The Music of Glomerulonephritis

This is a lecture about Glomerulonephritis that can be delivered - if you want - with music. Glomerulonephritis can be an intimidating subject, but it shouldn't be. It's interesting! And to make it simple, there are 3+2 causes of most things (with a bit of cheating). All is related to a simple diagram that shows the principles of glomerular injury. See the content list at the left.

This lecture forms part of half a day of renal teaching in Year 4 of the Edinburgh undergraduate curriculum in Medicine. It comes just after 20 minutes on The Presentation of Renal Diseases, and is followed by 20 minutes on Interstitial and Tubular diseases. See the whole programme [link to follow]. The knowledge in this lecture should be more than enough to pass any written undergraduate assessment on glomerulonephritis. Or you have crazy examiners. Postgraduates will want a bit more, but might still like to start here.

Normal glomerulus

Here is a normal glomerulus. It sits in loops of proximal and distal tubules, and at 6 o'clock it comes into close contact with its own distal tubule at the macula densa.

The title of this talk mentions "glomerulonephritis", literally inflammation of glomeruli, but it should really be "glomerulopathy", as it is going to include non-inflammatory diseases, or barely inflammatory diseases, because the consequences are the same.

Nephron

The glomerulus sits at the end of a nephron, , and in each kidney approximately 1 million of these contribute to the daily glomerular filtrate of about 150 litres, that's 30 Imperial gallons (40 US gallons) and double your weight, or a good bathful. [Beth’s pic here]

The tubules reabsorb 99% of this, so quite small alterations in the proportion of, say, sodium or water that is reabsorbed will quickly affect overall balance.

Creatinine and size - rather oddly

[Improve this fig and add more about GFR?]

But the most informative figure for overall renal function is the glomerular filtration rate, GFR, which should be about 100 mls/minute in an average sized person.

Normal glomerulus

See how there is a lot of white space in this normal glomerulus. In life these are capillary loops, which are filled with blood. The glomerular basement membrane, or GBM around these loops should look sharp - "as if you could cut your finger with on them".

Cells of the glomerulus

In this diagram you can see how podocytes sit outside these capillary loops, holding them open and synthesizing most of the GBM. We'll look at them more closely shortly.

Inside the loops, endothelial cells are smeared very thinly around with only the nuclei really visible.

A few mesangial cells sit in between the loops

Normal glomerulus

The pink material in the middle, between the capillary loops, is mesangial matrix, synthesized by mesangial cells. You shouldn't see more than three mesangial cells together.

Podocytes can be seen at the edges. Endothelial cells - you can just see their nuclei.

GN causes: Text slide

So what happens when this goes wrong?

Glomeruli leak things that should normally remain in the blood, protein and even blood cells

High blood pressure is a prominent feature of most but not all types of glomerulonephritis.

And you lose filtration capacity, GFR.

It is important because

Glomerulonephritis is important because it is a common cause of end stage renal failure, and because much of it is treatable or preventable.

So taking the things it does one by one ...

Changes in urine (text) -

Sometimes a gross leak gives rise to changes the patient can see -

pic of colours etc

frothy urine can be caused by proteinuria, and sometimes enough blood leaks to be visible. There are other possible causes of these appearances of course.

pic of volumes

Changes in urine volume, which is mostly controlled by tubules, are not very helpful, except that in very aggressive or very late disease, GFR falls low enough for urine volumes to be reduced.

Dipstick

But most of the time, the information comes from urine testing. We'll take the findings one at a time.

Proteinuria - text … tubule etc diag

The glomerular filter is quite porous, in that it's only when you get up to molecular weights of 60,000 or so that the barrier is nearly complete. Below 20,000 there is free filtration, so many short peptides, including many hormones such as insulin and other small proteins, are normally filtered. Between 20 and 60,000 there is a gradient of progressively less filtration. These filtered proteins are normally taken up from the filtrate in the proximal tubule and metabolised in proximal tubular cells. The small amount of protein normally found in urine is most Tamm Horsfall protein which is secreted further down the tubule.

Tubular diseases that upset the mechanism for the reabsorption of protein can lead to tubular proteinuria, when low molecular weight proteins appear in the urine, but this does not normally amount to more than a maximum of a couple of grams of protein per day. Beta-2 microglobulin appearing in the urine would be a sign of this. Immunoglobulin light chains are mentioned here because if free light chains are overproduced, as happens in some B lymphocyte disorders, they will be freely filtered, and some of these chains may precipitate and/or be toxic to tubules, causing myeloma kidney for example.

