Saudi Journal of Kidney Diseases and Transplantation

: 1994  |  Volume : 5  |  Issue : 1  |  Page : 6--11

Monitoring of Glomerulonephritis

E Nigel Wardle 
 Oxford 0X8 6RD England, United Kingdom

Correspondence Address:
E Nigel Wardle
MRCP 21 Common Road, North Leigh, Oxon 0X8 6RD, England
United Kingdom


In addition to the standard biochemical measures we need better methods for monitoring of glomerulonephritides. A variety of new tests are now available. One has to be selective in one«SQ»s choice. Attention has to be paid to means of assessing interstitial fibrosis and damage to the tubules of the kidneys.

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Wardle E N. Monitoring of Glomerulonephritis.Saudi J Kidney Dis Transpl 1994;5:6-11

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Wardle E N. Monitoring of Glomerulonephritis. Saudi J Kidney Dis Transpl [serial online] 1994 [cited 2021 May 15 ];5:6-11
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Although we all measure serum creatinine and 24-hour urine protein excretion values, one should be aware that there are now better refined methods for the monitoring of individual cases of glomerulonephritis (GN). When we look at the list of possibilities, we have to judge what we would like to have in relation to the work load and technical capability of one's laboratory service. [Table 1] lists the currently available techniques [1],[2],[3],[4],[5],[6],[7],[8],[9],10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33] . Nobody would consider doing all these tests on their nephritis patients. Rather, one will select those tests that are most advantageous for monitoring the particular forms of nephritis that one has to deal with. Therefore the approach that I will use is correlation of the appropriate tests with each clinical form of nephritis.

 Minimal Change Idiopathic Nephrotic Syndrome

We see many children with minimal change idiopathic nephrotic syndrome (INS). Often the cause of this nephrotic syndrome is not known, but one should seek diligently for possible allergy to different forms of milk (cow, goat or camel), to eggs or even to pollens [34] . Hence it could be useful to use an elemental diet with gradual reintroduction of foods. In INS, a urine protein selectivity index of less than 0.2 will indicate responsiveness to corticosteroids. A non-selective index of more than 0.2 could indicate that the biopsy will show focal glomerulosclerosis (FGS). Mean-time measurement of serum interleukin (IL)-2 receptors will give an indication of disease activity [23] , as also will measure-ment of Fc €RII on B cells [25] , preferably using flow cytometry. It has been found that raised serum IgE levels and Fc €RII on B cells of such patients correlates with production of IL-4 by Th-2 like lymphocytes, i.e. lymphocytes that are primed for allergic antibody production. Unfortunately in tropical countries helminthes evoke similar responses. More research around this topic is required. Is it genetic or environmental predisposition to a Th-2 like response that predisposes to INS? Does that also apply in adults? Certainly we know that T cells of such patients are producing a permeability proteinuric lymphokine, that may be tumor necrosis factor (TNF) like [35] . We also know that in the active phase, the mononuclear cells of such patients are producing IL-1 and IL-2 [29] .

 Acute Post-Streptococcal Glomerulonephritis (APSGN)

These cases are common in the Middle East. 7-10 days after a Streptococcal sore throat, formation of circulating immune complexes and their subsequent deposition in the glomerular filters leads to an acute proliferative GN [36] . Within the first week of active nephritis the platelet counts are lowered [13] , platelet turnover is increased and platelet factor (PF)-4 can be shown to be localized in the glomeruli [37] . Complement levels are typically lowered in ASPGN, mesangiocapillary GN, Systemic Lupus Erythematosus (SLE) glomerulonephritis and with the nephritis that accompanies endocarditis [4] . When there is only alternative pathway of complement activation, only C3 component is low. Normally in ASPGN, both C3 and C4 are lowered on account of alternative and classical pathway activation. One is always concerned that some cases of APSGN will progress to the nephrotic syndrome or to chronic renal failure with glomerulosclerosis. If it is present one may wish to identify "nephritic factor" at the early stage and may be to look for other forms of activated complement like iC3b, C3a des Arg, C5a or the C5b-9 complex [38] .

In the acute phase of APSGN radiofibrinogen catabolism will be increased, as a reflection of fibrin deposition in the renal glomeruli [17] . However, it should then become near-normal. An abnormal increase of turnover will persist in those cases with on-going glomerular damage [39] . Unfortunately this is a technique that is only taught in special centers. [Figure 1] indicates the form of graph of the plot of daily plasma labelled fibrinogen counts. In this case the patient had endocarditis causing acute proliferative GN [40] . One will note that the whole process was improved after the onset of heparin infusion.

