Year : 2009 | Volume
: 20 | Issue : 1 | Page : 116--119
Minimal change disease versus IgA nephropathy
Wael Latif Jabur
Nephrology Section, New Medical Center Specialty Hospital, Dubai, United Arab Emirates
Wael Latif Jabur
Specialist Nephrologist, NMC Specialty Hospital, P.O. Box 7832, Dubai
United Arab Emirates
IgA nephropathy is the most common type of the glomerulonephritis all over the world. However, its clinical presentation is variable, as is the underlying histopathological lesion. We report herein a case of an adult with steroid responsive minimal change disease and IgA mesangial deposits. During the first two weeks of therapy with prednisolone, the patient reported dramatic improvement in his clinical condition and remitted his disease. Unfortunately, at the end of the second month of prednisolone therapy, an acute flare of viral hepatitis was diagnosed. Interestingly, the acute viral flare was without a concomitant relapse of proteinuria.
|How to cite this article:|
Jabur WL. Minimal change disease versus IgA nephropathy.Saudi J Kidney Dis Transpl 2009;20:116-119
|How to cite this URL:|
Jabur WL. Minimal change disease versus IgA nephropathy. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2020 Sep 30 ];20:116-119
Available from: http://www.sjkdt.org/text.asp?2009/20/1/116/44717
IgA nephropathy is the most common type of the glomerulonephritis all over the world. However, its clinical presentation is variable, as is the underlying histopathological lesion. Abnormality of the IgA immunoglobuline molecule is widely blamed as the main culprit in its pathogenesis, and this hypothesis is the hub for a plenty of researches. Nephrotic syndrome is widely recognized in IgA nephropathy.
We report herein a case of steroid responsive minimal change disease and IgA mesangial deposits.
A 53-year-old man of African origin presented with a recent history of nephrotic syndrome, hypertension, and renal impairment. The past medical history was unremarkable for hematuria, proteinuria, hypertension, and diabetes. Drug history was negative.
On examination, the patient was hypervolemic and hypertensive with blood pressure of 180/100, otherwise unremarkable for other clinical findings.
Laboratory investigations revealed 24-hour proteinuria of 4 grams, no active urine sediment, serum creatinine of 1.7mg/dL, serum albumin of 2 gm/dL, normal complement system levels, negative antinuclear antibodies (ANA), negative anti-nuclear cytoplasmic antibodies (ANCA), and negative paraproteinemia assays. Virology screening he was positive for hepatitis B viral antigen (HBsAg) without evidence of active replication (viral copies were less than 100,000/ mL and HBeAg was negative) and the serum transaminases were normal. We did not check for viral genotype. The rest of investigations were unremarkable.
Kidney biopsy was performed after controlling blood pressure and volume status. Hematoxylin and Eosin light microscopy examination revealed normal capillary loops mild focal increase of the mesangial cells, and no extra capillary proliferation. Periodic Acid Schiff staining revealed mild diffuse mesangial matrix accentuation and the silver staining showed normal capillary walls, while the Congo red staining for amyloidosis was negative. Similarly, the Mason trichrome staining showed normal tubules and interstitium. Immunoflourescent study was strongly positive for IgA, IgG and C3 complement in the mesangium and the capillary walls. Electron microscopy spotted the presence of dense deposits in the mesangium [Figure 1] and the subendothelial area [Figure 2], with mild mesangial expansion and diffuse foot processes effacement and focally thinning of otherwise intact basement membrane. There was no evidence of intracellular inclusion bodies.
A diagnosis of IgA nephropathy associated minimal change disease was suggested and a therapeutic regimen consisted of prednisolon of 1 mg/kg body weight, a loop diuretic, calcium 500 twice daily, resuvastatin 5 mg/day, and multivitamins was initiated. The patient was followed weekly as an outpatient to check for urine protein, blood pressure, and for probable complications of the therapy.
During the first two weeks of therapy, the patient reported dramatic improvement in his clinical condition, and at the end of the third week the urine was protein free, serum albumin was 3.7 mg/dL, and serum creatinine was 1.0 mg/dL. The prednisolone dose was maintained till the end of the second month and then tapered to 40 mg every other day. Unfortunately, at the end of the second month an acute flare of viral hepatitis was diagnosed, with a viral load of 400,000 copies/mL, and three folds elevation of the transaminases. Accordingly, an antiviral protocol consisted of Adivofir 10 mg/day was started. Interestingly, the acute viral flare was without a concomitant relapse of protienuria.
The clinical presentation and the rapid remission of the nephrotic syndrome on prednisolone are consistent with minimal change disease (MCD). Despite the fact that the association of minimal change disease and IgA nephropathy is well known, it is very rarely if ever reported to my knowledge the solely presentation of MCD with IgA nephropathy as the nephrotic syndrome without hematuria. ,,
Mesangial IgA deposits are the defining hallmark of IgA nephropathy accompanied by complement C3 and some times IgG deposition, with variable histopathological patterns. According to Lee and Haas classification,  our patient has stage 1 IgA nephropathy. The common presentation of such a patient should be macroscopic and microscopic hematuria with variable degree of proteinuria. However, it is not uncommon to find a patient with significant histological damage despite the absence of clinical risk factors. 
It is very rare for proteinuria to occur without microscopic hematuria in IgA nephropathy, and the nephrotic syndrome was reported to occur in 5% of the patients during the course of IgA nephropathy. 