Albumin is a very useful marker, because there are huge quantities of it in plasma, and the tiny quantities that get filtered at a normal glomerulus (it has a molecular weight of 67,000) are easily reabsorbed by the usual tubular mechanism. However this mechanism can be quickly overloaded if there is a glomerular protein leak.

Barrier - Wartiovaara

Let's take a closer look at the glomerular filtration barrier by electron microscopy. A shows an enlarged view of a segment of a glomerular capillary wall, with the capillary lumen below. E is for endothelial cell, which has pores known as fenestrae in it, and FP are the cut-across, complex foot processes of podocytes. C shows the gap between two adjacent foot processes at higher magnification to show the

slit diaphragm

You can see a faint structure in the middle which is magnified further in D. Pores between these strands are almost exactly the size of an albumin molecule. The strands are made up nephrin, and when this protein is mutated or absent, there is a catastrophically severe protein leak, a condition known as Finnish congenital nephrotic syndrome. It is so severe that affected babies sometimes have nephrectomies to control it, meaning of cause that they have to be dialysed from infancy.

EM from

Here, the lower panel shows a normal rat glomerular capillary, endothelial side below, urinary side above. The upper panel shows a similar view a few hours after injection of a monoclonal antibody that disrupts the slit diaphragm. The animal develops proteinuria within minutes, and this is associated with the loss of morphology of the foot processes.

[PAUSE PLAY]

This and other pieces of evidence suggest that the slit diaphragm is the site of the glomerular barrier to protein, and not the GBM itself, which is a more open network like a big sponge.

Glomerular proteinuria

So to summarize, Albumin is the hallmark of glomerular proteinuria

There are some circumstances in which it is a transient phenomenon, but if persistent it implies significant glomerular disease.

Microalbuminuria

Using very specific and sensitive assays, albumin can be detected in urine before it reaches levels that increase total urinary protein. This provides early warning of glomerular disease, and has proved very useful for instance in early diabetic nephropathy. However microalbuminuria is also found in patients with extensive vascular disease, as in atherosclerosis. The mechanism is not clear, but it is important because there is a strong association between even these very low levels of albuminuria and increased cardiac risk, even if GFR is normal.

Proteinuria: quantitative

Quantitation of proteinuria is the other useful differentiating feature. Although traditionally done by measuring protein in a 24 hour collection, it is best done by measuring protein/creatinine ratio in single samples. 100mg/mmol is approximately equivalent to a daily protein excretion of 1 gram.

Black

Next haematuria, and it has different music

Daigrammatic glomerulus

Unlike proteinuria, haematuria can come from anywhere in the urinary tract, and indeed more commonly comes from below the kidney. However here we're looking at how blood gets from the glomerular capillary into the urinary space. Red cells are big, so the GBM has to be broken. (Two examples of how this can happen.)

First example Alport

On the left is a segment of a normal glomerular capillary wall, capillary below, urinary spaceabove, GBM the grey line from Left to Right. One the right is a similar view from a patient with Alport syndrome, in which one of the three specialised type IV collagen chains that make up the GBM is mutated. The GBM degenerates, causing renal failure that comes on in teens or twenties, typically associated with progressive deafness as similar changes occur in the cochlea. This is usually an X-linked recessive disease so the disease is most common in young men. Not surprisingly, haematuria is a feature. Alport syndrome is the second most common inherited cause of renal failure , after polycystic kidney disease.

Bonsib

And here is an acquired mechanism. On the left we're looking down on a rat glomerulus from which Bowman's capsule and all the podocytes that would usually cover the GBM have been removed. On the right, the same view after the GBM has been attacked by an immune response generated by anti-GBM antibodies. You can see that holes have been blown in the capillary walls allowing blood cells and components to escape into Bowman's space.

Reider 1898 pic of red cell casts

As the red cells pass down the nephron, they may form red cell casts which will appear in urine like this.

Collar 2001 EM of rbc squeezing through a gap

Most holes are more subtle than the ones you just saw, and as the cells are squeezed through cracks the take a bit of a beating.

Glom rbc Fogazzi

This can be useful diagnostically, as the fragments and misshapen cells on the right show, but the requirement for high quality microscopes and skilled operators have prevented the widespread adoption of this as a quick diagnostic technique.

We've touched on proteinuria and haematuria, which leaves fluid and function, and we're just going to touch on each of those.

