958 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPter 68 Immunological Renal Diseases 925

evidence for antiviral treatment in HCV-related kidney disease KeY COnCePtS
is based mostly on IFN-based regimens, which have reported
remission of proteinuria and hematuria and improvement of Infection-Related Nephropathies
renal function. 24,25 There are limited data regarding use of the • Viral: Hepatitis B—membranous nephropathy; hepatitis C—cryoglobu-
newer antiviral agents in HCV-associated glomerulonephritis, but linemic membranoproliferative glomerulonephritis; human immuno-
26
these hold considerable promise. For patients with progressive deficiency virus (HIV)—focal segmental glomerulosclerosis (HIV
renal disease and/or nephrotic-range proteinuria, treatment with nephropathy)
rituximab or pulse intravenous steroids and cyclophosphamide • Bacterial (mainly gram-positive): Nephritogenic streptococcal infections,
may be warranted in conjunction with antiviral therapy. Treatment prosthetic device (shunt) infections, subacute bacterial endocarditis,
chronic deep tissue abscesses—mainly diffuse or focal proliferative
with rituximab and plasma exchange may provide additional glomerulonephritis
benefit in patients with HCV-associated severe cryoglobulinemia
refractory to antiviral therapy. 27,28

Human Immunodeficiency Virus
HIV-associated nephropathy (HIVAN), the first kidney disease or minimally depressed C4 levels, indicating activation of the
to be associated with HIV infection, is a collapsing form of focal alternative complement pathway.
segmental glomerulosclerosis accompanied by associated tubular Proliferative glomerulonephritis with polymorphonuclear
microcysts and interstitial inflammation. It was first described leukocyte and monocyte infiltration, granular immune deposits
in patients with acquired immune deficiency syndrome (AIDS) of IgG and C3, and dome-shaped electron-dense subepithelial
but also is occasionally diagnosed in less advanced cases of HIV deposits (humps) are characteristic. The prognosis is excellent
infection and before acute HIV seroconversion has been identified. in children; with supportive care, almost all will recover. Progres-
HIVAN classically presents with significant proteinuria and rapidly sive renal failure accompanied by severe hypertension appears
progressive kidney disease. HIVAN displays a striking racial to be more common in adults. Kidney biopsy is rarely needed
predilection for black patients, which may indicate the importance in the child but may be warranted if there is an atypical presenta-
of genetic influences. 29 tion or evolution. .
A spectrum of other renal abnormalities have also been The classic childhood form is still seen in developing countries
described in patients with HIV infection, including IgA but is now rare in developed countries. However, there has been
nephropathy, lupus-like glomerulonephritis, postinfectious an increase in the incidence of nonstreptococcal postinfectious
glomerulonephritis, MPGN, MN, cryoglobulinemic glomeru- glomerulonephritis or “infection-related” glomerulonephritis,
lonephritis, fibrillary and immunotactoid glomerulopathy, and which tends to be seen in older patients with multiple comorbidi-
thrombotic microangiopathy. 30,31 Tubulointerstitial changes ties, especially diabetes, HIV infection, and malignancy. These
related to drug toxicity, acute interstitial nephritis, or super- clinical variants are usually related to other infective agents, such
imposed viral, fungal, or mycobacterial infections may also be as Staphylococcus aureus, both methicillin-resistant (MRSA) and
present. methicillin-sensitive S. aureus, and may be characterized by an
The mainstay of treatment of HIVAN is combination anti- IgA-dominant glomerular immune complex deposition.
retroviral therapy (cART) regardless of the CD4 lymphocyte Etiology and pathogenesis. Glomerular injury results from
count. Highly effective modern therapies for HIV have reduced passive glomerular trapping of circulating immune complexes
the frequency of developing HIVAN and have greatly improved composed of nephritogenic bacterial antigens and IgG antibody
the otherwise dismal renal prognosis of HIVAN. This has greatly or by the in situ formation of immune complexes. This is fol-
improved the dismal renal prognosis of HIVAN. The evidence lowed by immune cell recruitment, production of chemical
for initiating cART in other HIV-associated immune complex mediators and cytokines, and local activation of the comple-
glomerular diseases is inconclusive, but use of cART is a rational ment and coagulation cascades that drive an inflammatory
approach. The use of standard immunosuppressive drugs in an response. 1
immunocompromised population is controversial. Current therapeutic strategies rely on culture-guided systemic
antibiotics, especially in older patients, in whom MRSA may be
Bacterial Infections the causative agent. Steroids may be used in selected cases in
Poststreptococcal Glomerulonephritis which crescents and severe interstitial inflammation are present.
Poststreptococcal glomerulonephritis is the best-studied and
classic immune complex–mediated glomerulonephritis. It is the
result of skin or throat infection with nephritogenic strains of IgA Nephropathy
group A streptococci. The latent period between upper respiratory
infection and nephritis is 7–10 days, and 2–4 weeks after skin KeY COnCePtS
infection. Antistreptococcal antibody titers are usually measured
to demonstrate the existence of a preceding streptococcal infection. Immunoglobulin A Nephritis (IgAN)
Antistreptolysin O titers and anti-DNase B titers are the most • Common cause of asymptomatic microscopic hematuria, recurrent
frequently elevated in upper respiratory and skin infections, macroscopic hematuria, and/or low-grade proteinuria
respectively. • Spectrum of disease, including idiopathic IgA nephritis and Henoch-
Poststreptococcal glomerulonephritis is characterized by a Schönlein purpura nephritis; IgA in skin and renal biopsy samples
nephritic syndrome consisting of smoky or rust-colored urine, • Mostly benign prognosis, especially in children
generalized edema, hypertension, and nephritic urine sediment. • Patients with progressive renal insufficiency and/or crescentic glo-
Proteinuria is typically mild. Patients have rising titers of anti- merulonephritis warrant trial of glucocorticoids and/or cytotoxic drug
therapy
streptolysin and depressed C3 levels early in nephritis but normal