Minimal Change Disease Secondary to Hodgkin's Disease
Stephen M. Bonsib
Louisiana State University Health Science Center
The patient is a 19-year old white female. She was first seen by her family physician because of
acute onset of peripheral edema with swelling of feet and lower extremities. Two days before the patient
received vaccinations (hepatitis B and meningococcal) in preparation for college. She was treated with a
prednisone Dosepak pack with transient resolution of the edema. The edema recurred 1 week later and was
still present at a follow up visit 1 month later. 3+ proteinuria was detected and she was referred to a
The initial nephrology evaluation occurred 2 months after the first onset of edema. By that time she
had gained 8 kg. Physical examination was essentially unremarkable aside from significant edema. She
was afebrile, with blood pressure of 110/60 mm Hg, and weight of 72.4 kg.
No family history of renal disease.
Past medical history:
Recurrent upper respiratory infections characterized by tonsillitis
Creatitine: 0.5 mg/dl
No rbcs or cellular casts
24-hr urine protein: 6.5 gm
Serum albumin: 2.4 gm/dl
Cholesterol: 380 mg/dl / Triglycerides: 216 mg/dl
Slide 1 - H&E
Slide 2 - PAS
Figure 1 - The cortex appears normal; note absence of tubulo-interstitial disease.
Figure 2 - There are focal clusters of interstitial foam cells.
Figure 3 - There is no evidence of tubulo-interstitial changes. PAS stain.
Figure 4 - This glomerulus shows minimal mesangial matrix increase. PAS stain
Figure 5 - This is a normal glomerulus. PAS stain
Figure 6 - This is a normal glomerulus. Jones methenamine silver stain
Figure 7 - Direct immunofluorescence shows prominent mesangial deposition of IgA.
Figure 8 - This electron micrograph shows loss of podocyte foot processes. The mesangial matrix is not expanded and no electron dense deposits are present.
Figure 9 - This electron micrograph shows loss of podocyte foot processes. The mesangial matrix is not expanded and no electron dense deposits are present.
Nephrotic syndrome was diagnosed. She patient was treated with prednisone 60mg/day and given bactrim
for Pneumocystis prophylaxis. A renal biopsy was performed.
Nephrotic syndrome with normal renal function and no hematuria
Primary or idiopathic forms of glomerulonephritis
- Minimal change disease
- Focal segmental glomerulosclerosis
- Membranous glomerulonephritis
- Less likely, other primary gns
Secondary forms of glomerulonephritis
- Glomerulonephritis secondary to vaccination
- Mutation of podocyte foot process or slit diaphragm protein
- A post pharyngitic gn, such as an IgA neophropathy (but no hematruia)
- Connective tissue disease associated gn (but no clinical or serologic evidence of CTD)
Renal Biopsy Findings:
LM: The sections and special stains contain
35 glomeruli per section. No completely sclerotic glomeruli are present. There is no glomerular
hypercellularity or segmental lesion, and all glomeruli have open capillary loops with normal basement
membranes. There is no tubular atrophy or interstitial fibrosis, and no interstitial inflammation or
edema is noted. There are focal clusters of interstitial foam cells. All arterioles and arteries are
IF: The tissue contains 10 glomeruli. There
is a 1+ segmental mesangial reaction for IgA, C3, kappa, and lambda. There is no reaction for IgG, IgM,
C1q, or fibrin.
EM: Ultrastructural examination of 2 glomeruli
shows diffuse effacement of podocyte foot processes. The capillary loop basement membranes are uniform
and of normal thickness. There is no capillary loop sclerosis, hypercellularity, or electron dense
deposit. The mesangial matrix is not expanded and no electron dense deposits are noted.