BP and fluid - pic of salt

Extracellular fluid balance is essentaillly a question of salt management. Salt retention and high blood pressure are disturbed very early in many glomerular diseases, but of course they become a problem in all types of kidney disease when GFR drops low enough.

Intravasc fluid

The first sign of excess intravascular fluid, if you have a normal heart, is hypertension. More extreme fluid retention leads to high right atrial pressure, which you assess as jugular venous pressure, then to high left atrial pressure and pulmonary oedema. This of course looks very like heart failure. Be very suspicious of heart failure with high blood pressure - look for a renal contribution. However it is very common for cardiac and renal disease to coexist.

Extravasc fluid

Peripheral fluid collects if sodium retention and volume overload continue, though an average person can accumulate some litres of excess extracellular fluid before this develops. In adults we classically see this at ankles first. Children and young adults may develop ascites before ankle oedema though - as will those with liver disease; and in young people periorbital oedema in the mornings can be more prominent than ankle swelling.

Black

Don't forget that local factors can also cause oedema - venous or lymphatic obstruction, and inflammation, by increasing capillary permeability.

How is the glomerulus injured? ... diag of glom antigens

Most glomerulonephritis is autoimmune. The evidence for that comes from being able to see antibodies deposited, or cells of the immune system in glomeruli, or from the response to treatment with immunosuppressive drugs.

Of course there are other mechanisms. You can injure the glomerulus with toxins that directly target particular cell types. You can deposit abnormal material in the glomerulus so that glomerular functions are disrupted (the abnormal environment may prevent normal functioning of glomerular cells). Or you can have an inherited abnormality of a glomerular structure or cell.

The glomerulus has a restricted range

Now what about the consequences of these injuries.

Spectrum

The glomerulus is only able to show a limited range of responses to injury. It is helpful to think of glomerular diseases on a spectrum, with those at the left hand end causing pure proteinuria, to those at the right causing lots of haematuria with just a little proteinuria.

Nephrotic block to the left

You'll know from what went earlier that diseases causing proteinuria are going to be caused by injury to podocytes, or by scarring or deposition of abnormal material in the glomeruli so that it's not a friendly place for podocytes to live and function normally. The picture shows nodules of material deposited in diabetic nephropathy.

Nephritic block to the right

At the other end of the spectrum are the so-called nephritic diseases, characterised by inflammation, breaks in GBM, and reactive cell proliferation. At their most extreme there is crescent formation. The illustration shows proliferative, post-streptococcal disease.

Now we can place the major glomerular diseases along this spectrum. Each has its own appropriate piece of music, so as we get to the more aggressive end, the style of the music should change.

Now there are a couple of important diseases that can present in a number of ways that need to go along the top as they can't be placed at a single point on the spectrum.

3 nephrotic diseases

Now we're going to focus briefly on some of those individual diseases. First some from the left hand end of the spectrum. 3+2 diseases causing nephrotic syndrome.

Nephrotic syndrome

Most definitions of nephrotic syndrome are something like this, requiring heavy proteinuria, lowered serum albumin, and oedema.

Oedema is really a feature of nephrotic syndrome, not a complication, and it is caused not just by low serum albumin lowering oncotic pressure, but by avid renal sodium retention.

Complications

It is managed by sodium restriction and diuretics. It may be very diuretic resistant in severe cases and require combinations of diuretics, and sometimes intravenous treatment. However if fluid loss is too rapid there is a risk of electrolyte disturbances and even pre-renal failure.

Infection risk line

Infection risk is probably largely due to loss of immunoglobulins. The major risk is from the polysaccharide-encapsulated bacteria, pneumococci and meningococci, against both of which immunization can now give a good degree of protection.

Thrombosis line

Venous thrombosis - DVT or pulmonary embolus - is sometimes the presenting feature of nephrotic syndrome but can occur at any time and may involve the renal veins. If there is a spontaneous thrombotic event then presumably anticoagulation should last as long as the nephrotic syndrome, but prophylactic heparin should be used if there is any increased risk, for example immobility or long-distance air travel.

Hyperlipidaemia line

Cholesterol rises to extremely high levels in many patients. Most clinicians prescribe statins if there is is continuing proteinuria. Although there is no controlled trial evidence in this patient group, it is known that there is a greatly increased risk of cardiovascular disease.

Here then are the 3+2 diseases, and here is their position on the spectrum. [shud b longer]

Biopsy 1 – Minimal change

Now here is the first condition.