IgA nephropathy might be associated with the nephrotic syndrome at any stage of the disease and it is probably attributable to a concomitant minimal change nephropathy in the early stages and to mesangial sclerosis and crescentic glomerulonephritis in the advanced stages. 
Despite the fact that the IgA immunoglobulin deposits in the capillary walls in addition to the mesangial deposits are usually associated with a poor prognosis, , our patient's nephrotic syndrome was sensitive to steroid and his short term prognosis was very good, in contrast to some previous reports that showed more slower response to the steroid therapy. 
The hallmark of the MCD is the normal histology on light microscopy, absence of the immunoglobulins on immunoflourescent study, and characteristically diffuse foot processes effacement on electron microscopic examination. Several variants of MCD are well recognized that include mesangial hypercellular, IgM nephropathy, and C1q nephropathy. , Many authors recognize the variants of MCD as different diseases and have considered their clinical behavior more consistent with idiopathic focal segmental glomerulosclerosis (FSGS) than MCD, which is not the case in our patient. 
Mesangial expansion and hypercellularity are a nonspecific response to injury, which might be mediated by up-regulation and secretion of tissue growth factor (TGFI3), such as the deposition of immune-complexes, immunoglobulins, and complement,  or it might be idiopathic as in mesangial proliferative variant of MCD. In our case, we could not consider the mesangial proliferation as an idiopathic variant due to the presence of a significant mesangial IgA deposits. The presence of IgA mesangial and capillary deposits in the context of the nephrotic syndrome and negative urine sediment might represent more an early asymptomatic (Lanthanic) IgA nephropathy  with a concomitant minimal change disease. On the other hand, the lack of the urinary active sediment and the dramatic response to the steroid may be explained by a new variant of MCD. The response to therapy with steroids is more consistent with MCD than FSGS.
The etiology of acute renal failure that observed in adult MCD is usually due to acute tubular necrosis in severe cases, otherwise mild renal failure reported in hypervolemic patients is usually due to renal interstitial edema, which most probably was the case in the index patient because of the rapid and marked improvement with therapy.
The patient flare of the viral hepatitis highlights the debate of administering prophylactic antiviral therapy for the patients who are carriers of the hepatitis virus, , while they are maintained on long-term steroid therapy. This is in agreement with Oren Shibolet et al study, which recommended the use of prophylactic antiviral therapy for any patient who is a HBV carrier (with or without active viral replication) while undergoing immunosuppressive protocol.  Because of the current remission of the nephrotic syndrome in the face of relapse of active viral hepatitis, we may conclude that the viral hepatitis infection was not temporally related to the pathogenesis of IgA or minimal change disease.
|1||Cyclosporin A therapy in frequently relapsing nephrotic syndrome and IgA nephropathy. Nephrol Dial Transplant 1997;12(11):2402-4.|
|2||Nator SN, Strom JA, Occi A. Relapsing nephrotic syndrom in a patient with Kimura s disease and IgA nephropathy. Nephrol Dial Transplant 1998;13(9):2358-63.|
|3||Boix E, Rivera F, Gil CM, Perez-Contreras J, Olivares J. Nephrotic syndrome with minimal change disease and IgA deposits in a HIVinfected patient. Nephrol Dial Transplant 2000; 15(3):412-4.|
|4||Li PK, Ho KK, Szeto CC, Yu L, Lai FM. Prognostic indications of IgA nephropathy in the Chinese-clinical and pathological perspective. Nephrol Dial Transplant 2002;17(1):64-9.|
|5||Barratt J, Feehally J. IgA nephropathy. J Am Soc Nephrol 2005;16(7):2088-97.|
|6||Tumlin JA, Lohavichan V, Hennigar R. Crescentic, proliferative IgA nephropathy: Clinica and histological response to methylprednisolon and intra-venouse cyclophosphamide. Nephrol Dial Transplant 2003;18(7):1321-9.|
|7||Tumlin JA, Mdaio MP, Hennigar R. Idiopathic IgA Nephropathy: Pathogenesis and therapeutic options. J Am Soc Nephrol 2007;18(5):1054-61.|
|8||Waldman M, Crew RJ, Valeri A, et al. Adult minimal change disease: Clinical characteristics, treatment and outcome. Clin J Am Soc Nephrol 2007;2(3):445-53.|
|9||Howie AJ. Pathology of minimal change disease and segmental sclerosing glomerular disorders. Nephrol Dial Transplant 2003;18 (Suppl 6):VI33-8.|
|10||Alexopoulos E, Papagranni A, Stangon M, Pantzaki A, Papadimitriou M. Adult onset idiopathic nephrotic syndrom associated with diffuse mesangeal hypercellularity. Nephrol Dial Transplant 2000;15(7):981-7.|
|11||Suzuki K, Honda K, Tanabe K, Toma H, Nihei H, Yamaguchi Y. Incidence of latent mesangial IgA deposition in renal allograft donors in Japan. Kidney Int 2003;63(6):2286-94.|
|12||Tsou PL, Lee HS, Jeng YM, Huang TS. Submassive liver necrosis in a hepatitis B carrier with cushing syndrom. J Formos Med Assoc 2002;101(2):156-8.|
|13||Shibolet O, Ilan Y, Gillis S, Hubert A, Shouval D, Safadi R. Lamivudin therapy for prevention of immunosuppressive-induced hepatitis B virus reactivation in HBs Antigen carriers. Blood 2002;100(2):391-6.|