Geriatric Nephrology


Figure 1: Proposed Etiology of Pauci-immune Glomerulonephritis


E. coli, Klebisella, Proteus FimH Epi Minimal Change Disease Ab cross-reactive with LAMP-2


Glomerular endothelial cell


Anti-MPO or PR-3 MPO and PR-3


During infection with fimbriated bacteria (e.g. Escherichia coli, Klebsiella, Proteus), the bacteria bind to epithelial (Epi) cells and antibody (Ab) is produced that recognizes the bacterial protein, FimH. Through molecular mimicry, this antibody recognises and binds to LAMP-2 in endothelial cells, causing apoptosis.22


Antibodies to LAMP-2 also activate neutrophils, which can lead to release of myeloperoxidase (MPO) and proteinase-3 (PR-3). Antibodies to MPO and PR-3 are detected as anti-neutrophil cytoplasmic antibodies (ANCA). Both ANCA and anti-LAMP-2 antibodies can bind to glomerular endothelial cells and initiate a necrotizing form of glomerulonephritis (GN). Because few of these antibodies actually remain deposited in the glomerulus, this form of GN is known as pauci-immune.


Necrotising GN


Their response to treatment is similar to younger age groups; thus, they should be treated. Risk for development of diabetes and infection with immunosuppressive treatment is somewhat greater in elderly than in younger individuals, yet untreated individuals of all ages with severe nephrotic syndrome have a high rate of infection- associated death. Among adults with nephrotic syndrome, MCD disease occurs more often in the elderly than in younger adults, and in this age group it is often misdiagnosed as congestive heart failure. Recent attempts to treat refractory cases of this disorder with antibodies to interleukin-2 receptor or B cells have shown some promise,16,17 results in elderly individuals have not been reported.


yet


Post-infectious Glomerulonephritis The most common organism associated with acute proliferative glomerulonephritis (PIGN) is Group A streptococcus. This entity is uncommon in adults and, in general, its incidence is declining in the developed world. A recent review14


of 86 cases showed a mean age of


56 years with 34% being over 64 years of age. Unlike PIGN occurrence in children, as many as 38% of older adults with PIGN had an underlying disorder associated with immunocompromise. Complete remission occurred in slightly more than half of these subjects, and was less likely in those with pre-existing kidney disease or illnesses associated with immunocompromise. Among individuals with pre-existing diabetic glomerulosclerosis, remission was rare and rapid progression to ESKD often followed. Thus, outcomes appear to be worse in elderly persons as a result of their greater likelihood of having another condition that has led to immunocompromise and/or altered kidney function. No studies address the incidence or outcomes in older individuals with PIGN due to organisms other than Group A streptococcus. Given the frequency of pneumococcal pneumonia and other infections in elderly individuals, infections that are less often associated with PIGN in younger individuals may contribute in higher proportions in elderly persons.


Lupus Nephritis


Lupus is generally a disease of women of childbearing age, yet 10–20% of cases occur in older individuals, including those over 65 years of age. When lupus develops in older individuals, the spectrum of manifestations differs somewhat from that seen in younger individuals. Arthritis, fever, serositis, sicca symptoms, Raynaud’s syndrome, lung disease, and neuropsychiatric symptoms are more common in elderly


94


Focal and Segmental Glomerulosclerosis Current evidence shows that the pathologic pattern that defines FSGS can be observed in a heterogeneous group of diseases. The idiopathic form of FSGS typically presents with proteinuria and reduced GFR in young adults, and it is likely due to a variety of gene mutations. This form of FSGS is relatively uncommon in elderly persons (see Table 1), and when it occurs it is not thought to result from pre-existing gene mutations. Focal areas of scarring can occur with vascular disease, hypertension, or in aging nephropathy, where it is postulated to reflect cellular senescence; however, detailed studies have not been conducted in elderly persons.


Membranous Nephropathy


In adults of all ages, MN is the most common cause of nephrotic syndrome; however, the incidence is greatest in individuals 40–60 years of age. Because multiple myeloma and amyloidosis make up 15–20% of nephrotic syndrome in older individuals, MN accounts for only 15% of elderly individuals with nephrotic syndrome. In a recent landmark study, Beck and colleagues19


reported compelling evidence of an autoimmune,


antibody-mediated basis for a majority of cases of idiopathic MN. Circulating antibodies to the phospholipase A2 receptor (PLA2R), a protein expressed on the surface of the podocyte, were found bound in the glomerulus of biopsies from subjects with MN. Seventy percent of MN subjects, and none with membranous lupus nephritis, had these antibodies, suggesting that the etiology of the two forms of MN differ. The PLA2R is a transmembrane protein of the mannose receptor family that binds PLA2. Currently, nothing is known about the role of PLA2R activation in mediating podocyte injury or the mechanism that leads to development of these auto-antibodies in MN. Only one individual in that study was over 75 years of age; thus, additional studies are needed to confirm the relevance of this particular auto-antibody to MN in elderly individuals. Although the incidence of cancer increases with age, and cancer and MN are sometimes present in the same individual, there is no evidence that MN and cancer are directly linked in elderly persons other than by coincidence.


US NEPHROLOGY


As many as 15–20% of older individuals with nephrotic syndrome will have MCD.7,9


persons, whereas malar rash, discoid lupus, and GN are less common. GN may be less common because anti-DNA antibodies are rare, even though antinuclear antibodies (ANA), anti-Ro, and anti-La are commonly detected. When lupus—with or without nephritis—occurs in elderly individuals, diagnosis is often delayed; however, when lupus nephritis is present, it should be treated the same as in younger subjects.15


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