 Systemic Lupus Nephritis

In this field, the new information is that one can measure the level of soluble TNF receptors (p55 or p75) by ELISA as an indicator of disease activity [26] . Alternatively, one can quantitate serum interferon (IFN)-y which correlates with the expression of major histocompatibility complex MHC class II antigens in the glomeruli and with their proliferation [27] . Yet one might have the same result by measuring serum IL-2 receptor values [27] . Also it has been shown that urinary IL-6 values, as measured by growth of an IL-6 dependent hybridoma MH60; BSF2, correlate with levels of anti- DNA antibody [30] . Furthermore, effective treatment lowers the excretion of IL-6.

 Glomerulonephritis Associated with Vasculitis

One has to recognize that many cases of vasculitis are drug induced. Penicillamine, hydrallazine, the thiazides, even frusemide and many other drugs can cause vasculitis with associated glomerulonephritis. Measurement of anti-neutrophil cytoplasmic antibody (ANCA) and characterization of its target antigen has now become the standard approach to differentiating polyarteritis with glomerulonephritis from Wegener's syndrome [11],[12] . The perinuclear pANCA is caused by antibodies to antigens that are drawn toward the nucleus of neutrophils during fixation. Those antigens include myeloperoxidase elastase and lactoferrin. The pANCA is positive in cases of microscopic polyarteritis. Conversely a cytoplasmic cANCA is commonly caused by antibodies to serine protease 3 of the azurophilic granules and that occurs in Wegener's syndrome. Since all these antigens are cationic, they are ideal for the induction of glomerulonephritis. A fall of ANCA titre does indicate successful treatment of these syndromes. Conversely a rise of titre will often indicate the need for a new form of therapy [41] .

One must also bear in mind that idiopathic crescentic nephritis is often associated with antibodies to the leucocyte lysosomal enzymes [42] . In fact an anti-myeloperoxidase ANCA can be an indicator of cellular crescents. Accumulation of neutrophils in the lungs during infection can release myeloperoxidase (MPO) that is an antigen that can cause proliferative nephritis [43] .

 IgA Nephropathy

Advances in this field are needed. This is the commonest nephritis in the world and we do not know its cause, although a respiratory tract virus might be suspected. Typically patients have recurrent sore throats and accompanying hematuria. In adults there may simply be progressive renal failure. Measurement of urinary red cell excretion and other means of monitoring are desirable. As is the case with SLE, increased urinary excretion of IL-6 has been claimed [31] . Some groups do not find this, but their technique or type of case may differ. Measurement of serum IFN-y could be better. As in SLE nephritis, the serum IFN-y relates to (MHC) class II antigens present in the glomeruli and thus to the local immune reaction [28] . In fact Ballardie and co-workers have related an increased percentage of blood monocytes expressing MHC class II antigens to disease activity [44] . Mononuclear cells of those patients show increased production of cytokines like Transforming Growth Factor TGF β .

There might be other approaches. Thus TGF β in urine could give an assessment of the glomerular sclerosing process [32] . Nakamura et al have shown that the monocytes of IgA nephropathy patients produce messenger RNA for the endothelin 1 and that the amount is increased according to the degree of proteinuria and histological grade of nephritis. One has to extract the RNA of mononuclear cells and then to use in situ hybridization using cDNA probes, specifically one for endothelin-1 [32] . A similar form of analysis can be used to quantitate platelet derived growth factor (PDGF)- β chain that is produced by blood mononuclear (non T) cells. Total RNA extracts from the peripheral blood mononuclear cells are spotted on a nylon filter and then there is hybridization of the spots with a cDNA probe for PDGF-β chain [33] . These findings must reflect the degree of monocytemacrophage activation in the glomeruli of IgA nephritis and accordingly the production of growth factors like PDGF-β .

There is not only sclerosis of the glomeruli but interstitial fibrosis in the medulla of the kidneys and damage to tubules. Hence an assay using SDS-PAGE for detection and quantitation of low molecular weight proteins in the urine can be useful [45] .

 Detecting and Monitoring Renal Interstitial Damage

For some time we have been aware that macrophage activity in inflammed glomeruli leads on to proliferative responses and ultimately glomerulosclerosis [46] . In all the glomerulonephritides a similar process may be taking place in the medulla of the kidneys [47],[48] . This means that, we have to add tests for proximal and distal tubule function to our investigations of conditions like membranous nephropathy [49] , which may or may not result in progressive renal disease. Therefore, we will be interested in techniques such as the urinary excretion of p2 microglobulin and urinary retinol binding protein [50] .


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