Introduction
Chronic Glomerulonephritis is a group of disorders in which glomeruli are predominantly involved due to an inflammatory process that does not abate; becoming indolent and frequently leading to glomerular destruction and End-Stage Renal Disease (ESRD).
In the majority of cases, the cause or initiating injury is not known whilst in some an infectious agent may be found, such as Streptococcal or Staphylococcal infection (throat, VP shunt, sub-acute bacterial endocarditis, abscesses, etc.), a viral infection like Hepatitis B, Hepatitis C, rarely CMV, HIV, EB viruses, parasitic infections like malaria and immunological diseases like SLE, HSP, Wegner's granulomatosis, Polyarteritis nodosa (in whom clinical clues such as joint pains, skin rash nodules, sinusitis, bronchitis are important for the correct diagnosis). Hence, before labeling a patient as primary or idiopathic CGN, serologic and immunologic tests eg. ASO Titre, ANA, AntidssDNA, ANCA, serum C3, and C4 levels, Anti-phospholipid antibodies (APLA), anticardiolipin, anti-SM, anti-GBM, and immune complexes should be examined.
The hallmark of chronic glomerulonephritis is proteinuria with or without hematuria, which is persistent and may be accompanied by edema, hypertension, azotemia, or renal failure.
Screening of school children for the presence of proteinuria +/- hematuria is one of the methods of diagnosis of glomerulonephritis in the asymptomatic stage. In developed countries like Japan, Taiwan, Korea, yearly urinalysis is mandatory and if 3-4 urinalysis are abnormal further investigations are asked to establish the diagnosis of chronic GN. This is not cost-effective in our country.
Typical age group: It is commonly found in school-going children especially above 6 years of age.
Suspect Chronic GN
- Acute glomerulonephritis is not completely resolved by 6-12 months i.e. urine shows proteinuria + hematuria, serum C3 is persistently low, hypertension, azotemia persist.
- Persistent urinary abnormalities - proteinuria, hematuria, isolated micro/macro hematuria
- Hypertension, nephritic syndrome
- Puffiness of eyes & edema, nephrotic syndrome
- Azotemia
- Systemic diseases like Henoch's Schonlein Purpura, SLE, Polyarteritis Nodosa, pulmonary-renal syndrome (Goodpasture's Syndrome).
- Nephritic syndrome
When to suspect?
In a patient with edema or hypertension, if urine tests show proteinuria/hematuria on at least 3–4 occasions, conducted one week apart, and there is no history of sore throat/pyoderma or typical features of post-streptococcal glomerulonephritis, then CGN may be suspected. In fact, in an asymptomatic child, urine examination may show the presence of proteins/RBCs which when repeated monthly may still be abnormal. That may be the first indication of CGN. These children usually become symptomatic within 6-12 months.
Frequently asked Questions
When do you do a renal biopsy in CGN?
As early as possible. Even when the child is asymptomatic, if urine shows persistent abnormalities, then a renal biopsy is indicated so that treatment can be started early to halt the progression of the disease. Once every 2-5 years, a biopsy may be required to check for the progression of the disease.
What is the treatment of CGN?
Treatment depends on the cause of the CGN. Most of the time steroids are the mainstay of therapy. In Wegner's and SLE, azathioprine & cyclophosphamide may be used in severe cases. All these are empirical treatments and not curative treatments.
When do these children develop ESRD?
If treated early and effectively, they usually end up in ESRD by the early twenties. However, untreated and undiagnosed patients usually succumb to the disease in the adolescent age almost within 5 years of onset.
Since renal transplant may eventually be required in these children, what are the chances that the disease may recur in the transplanted kidney?
The chances are as high as 50% in the case of membranoproliferative GN. But the good news is that, though the patient may have a recurrence in the form of proteinuria and histological abnormality, they do not go into renal failure again for almost their entire life.
What is the role of steroids in CGN due to hepatitis B virus?
Hepatitis B usually does not cause end-stage renal disease. In fact, these children usually die because of liver failure due to hepatitis B rather than renal failure. Interferon-alpha has been tried in these children and has been quite successful but its use in the case of CGN is controversial.
Regarding the use of steroids in a patient who is HBs Ag +ve, then the first rule out whether the child is a carrier. If the child is a carrier, the disease may not be due to Hepatitis B and the child may revert to HBs Ag negative status within 6 months. To prove that CGN is due to Hepatitis B, biopsy with viral culture may be required, which is not available here. However, if CGN is likely to be due to Hepatitis B, then steroids are contraindicated. In a carrier, you can wait till the serology becomes negative in 3-6 months, and then steroids can be started. Till then, only symptomatic and supportive treatment can be given in the form of antihypertensives and diuretics. Even if a child has Nephrotic syndrome with a positive Hepatitis B, then the treatment is the same.
What are chances of complete remission?
Complete remission is rare, however, there are documented cases of "burnt-out" disease, where the condition persists in a lingering, inactive state. In such cases, children have not progressed to renal failure. They require treatment for hypertension and edema but have not needed dialysis or a renal transplant.