JOURNAL OF INSURANCE MEDICINE
Copyright 䊚 2000 Journal of Insurance Medicine
J Insur Med 2000;32:186–188
CASE STUDY
Membranoproliferative Glomerulonephritis
Robert E. Frank, MD
Glomerulonephritis (GN) encompasses a wide variety of primary
and secondary diseases that cause injury to the functioning unit of
the kidney, the glomerulus. The many classifications of GN sometimes lead to confusion. This case study describes an individual
with membranoproliferative GN and includes discussion of classification, treatment, and prognosis of this disease.
Address: 8613 Kirkhill Court, Dublin, OH 43017
Correspondent: Robert E. Frank,
MD, e-mail: resafrank@aol.com.
Keywords: Glomerulonephritis,
membranoproliferative glomerulonephritis, nephrotic syndrome.
Received: May 10, 2000.
Accepted: May 31, 2000.
and his creatinine clearance was 86 ml/min.
The only other information was that 1 year
after cessation of treatment his blood pressure was normal, and a urinalysis was negative for proteinuria.
CASE REPORT
An application for a $250,000 term policy
was received from a 36-year-old male. On the
application, he admitted to a history of a renal problem, but all tests were normal on his
latest laboratory studies. His blood urea nitrogen and creatinine levels were 18 mg/dL
and 1.3 mg/dL, respectively. The urinalysis
was negative for proteinuria and red blood
cells. The lipids were normal. His blood pressure was normal at 136/84.
An attending physician’s report was obtained, and it was noted that he had a history
of glomerulonephritis (GN), having presented with the nephrotic syndrome 8 years before. A renal biopsy was done at age 28 and
showed membranoproliferative GN (MPGN).
He had nephrotic range proteinuria, but his
creatinine clearance was 112 ml/min. The records were not complete, but he had apparently been treated with some types of medication for approximately 2 years. At the end
of treatment, his proteinuria had resolved
DISCUSSION
Many physicians, insurance medical directors included, are thrown into obfuscation
when they hear the term glomerulonephritis.
GN refers to a wide variety of diseases that
cause inflammation and injury to the glomerulus. Glomeruli are complex, with 3 types of
cells—the mesangial cell, the glomerular endothelial cell, and the visceral epithelial cell
also called the podocyte. You can have injury
to 1 or more of these cells, with humoral and
cell-mediated immunological processes being
responsible for the injury. There are many
different ways to classify GN, and this also
leads to confusion. Classifications have categorized GN by the mechanisms underlying
the injury, the renal injury itself, the site of
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immune deposition, what antibodies may be
involved, whether the morphology shows
proliferative or nonproliferative changes, and
even the levels of serum complement.1, 2
In addition, the injury may be primary to
the kidney or a secondary injury from a wide
variety of systemic diseases. They can be classified as antineutrophil cytoplasmic antibody
positive or negative. They also can have a
wide variety of clinical presentations, including acute and chronic onsets. The nephritic
syndrome is characterized by hypertension,
edema, an active urinary sediment (red blood
cells and red blood cell casts), proteinuria of
⬍3.5 g/d, and often a reduced glomerular filtration rate. The nephrotic syndrome presents
with edema, low albumin, elevated lipids,
and proteinuria of ⬎3.5 g/d.
Patients can present with asymptomatic hematuria (eg, IgA nephropathy); acute GN
with gross hematuria, oliguria, and renal failure (eg, poststreptococcal GN); the nephrotic
syndrome (eg, cancers such as Hodgkin’s disease); rapidly progressive GN with hematuria, proteinuria, and loss of renal function
within a short period of time (eg, Goodpasture’s syndrome); and chronic GN with an active urine sediment, hypertension, and often
progressive loss of renal function (eg, Lupus
nephritis). Renal biopsy is necessary to establish the precise diagnosis, and is useful in
guiding therapy. But often, the biopsy is not
performed or is postponed.