The appeareances are ... completely normal by light microscopy, earning this condition the name minimal change disease. However electron microscopy shows loss of foot process structure.

[needs FP fusion pics ... meantime descr over beginning next slide]

Minimal change nephropathy

Minimal change disease is the most common cause of nephrotic syndrome in Western Europe, though there are racial variations as well as geographical. It responds to corticosteroids and does not cause renal failure, but management can be difficult because of its tendency to relapse in many cases, mostly in children and young adults.

Response to treatment

This graph illustrates the response to steroid therapy, which is rapid in children. Where this disease is the commonest cause of childhood nephrotic syndrome, as in the UK, this response can be used as a diagnostic test, sparing most children a renal biopsy.

Adult line

In adults the response is slower and less complete, and there is a stronger probability of alternative diagnoses, so a renal biopsy is required unless it's obvious what the cause of nephrotic syndrome is, for example in a patient with longstanding diabetes and other microvascular complications, and a documented progression over years.

Biopsy 2 - FSGS

Here is the second biopsy.

It shows ... a rather solid looking pink segment at 6 o'clock, with normal looking segments on either side of it - a segmental scar. This is focal segmental glomerulosclerosis: focal meaning affecting only some glomeruli, segmental referring to the pattern within a single glomerulus. FSGS, little segmental scars.

In this context we are talking about a patient with new nephrotic syndrome, that is primary FSGS with nephrotic syndrome. However the appearance of lots of little scars can occur in other conditions, and some of these are listed here.

FSGS - causes of appearance

Primary FSGS

Concentrating on the primary condition, here are its key features.

It may be steroid responsive in a similar manner to minimal change disease, though steroid treatment may need to be prolonged to achieve remission. If there is a response to steroids, that is a good prognostic sign, as many with this diagnosis experience a progressive extension of the scarring to affect more and more glomeruli, over weeks or months or longer, often leading to end stage renal failure. Podocyte damage appears to be caused by a circulating factor which in some cases leads to development of proteinuria and recurrence of the disease within hours of transplanting a healthy kidney. The factor has so far eluded attempts at identification.

Biopsy 3 - Membranous

Now the third biopsy.

Here you can see ... a fairly uniformly thickened GBM - you couildn't cut yoruself on these capillary loops - and there is some increase in mesangium.

Immunofluorescence ... antigens diagram

Immunofluorescence shows a granular pattern of IgG decorating the outside of all the capillary loops. This is located under podocytes - subepithelial - and seems to be due to autoantibodies binding to a target on the surface of podocytes and becoming cross-linked there. The target in man is not yet know.

IF again - then text on Membranous

Membranous nephropathy is the third common renal disease that casues pure nephrotic syndrome in adults. A small proportion of cases can be attribute to drugs or toxins - usually penicillamine or gold prescribed for rheumatoid arthritis - and if so, stopping the responsible agent leads to slow recovery. Chronic hepatitis B and cancer may also cause it, but most are an idiopathic autoimmune condition in which a crude rule of thirds operates. A third get bettern, a hrid remain nephrotic, and a third deteriorate. Immunosuppressive therapy seems to increase the remission rate, but it is hazardous, so that it is reserved for patients who have demonstrated that they are deteriorating. Randomized controlled trials are under way.

Diabetic nephropathy

The remaining two conditions are architecture-altering diseases although it is possible that they also involve direct injury to podocytes.

Here is diabetic nephropathy, showing thickened GBM, increased mesangial matrix, and great nodules of deposited basement membrane-like matrix material. The thickened GBM could be a consequence of podocyte stress, but the podocytes certainly hate this very abnormal environment. They leak, heavy proteinuria is a prominent feature of diabetic nephropathy, and diabetic nephrotpathy is an important cause of endstage renal disease. ACE inhibitors have had a dramatic effect on the incidence and progression of this disease however, and this may be due to a direct effect on podocytes.

Amyloidosis

In amyloidosis the deposited material is amyloid fibrils, whichmay be made of immunoglobulin light chaines in B cell disorders, known as AL amyloid, or the acute phase protein serum amyloid A component, AA amyloid, and there are other rare variants too. Amyloid has this characteristic 'apple-green' birefringence when observed under polarise dlight.

Amyloid affects other organs too, but nephrotic syndrome is a common presentation. Renal failure will occur unless amyloid fibril formation can be stopped by reducing production of the precursor protein, for example by reversing the inmmune or infective cause of the inflammation giving rise to AA amyloid, or by anti-plasma cell treatment for AL amyloid. Involvement of other organs is particularly severe in AL amyloid, in which the heart, autonomic nerves, and gut are major targets.