Morphologic Diagnosis (Not Final Diagnosis):
Minimal change disease with 'incidental' IgA deposits
May, 2006 - Prednisone Dosepak
June, 2006 - Steroid taper
July 14, 2006 - Nephrology consult
- Resolution of edema
- Edema recurred 1 week later
July 27, 2006
- Nephrotic syndrome
- Wt 72.4 kg /6.5 gm
- Prednisone – 60 gm/day
- Renal biopsy performed
August 22, 2006
- Cervical lymphadenopathy noted
- CT scan – mediastinal lymphadenopathy identified - regarded as reactive
- Edema resolved / wt 68.3 kg
- Still on prednisone 60 gm/day - steroid taper initiated
August 29, 2006
- Repeat CT - suspicious for Hodgkin's disease
- Lymph node biopsy performed
- Prednisone taper at 30 gm/day
- Weight increased to 70.1kg
October 13, 2006
- Hodgkin's disease, nodular sclerosing type diagnosed
- Chemotherapy initiated - doxorubicin, bleomycin, vinblastine, DTIC / q2 weeks
- Prednisone 20 gm/day
- No edema / proteinuria resolved
- Chol 184 mg / TG 268 mg
- Creatinine 0.7mg/dl
- In remission
- Salb = 4.6 gm/dl / total protein = 7.1 gm/dl
- No proteinuria
Minimal change disease secondary to Hodgkin's disease
Possibly clincially precipitated by vaccination
"Incidental" IgA deposition
Possibly post pharyngitic-associated
Table 1 - Glomerulonephritis Associated with IgA Deposition
|Minimal change disease and incidental IgA|
IgA-dominant postinfectious glomerulonephritis
Mixed glomerulonephritis: IgA nephropathy and another glomerular disease
Liver disease and IgA nephropathy
Table 2 - Secondary Causes of Minimal Change Disease
|Drugs, especially NSAID|
Neoplasms, especially lymphoproliferative disorders
Intrinsic mutations of podocyte and slit diaphragm proteins: nephrin, podocin, -actinnin 4
Superimposed on another renal disease: IgA-N, SLE, HIV
Autoimmune and hypersensitivity disorders
Table 3 - Vaccinations and Nephrotic Syndrome
|1st Author - yr ||Vaccine ||Ren biopsy ||Onset - Labs ||Treatment ||Outcome|
|Kikuchi 2002 ||Pneumococcal ||MCD/AIN ||<1mo Crt 1.3/10.4gm ||corticosteroids ||Resol 32 days|
|Keilstein 2000 ||Influenza ||MCD ||4d -13.2 gm/65cc ||none ||Resol 6 wks|
|Islek 2000 ||Hep B ||MCD ||8d - 2 gm ||prednisone ||Resol 18 days|
|Ozdemir 1998 ||Hep B ||MCD ||17d - NRP ||corticosteroids ||Resol 20 days|
|Macario 1995 ||Hep B ||MCD ||'after' 2nd dose - 8 gm ||corticosteroids ||Resol 14 days|
|Carmeli 1993 ||Hep B ||No bx ||6 wks - 2+P / 1+ H ||none ||Resol 'few days'|
Nephrotic Syndrome: Hodgkin's Disease and Non Hodgkin's Lymphomas
0.4% incidence MCD, 0.1% incidence amyloid in series of 1700 patients
(see refs Plager, et.al. and Kramer, et al.)
Table 5 - Glomerular Diseases in Hematopoietic Malignancies
* Presenting symptom or occurs early, resolves with effective treatment of HD
(Data from Dabbs, et. Al. Am J Med 80:63-70, 1986)
|Glomerular lesion ||Hodgkin's disease ||NH Lymphoma ||CLL|
|Minimal change disease ||40 * ||5 ||2|
|Amyloidosis ||39 ** || ||3|
|Focal segmental glom scl ||2 ||1 |
|Membranous gn ||4 ||8 ||4|
|Membranoproliferative gn ||2 ||8 ||7|
|Other proliferative gn ||5 || ||3|
|Crescentic/AGBM ||6 *** ||3 |
|Unclassified gn ||2 ||7 |
**AA amyloid most cases recognized prior to 1960s, very rare since
*** All 6 AGBM disease
Table 6 - Minimal Change Disease in Patients with Hodgkin's Disease
** 3/5 cases that relapsed MCD, also relapsed HD in 7, 9, and 102 months
|1st Author ||Year ||# Pts ||Type HD ||Pre HD ||Post HD ||Co-exist ||NS Remit with HD|
|Audard ||2006 ||21 ||NS 71% ||8 * ||9 ||4 ||100% **|
|Eagen ||1977 ||26 || ||3 ||11 ||12 ||100%|
|Stephan ||1997 ||5/483 ||2NS/3MC ||2 || ||3 ||4/4|
* Only 60% of patients whose MCD preceded Hodgkin's disease remitted with steroids, most
Minimal Change Disease with IgA Deposits:
Vaccination-associated Nephrotic Syndrome:
- Association of IgA nephropathy
with steroid-responsive nephrotic syndrome. A report of the Southwest Pediatric Nephrology Study
Group. Am J Kidney Dis 5:157-164, 1985.
