Membranoproliferative glomerulonephritis in a patient with X-linked agammaglobulinemia

Immune complex and complement systems play an important role in membranoproliferative glomerulonephritis (MPGN). X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by severe hypogammaglobulinemia. We report the case of an XLA patient who developed MPGN during an intravenous immunoglobulin (IVIG) treatment. In this patient, the serum IgG level was maintained at more than 400 mg/dl of regular IVIG administration (2.5 g/dose/month). The patient presented with microscopic hematuria, proteinuria (U-pro/Cr: 4.0–4.2) and low serum complement levels (C3: 57.8 mg/dl) 3 years after IVIG treatment and was diagnosed histopathologically as having MPGN type III. Both hematuria and proteinuria significantly improved, and the serum complement level returned to a normal level following methylprednisolone pulse therapy. To our knowledge, this is the first case report of MPGN associated with XLA. Although it is unclear how MPGN occurred in this XLA patient, we suggest that residual humoral immunity in the patient could be associated with the development of MPGN.     

Membranoproliferative glomerulonephritis in a patient with Wilson's disease

Wilson's disease is an autosomal recessive disorder of hepatobiliary copper metabolism. Glomerular diseases can ensue during the course of Wilson's disease and membranous nephropathy is the eventual pathology in the majority of these cases. Membranoproliferative glomerulonephritis (MPGN) has rarely been reported in patients with Wilson's disease. Further, in this report, we present a patient with Wilson's disease who had developed MPGN during follow-up due to D-penicillamine therapy. This case is presented to draw attention to the rare association of Wilson's disease and MPGN and to discuss the possible underlying causes.     

Membranoproliferative glomerulonephritis associated with small cell lung carcinoma

An association between nephropathy and malignant solid tumours or with lymphoproliferative disorders was repeatedly reported. This association is mainly manifested by a nephrotic syndrome. In Lee's study [14], 11% of the adult nephrotics whom they had seen over a ten-year period developed a carcinoma. Membranous glomerulonephritis (MGN) is the most common glomerular disease associated with malignant solid tumour; the association of membranoproliferative glomerulonephritis (MPGN) with solid tumour is still uncommon. Although lung carcinoma is relatively common, the incidence of glomerular involvement with this tumour is quite rare. To date, only a few cases of lung cancer associated with nephrotic syndrome or glomerulonephritis have been reported by various authors. MGN is the most common glomerular lesion associated with these cases; however, MPGN has not been reported to be associated with lung cancer before. We report on a 45-year old man with nephrotic syndrome due to MPGN which in this case seemed to be a component of the paraneoplastic syndrome.     

Mesangiocapillary glomerulonephritis associated with meningococcal meningitis,C3 nephritis factor and persistently low complement C3 and C5

We report two unusual cases in which mesangiocapillary glomerulonephritis occurred in association with meningococcal infection. C3 nephritic factor, an autoantibody to alternate pathway C3 convertase, was present. Low serum complement C3 and C5 levels were also noted. The depressed complement levels, in conjuction with terminal complement complexes at the upper limit of normal, suggest activation of the early and late complement cascade. We suggest that children presenting with meningococcal infection should have a regular urine examination, as well as full complement measurements performed, in view of the association with hypocomplementaemic mesangiocapillary glomerulonephritis. Similarly, prophylactic penicillin should be prescribed for patients with mesangiocapillary glomerulonephritis and persistently low C5 levels to prevent meningococcal complications.     

Membranoproliferative glomerulonephritis and C3 glomerulopathy: resolving the confusion

Membranoproliferative glomerulonephritis (MPGN) denotes a general pattern of glomerular injury that is easily recognized by light microscopy. With additional studies, MPGN subgrouping is possible. For example, electron microscopy resolves differences in electron-dense deposition that are classically referred to as MPGN type I (MPGN I), MPGN II, and MPGN III, while immunofluorescence typically detects immunoglobulins in MPGN I and MPGN III but not in MPGN II. All three MPGN types stain positive for complement component 3 (C3). Subgrouping has led to unnecessary confusion, primarily because immunoglobulin-negative MPGN I and MPGN III are more common than once recognized. Together with MPGN II, which is now called dense deposit disease, immunoglobulin-negative, C3-positive glomerular diseases fall under the umbrella of C3 glomerulopathies (C3G). The evaluation of immunoglobulin-positive MPGN should focus on identifying the underlying trigger driving the chronic antigenemia or circulating immune complexes in order to begin disease-specific treatment. The evaluation of C3G, in contrast, should focus on the complement cascade, as dysregulation of the alternative pathway and terminal complement cascade underlies pathogenesis. Although there are no disease-specific treatments currently available for C3G, a better understanding of their pathogenesis would set the stage for the possible use of anti-complement drugs.     

Membranoproliferative glomerulonephritis associated with hereditary deficiency of the 4th component of complement

A 10-year-old female patient was found positive for urine protein and occult blood on Japanese school urinary screening. Examination of the blood was normal except low values of the complement system with CH50 13.5 U/ml, C3 45 mg/dl and C4 3 mg/dl. Renal biopsy demonstrated a focal membranoproliferative glomerulonephritis (MPGN). As for the activity of each component of the complement in the early stage of the disease, the C4 activity was markedly declined and the activity of classical pathway component was also decreased, but the activity of alternative pathway component was normal. On the HLA examination, the patient demonstrated a C4 double null haplotype (C4A2, Q0, BQ0 phenotype). A null C4 gene at both the C4A and C4B loci was found in her mother, aunt and grandfather on the mother's side and C4B null allele in her father and her grandmother on the mother's side. The development of the disease is found in 1 case and not in the other, although both have the genetic defect and the mechanism by which the complement is activated remains unknown. Thus, there appear to be many subjects to be studied as to the relationship between the defect of C4 gene and immune competence.     