Black - heading on Nephritic diseases

Now to the other end of the spectrum. , There are again 3+2 causes.

Nephritis and nephritic syndrome Causes - Manifestations

The description of nephritic synrome in all the textbooks is of an acute diseease with smokey or red urine, oliguria, hypertension and oedema. It comes from post-infectious or post-streptococcal glomerulonephritis, which may still be the most common of all these diseases worldwide, but which is now a rare disease in Western Europe, just like that other post-streptococcal syndrome, rheumatic fever.

Causes

It is still very common though in the third world, and some Eastern European countries that experienced economic collapse at the end of the 20th century saw big increases in incidence then.

The other rare disease on this list is anti-GBM disease, although this remains the archetypal aggressive and destructive disease, the immunology of which has taught us a lot about how glomeruli are damaged. The target antigen is also present in the alveolar basement membrane, so some patients present with teh combination of alveolar haemorrhage and rapidly progressive renal disease known as Goodpasture syndrome. [needs pics] However small vessel vasculitis is a more common cause of simultaneous aggressive nephritis and lung haemorrhage.

IgA immunofluorescence

... In Western Europe, typical acute nephritic syndrome is now more likely to be due to an exacerbation of IgA nephropathy, but this is just one of several presentations. This deposition of immunoglobulin A is the shared by all presentations, and the commonest appearance on a renal biopsy is an expansion of the mesangial matrix, and increase in the number of mesangial cells, as seen here. [get pic]

IgA nephropathy text - map

IgA nephropathy is the commonest type of glomerulonephritis in western Europe, and is also extremely common worldwide, although as this figure shows, its incidence varies enormously. The figures show the proportion of renal biopsies with IgA disease as the diagnosis, and this can be influenced by how aggressively you biopsy people with relatively mild renal disease. There seem to be strong genetic influences though, for example the condition seems to be rare not just in Africa, but also in African Americans in the USA, as shown by the 2% figure in brackets.

Presentations graph

An important feature of IgA nephropathy is that it is usually a very slowly evolving disease, grumbling over years and decades. It may present at any age, but the typical presentation varies at different ages.

Henoch Schonlein purpura is most often a childhood illness with rash, abdominal pain and haematuria.

The haematuria is caused by glomerulonephritis, and in children is usually mild. When this condition occurs in adults the glomerular disease is usually more severe. In both though, it is accompanied by IgA deposition in the mesangium. The disease is in fact a small vessel vasculitis and we will mention it again.

Students and others in their 20s who have this disease may notice red urine with a respiratory infection, and during these exacerbations they may also have hypertension and oedema, and renal impairment, just like post-streptococcal nephritis. Unlike childhood Henoch Schonlein purpura though, the urinary abnormalities and sometimes the hypertension and renal impairment do not completely resolve.

The next presentation is associated with pre-employment or pre-insurance medical examinations, when asymptomatic urinary abnormalities, with or without hypertension, are picked up. This group usually has no symptoms.

Alternatively the disease may be diagnosed a decade or several decades later by which time glomerular filtration rate has often been lost, and sometimes the patient may be near endstage renal failure, but still show haematuria and proteinuria.

Are these patients all the same? They certainly overlap, although most who present late give no history of red urine, or Henoch-Schonlein type rash, and neither are all those who present early necessarily fated to develop endstage renal failure. They are at increased risk of it though.

Vasculitis and FNGN

In this biopsy, there is a segmental lesion of the glomerulus at 12 o'clock. However there are no normal nuclei in it apart from the fragments associated with dying cells. This segment of glomerulus is necrotic - focal necrotising glomerulonephritis, caused by small vessel vasculitis within glomeruli. Even more obviously, the interstitium around the glomerulus is very inflamed too.

... crescent beginning

Severe nephritic disease like this can trigger an important chain of events that is just beginning in this picture. You can see a fibrin thrombus in two capillary loops, and in the lower one the fibrin is leaking into Bowman's space, where it has caused parietal epithelial cells to proliferate - the beginning of crescent formation. Crescents are a feature of the most aggressive nephritic diseases.

Severe crescentic nephritis

In this much more advanced example, all glomeruli have been affected by a catastrophic disease that has caused fragmentation of GBM in some glomeruli, and also rupture of Bowman's capsules, which seems to reduce the chances of healing.

