Chronic Kidney Disease
Table 1: Renal Disease Diagnosis in HIV Subjects
HIVAN
(9 cases)
9
Immune-complex GN (40 cases)
10 mesangial GN
(7 black and 8 MPGN 2 Caucasian) 5 LL-GN
3 immunotactoid 6 diffuse proliferative GN
4 IgAN 4 membranous GN
ESRD = end-stage renal disease; GN = glomerulonephritis; IgAN = IgA nephropathy; LL-GN = lupus-like glomerulonephritis; MPGN = membranoproliferative glomerulonephritis; NC-FSGS = non-collapsing focal segmental glomerulosclerosis.
Figure 1: Subendothelial, Subepithelial and Mesangial Electron-dense Deposits Observed in a Glomerulus from HIV-associated Immune-complex Glomerulonephritis
3 minimal change 3 ESRD
4 diabetic nephropathy 1 amyloidosis
syndrome with microscopic haematuria, hypertension and frequent renal insufficiency; the prognosis is worse than non-HIV cases.
Non-immune-complex GN (24 cases)
13 NC-FSGS
Hepatitis C co-infection is frequent in this group, without clinical or serological manifestations of cryoglobulinaemic glomerulonephritis. According to some authors, hepatitis C/HIV co-infection seems to worsen clinical manifestations of immunotactoid glomerulonephritis.46 This observation is not supported by other studies, in which the authors do not find a difference between cases with hepatitis C/HIV co-infection compared with cases with HIV alone.39
IgAN has a prevalence ranging between 4 and 10% of HIV cases with renal disease. IgAN is found less frequently in subjects of African descent than in the white or Hispanic population. Cases of IgAN in HIV subjects have probably been underestimated in the past because of the paucity of clinical manifestations resulting in low indication for renal biopsy; for this reason, IgAN is more frequent in autopsy series.47
The histological pattern is similar to that encountered in non-HIV patients, although some peculiar features have been observed, such as a tendency to multiple site localisation of deposits and the presence of other immunoglobulins (i.e. IgG and IgM) besides IgA.33 Moreover, a rapid tendency to sclerotic evolution of histological lesions has been observed; this is in agreement with the general fibrogenic upregulation found in HIV-positive subjects.48,49
Original magnification x3,000.
HIV-related post-infectious diffuse proliferative glomerulonephritis, unlike non-HIV cases, has a prolonged atypical clinical course, with a lower recovery rate (30–60% of cases in different series). Urinary signs can persist for months and there is more probable evolution of CKD.41 According to different series, Streptococcal infection is the causative agent in 17–40% of cases and Staphylococcal infection in 12–25% of cases, while in 24–58% of cases no infection is revealed.42
Fibrillary immunotactoid glomerulonephritis is rare, occuring in 2–4% of patients.43
Diagnosis is made by electron microscopy. In HIV-positive
subjects, immunotactoid glomerulonephritis is more frequent than fibrillary glomerulonephritis. This is in agreement with the observation that the former is more closely related to systemic or infectious disorders, while the latter is more often ‘idiopathic’.44
Immunotactoid glomerulonephritis is differentiated from fibrillary glomerulonephritis by fibril diameter, space orientation of deposits and overall ultrastructural appearance. Immunotactoid glomerulo- nephritis is characterised by the presence of microtubular structures, with 30–50nm diameter and a hollow centre. The microtubular structures are distributed in parallel arrays and are mainly located on the subepithelial side of the basal membrane.
Fibrillary
glomerulonephritis has smaller fibrils (18–22nm diameter), which are randomly distributed and have an appearance closely resembling amyloid fibrils.45
The clinical picture is characterised by nephrotic
22
The prevailing clinical pictures in IgAN are proteinuria and microscopic haematuria. It does not differ from non-HIV cases, except for the evolution to end-stage renal disease, which is more rapid in HIV subjects. Serum IgA increase is frequent and IgA immune complexes directed to HIV antigens have been detected; IgA antibodies against anti-gp41, p24 IgG and IgM have been found, with IgA bearing rheumatoid factor activity.50
Membranous glomerulonephritis in HIV patients is slightly more frequent than IgAN and presents equally in various ethnic groups. The histological pattern is similar to non-HIV cases and has no peculiarities, except for the presence of tubulo-reticular inclusions in endothelial cell cytoplasm observed by electron microscopy. Some authors describe an increase of basal membrane sclerosis and a few mesangial deposits associated with the classic subepithelial pattern.33
Clinical features are characterised by a prevalent nephrotic syndrome and more rapid evolution of renal insufficiency in comparison with non-HIV cases.
Glomerulopathies Not Related to Immune-complex Glomerulonephritis
This group includes heterogeneous histological lesions, non-HIVAN and non-immune-complex glomerulonephritis, among which non-collapsing FSGS (NC-FSGS) is prominent, accounting for about 15% of all HIV-related glomerulopathies.1,33
Other, rarer varieties include minimal change disease, amyloidosis, diabetic nephropathy and nephrosclerosis.
The main lesion is focal and has segmental tuft sclerosis with capsular adhesions but without collapse of the glomerular tuft. Hyaline deposits within sclerosis are rarely seen. Tubulointerstitial fibrosis frequently accompanies the glomerular
NC-FSGS is morphologically classifiable within the ‘not otherwise specified’ FSGS variant according to the Columbia Pathology Group classification.26
EUROPEAN NEPHROLOGY
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