Hypocomplementaemia of poststreptococcal acute glomerulonephritis is associated with C3 nephritic factor (C3NeF) IgG autoantibody activity

We have observed that decreased plasma levels of C3 in the serumof three children with poststreptococcal acute glomerulonephritis(PSAGN) at the time of presentation were associated with thepresence of C3NeF activity in purified serum IgG from the patients.C3NeF activity was determined using a sensitive assay measuringthe ability of patients’ IgG to stabilize a preformedcell-bound alternative pathway convertase complex. C3NeF activityof patients’ IgG decreased within weeks as plasma levelsof C3 progress ively returned to normal values. C3NeF activitybecame undetectable within 1–4 months following normalizationof plasma C3 levels. Our observations suggest that early alternativepathway-dependent hypo complementaemia, a cardinal feature ofPSAGN, is mediated by the transient expression of C3NeF autoantibody activity by patients’ IgG.     

Membranoproliferative glomerulonephritis associated with pulmonary sarcoidosis

A 34-year-old woman with pulmonary and ganglionary sarcoidosis developed a nephritic syndrome. The renal biopsy demonstrated a type-1 membranoproliferative glomerulonephritis. Clinical and histological remission of the renal disease following indomethacin treatment was associated with the remission of sarcoidosis. Prior reports have emphasized the association of a membranous glomerulonephritis with sarcoidosis. Temporal sequence of events and biological data suggest that hypocomplementemic membranoproliferative glomerulonephritis may be linked to sarcoidosis. The role of immune complexes in the pathogenesis of the 2 diseases is also discussed.     

Membranoproliferative glomerulonephritis associated with pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE) is a multiorgan disorder affecting mainly the skin, the eyes, and the cardiovascular system. A 51-year-old woman was admitted to our clinic complaining of weakness and swelling of her legs for the past two years. She had a proteinuria of 7.29 g/24 h. Renal biopsy was performed, and the histological diagnosis was membranoproliferative glomerulonephritis. Four weeks later, she was admitted to the hospital due to pain in her left hand and necrosis in the fourth and fifth fingertips of the left hand. A skin biopsy was performed from the forearm and was reported as PXE. Herein, we present a case of membranoproliferative glomerulonephritis accompanying PXE.     

Membranoproliferative glomerulonephritis and circulating cryoglobulins

Background

Previous studies on membranoproliferative glomerulonephritis (MPGN) and cryoglobulinemic glomerulopathy (CG) were based upon case series that were performed before hepatitis C virus (HCV) infection was routinely investigated. Therefore, it remains unknown how far HCV contributes to MPGN or CG, and there have only been a few reports about HCV-negative idiopathic MPGN.

Patients and methods

Thirty-five patients with MPGN diagnosed by renal biopsy who underwent examination for HCV infection at our institute between 1990 and 2008 were recruited for this study. Patients with HCV infection at presentation were included, but patients with complications such as underlying lymphoproliferative disorders, autoimmune diseases like lupus nephritis, infection, and liver disease due to hepatitis B virus or alcohol abuse were excluded. A total of 35 patients were enrolled and they were divided into two groups according to the presence/absence of circulating cryoglobulins (cryo). The 23 patients who had cryo-negative and HCV-negative idiopathic MPGN were divided into subgroups with type 1 and type 3 disease.

Results

In the cryo-positive group (n = 9), 7 patients were positive for HCV infection, while 2 patients were negative. In the cryo-negative group (n = 26), 3 patients were positive for HCV infection, while 23 patients were negative (idiopathic MPGN). Compared with the cryo-negative group, the cryo-positive group had several characteristics such as more severe thrombocytopenia, higher serum immunoglobulin (Ig)G and IgM levels, lower levels of hemolytic complement (CH50) and complement component (C)4, predominant IgM staining, and type 1 histology. Patients with cryo-negative and HCV-negative ‘idiopathic’ MPGN showed predominant staining for IgG in both type 1 and type 3 cases, unlike the predominant staining for IgM in the cryo-positive group. Compared with type 3 cases, type 1 cases had a younger age, lower levels of CH50, C3 and C4, and less proteinuria. In the cryo-positive group, 4 patients (44.4 %) died, with death from B cell lymphoma and liver failure in 2 patients each, while 1 patient (8 %) developed end-stage renal failure requiring dialysis. In contrast, all patients in the cryo-negative group remained alive during follow-up, although 4 patients (2 type 1 cases and 2 type 3 cases) required dialysis.

Conclusion

Cryo-positive MPGN shows a close relationship with HCV infection and IgM, resulting in a poor prognosis. Cryo-negative and HCV-negative idiopathic MPGN has a close relationship with IgG staining, and type 1 cases feature characteristics such as a younger age, more severe hypocomplementemia, and less proteinuria than in type 3 cases.