Causes of crescents

Here is a short list of conditions that cause crescentic nephritis. Any nephritic, GBM-breaking type of nephritis can cause it if it is behaving at its most aggressive, but these are the most common causes.

They can cause renal function to deteriorate over days to weeks.

Top of the list of causes is vasculitis, inflammation of blood vessels.

Vasculitis classification diagram

Vasculitis is classified by the size of vessels it affects, so the types we're talking about that affect glomeruli are causes of small vessel vasculitis, towards the right of this diagram. Sometimes vasculitis occurs in other diseases, but most commonly glomeruli are affected by the primary types of small vessel vasculitis.

HSP pic again

Henoch Schonlein purpura, which we mentioned as a variant of IgA nephropathy earlier, is one of these.

This patient also had a vasculitic skin rash caused by exactly the same kind of process.

However the major group comprises the ANCA-associated types of vasculitis. The subtypes are not so important, as initial appearances and management are the same, but the most common are microscopic polyangiitis and Wegener's granulomatosis.

ANCA pic

ANCA are anti-neutrophil cytoplasm antibodies - as shown here, these bind to targets in the cytoplasm of normal neutrophils: in fact to the neutrophil granule enzymes myeloperoxidase and proteinase 3. They are very useful but not infallible guides to diagnosis in small vessel vasculitis.

Systemic vasculitis text

Systemic vasculitis can affect any organ with blood vessels in it - so that's any organ. It can occur in association with other diseases such as rheumatoid arthritis or systemic lupus erythematosus, but most that affect the kidney are primary. Most important of all, they are highly treatable.

Diagnosis of vasculitis text

They often present as a systemic illness that begins very non-specifically, may evolve to include arthralgia or arthritis, and weight loss is common.

I mentioned that ANCA can be very useful, but they aren't always positiv, and sometimes can be positive in other circumstances, particularly infection. Infection is an important differential diagnosis as conditions such as endocarditis may cause similar symptoms and signs and yet need very different treatments.

FNGN biopsy again

Biopsies of affected organs are very useful. In ANCA-associated vasculitis there is evidence of involvement of small blood vessels with little or no antibody deposition - so-called 'pauci-immune' glomerulonephritis. In Henoch Schonlein purpura you see IgA deposits in the mesangium.

Therapy graph

This is why it's important to make the diagnosis: here is a patient who presented with rapidly deteriorating renal function caused by crescentic nephritis, and high titres of anti-myeloperoxidase antibodies, in other words of antineutrophil cytoplasm antibodies, ANCA. Immunosuppression with cyclophosphamide and prednisolone, and plasma exchange, salvaged renal function and probably also prevented the patient from dying from vasculits affecting other organs.

Renal disease may be grumbling but is often progressing rapidly before the diagnosis can be made. Involvement of glomeruli is often associated with similar involvement of alveoli, leading to the combination of alveolar haemorrhage with rapidly progressive renal failure.

SLE histology ... immunofluorescence

The last condition is this one. You can see a glomerulus with far too many cells, proliferative glomerulonephritis, and with some capillary loops that are grossly thickened by immune deposits, as shown at two o'clock.

Immunofluorescence shows deposition of multiple immunoglobulins.

Lupus nephritis text

This is lupus nephritis. Systemic lupus erythematosus, SLE, most commonly affects young women, causing predominantly arthritis and systemic illness, and multiple other possible autoimmune manifestations. Antibodies to double-stranded DNA are characteristic. Significant renal disease is regarded as a marker of more severe lupus, though minor urinary abnormalities are probably common. Hypertension is usual but other manifestations, and histological appearances, are very useful. You just saw an example of diffuse proliferative glomerulonephritis, which responds to fairly heavy immunosuppression with cyclophosphamide along with prednisolone. Cyclophosphamide is usually given in monthly pulses, to keep side effects down, for up to a year. Alternative agents are being developed. Lupus is generally a chronic disease and there is a high risk of recurrent disease which means that most patients need to remain on immunosuppressive treatment for years.

Long term outcome of glomerulonephritis

Some types of glomerulonephritis may be long and grumbling, but even when it is a short, single-shot disease, it may leave scars that have lasting effects, predisposing to long term slow loss of glomerular filtration rate.

Markers of worse prognosis

Some of the markers associated with increased risk of this happening are listed here , , but even if there is no active inflammation to control, there are things that can be done about it, that you'll hear about elsewhere.