In the United States, GN ranks behind hypertension and diabetes mellitus as the more
common causes of end-stage renal failure, but
worldwide, GN is the most common single
cause of end-stage renal failure. Treatment is
directed towards treating the specific primary or secondary renal pathology, treating
the complications such as hypertension, trying to decrease further renal damage with
nonspecific measures, and prevention of future complications. The risk of end-stage renal disease varies according to the actual underlying pathology, plus the success of these
interventions. A wide variety of immunosuppressive drugs may be used.
MPGN, the type present in our proposed
insured, is also referred to as mesangiocapillary GN. It is not uncommon, accounting for
perhaps 10%–20% of all primary GN. It is
usually a primary process, although secondary causes do occur. The secondary causes encompass numerous etiologies, including collagen vascular disease, complement deficiency, cryoglobulinemia, bacterial and viral infections (such as hepatitis B, hepatitis C,
HIV), malignancies, and many others. The
secondary causes need to be properly evaluated and ruled out. It can present as the nephritic or nephrotic (most common) syndrome, as well as acute renal failure. The association of MPGN with such a wide variety
of diseases has led some to postulate that it
is not a single entity.3
MPGN is divided into 3 types, based on
the site of immune deposition. Type 1 shows
immune deposition in subendothelial and
mesangial areas with activation of the classical complement pathway. Chronic hepatitis C
is one cause of this type of disease. Type 2,
also referred to as dense-deposit disease,
shows immune deposition in the basement
membrane itself, with activation of the alternative complement pathway. Type 3 is similar to Type 1, but there are also deposits beneath the podocytes.
Treatment is somewhat controversial. Secondary causes must be evaluated, and if present, the underlying primary disease can be
treated. Steroids are usually given to children. Adults may be treated with steroids,
immunosuppressive drugs, or both. Generally speaking, prognosis depends on the creatinine clearance value, urine protein excretion of ⬎3 g/d, presence of hypertension, and
the extent of scarring on renal biopsy.4 The
greater number of these factors present, the
worse the prognosis. Spontaneous remissions
are rare in the primary type. Without immunosuppression therapy, the risk of endstage renal disease is significant. Forty to 50%
of people who do not respond to treatment
will progress to renal failure within 10 years.5
Those who do respond to treatment usually
have an excellent prognosis. It should be remembered that chronic proteinuria itself can
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cause further glomerular damage, and hypertension accelerates this process. However,
prognosis has varied considerably, with anywhere from 16%–82% of total presenters having renal failure by 10 years. Even at 10 years,
a patient with a normal serum creatinine may
still have further degeneration of renal function.
So how do we apply all of this information
to our proposed insured? He presented with
the nephrotic syndrome, one of the poorer
prognostic signs. His renal function was normal, although his creatinine clearance declined by 23% over 2 years. Six years later,
his creatinine was normal, but this does not
preclude some further deterioration of his
creatinine clearance. His proteinuria resolved
with therapy, and remains resolved on current testing. He currently is normotensive
without therapy. It can safely be considered
that he responds to therapy, although only 6
years have elapsed since treatment. I feel that
such an individual has a close to standard
mortality ratio. If he had not responded to
therapy, the proteinuria would have persisted
and probably would have been accompanied
by hypertension and gradual deterioration of
renal function. If this were the case, the prognosis would be similar to all persons with
end-stage renal failure, and mortality ratios
would be extremely high. Mortality of individuals on long-term dialysis may approach
20% per year, and 5-year survival rates for
renal transplantation are no better than 55–
60%.
REFERENCES
1. Rick DE, Chung-Park M, Sedor JR. Glomerulonephritis. N Engl J Med. 1998;339:888–899.
2. Madiao MP, Harrington JT. The diagnosis of acute
glomerulonephritis. N Engl J Med. 1983;309:1299–
1312.
3. Shankland JSJ. Glomerular diseases. In: Dale DC,
Federman DD, eds. Scientific American Medicine. Vol
10. New York, NY: Scientific American; 2000:1–15.
4. Nahman S. Insurable glomerulopathies. Paper presented at: Midwestern Medical Directors Association Meeting; November 1999; Nashville, TN.
5. Rennke HG. Secondary membranoproliferative
glomerulonephritis. Kidney Int. 1995;47:643–650.
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