- Lai KN, Lai FM, Chan KW, et al. An overlapping syndrome of IgA nephropathy and lipoid nephrosis. Am
J Clin Pathol 86:716-723, 1986.
- Cheng IK, Chan KW, Chan MK. Mesangial IgA nephropathy with steroid-responsive nephrotic syndrome:
disappearance of mesangial IgA deposits following steroid-induced remission.
Am J Kidney Dis 14:361-364, 1989.
- Waldherr R, Rambausek M, Duncker WD, et al. Frequency of mesangial IgA deposits in a non-selected
autopsy series. Nephrol Dial Transplant 4:943-946, 1989.
- Bhandari S. The patient with acute renal failure and non-dilated urinary tract. Nephrol Dial
Transplant 13:1888, 1998.
- Őzdemir S, Bakkaloğlu A, Oran O: Nephrotic syndrome associated with recombinant hepatitis B
vaccination: a causal relationship or just a mere association? Nephrol Dial Transplant 13:1888-1889,
- Islek I, Cengiz K, Cakir M, et al. Nephrotic syndrome following hepatitis B vaccination. Pediatr
Nephrol 14:89-90, 2000.
- Carmeli Y, Oren R. Hepatitis B vaccine side-effect. Lancet 341:250-251, 1993.
- Macário F, Freitas L, Correia J, et al. Nephrotic syndrome after recombinant hepatitis B vaccine.
Clin Nephrol43:349, 1995.
- Kikuchi Y, Imakiire T, Hyodo T, et al. Minimal change nephrotic syndrome, lymphadenopathy and
hyperimmunoglobulinemia after immunization with a pneumococcal vaccine. Clin Nephrol 58:68-72, 2002.
- Kielstein JT, Termühlen L, Sohn J, et al. Minimal change nephrotic syndrome in a 65-year-old patient
following influenza vaccination. Clin Nephrol 54:246-248, 2000.
Nephrotic syndrome Assciated with Hodgkin's Disease
- Striker LM, Striker GE. Glomerular lesions in malignancies. Contrib Nephrol 48:111-124, 1985.
- Alpers CE, Cotran RS. Neoplasia and glomerular injury. Kidney Int 30:465-473, 1986.
- Ronco PM. Paraneoplastic glomerulopathies: new insights into an old entity. Kidney Int 56:355-377,
- Plager J, Stutzman L. Acute nephrotic syndrome as a manifestation of Hodgkin's disease. Am J Med
- Kramer P, Sizoo W, Twiss EE. Nephrotic syndrome in Hodgkin's disease. Report of five cases and
review of the literature. Neth J Med 24:114-119, 1981.
- Powderly WG, Cantwell BM, Fennelly JJ, et al. Renal glomerulopathies associated with Hodgkin's
disease. Cancer 56:874-875, 1985.
- Dabbs DJ, Striker LM, Mignon F, et al. Glomerular lesions in lymphomas and leukemias. Am J Med
- Peces R, Sánchez L, Gorostidi M, et al. Minimal change nephrotic syndrome associated with Hodgkin's
lymphoma. Nephrol Dial Transplant 6:155-158, 1991.
- Audard V, Larousserie F, Grimbert P, et al. Minimal change nephrotic syndrome and classical Hodgkin's
lymphoma: report of 21 cases and review of the literature. Kidney Int 69:2251-2260, 2006.