IgA-associated glomerulonephritis with membranoproliferative glomerulonephritis-like pattern in two children

In this article, we report two patients with IgA-associated glomerulonephritis with a membranoproliferative glomerulonephritis (MPGN) -like pattern. Both patients had nephrotic syndrome at onset. One patient was treated with high-dose alternate-day prednisolone (PSL), and the other with indomethacin and low-dose PSL. One lost the urinary abnormalities 3 years after starting treatment. The other lost the nephrotic state and hematuria over a 5-year period, but proteinuria persisted until the last follow-up. Both patients had diffuse proliferative changes with mesangial interposition and subendothelial deposits, associated with strongly positive deposits of C3 and IgA along the capillary walls of the glomeruli. These two patients showed histological changes compatible with type-I MPGN, but the pattern of IgA deposits was not typical of idiopathic MPGN or IgA nephropathy. We assume this is a rare form of MPGN, not associated with liver disease or other systemic diseases.     

Decreasing incidence of membranoproliferative glomerulonephritis in Spanish children

Thirteen paediatric nephrology units contributed to a retrospective review of 1447 kidney biopsies which were performed on children under 15 years of age from 1972 to 1986 and were examined by immunofluorescence and light microscopy. The histological studies were grouped into three 5-year periods: (1) 1972–1976 (248 biopsies), (2) 1977–1981 (607 biopsies), and (3) 1982–1986 (592 biopsies). The incidence of membranoproliferative glomerulonephritis (MPGN) was significantly lower during periods 2 (6.6%) and 3 (5.4%) than in period 1 (10.9%,P<0.05 and <0.01 respectively). The reasons for the significant decrease in the incidence of MPGN in Spanish children cannot be determined, but the observation agrees with those from French, Italian and Spanish studies involving adult patients.San Juan de Dios (Barcelona); Vall d'Hebron (Barcelona); Enrique Sotomayor (Bilbao); La Paz (Madrid); Niño Jesus (Madrid); Gregorio Marañon (Madrid); Ramon y Cajal (Madrid); General de Asturias (Oviedo); Virgen de Covadonga (Oviedo); Valdecilla (Santander); Virgen del Rocio (Sevilla); La Fe (Valencia); Miguel Servet (Saragossa). Offprint requests to: N. Gallego, Servicio de Nefrologia, Hospital Ramon y Cajal, Carretera de Colmenar Km 9.100, E-28034 Madrid, Spain     

Malignancy-associated membranoproliferative glomerulonephritis

An 11-year-old girl with an abdominal desmoplastic round cell tumor, treated with chemotherapy, presented with gross hematuria and proteinuria. Renal biopsy revealed type I membranoproliferative glomerulonephritis (MPGN). The association of a malignant tumor and MPGN is extremely unusual in children, and the pathogenesis of the renal lesion under these circumstances is unknown. Received June 23, 1994; accepted in revised form July 10, 1996; accepted July 11, 1996     

A patient with membranoproliferative glomerulonephritis diagnosed by the third biopsy via endocapillary proliferative glomerulonephritis and focal membranoproliferative glomerulonephritis

We present a girl with type I membranoproliferative glomerulonephritis (MPGN) diagnosed by the third renal biopsy. The first renal biopsy was performed at age 11.2 years after microscopic hematuria (which was revealed by school urinary screening) had persisted for 3 months, along with a low level of serum C₃. Pathological examination of the biopsied specimen revealed endocapillary proliferative glomerulonephritis with multiple humps. The serum C₃ level increased to within the normal range 2 months after the first renal biopsy, and the microscopic hematuria disappeared at age 12.3. However, microscopic hematuria, proteinuria, and the low serum complement level reappeared at age 12.8. Pathological examination of a further renal biopsy that was performed at age 13.2 revealed focal MPGN with humps. Prednisolone therapy was subsequently initiated. Fluvastatin was added to her treatment regime when she developed hypercholesterolemia at age 13.6 and was continued even after normal cholesterol levels were reestablished. Pathological examination of the third renal biopsy, which was performed at age 15.2, revealed type I MPGN with humps. Serum C₃ normalized 6 months after the cessation of prednisolone at age 15.9. It is clinically important that patients with nontypical acute glomerulonephritis should be observed over a long period and repeated renal biopsies should be performed.     

Specific eye fundus lesions in type II membranoproliferative glomerulonephritis

In three adolescents, suffering from membrano-proliferative glomerulonephritis type II, ophthalmoscopy and fluorescein angiography revealed retinal pigment epithelium lesions, referred to as basal laminar drusen. The patient with the longest renal history had the most pronounced fundus changes. These lesions, earlier described in adult patients, are believed to be specific for this particular form of chronic glomerulonephritis.     

Focal segmental membranoproliferative glomerulonephritis in children

Eight patients with focal segmental membranoproliferative glomerulonephritis (FSMPGN) were followed for 5–16 years. Their urinary abnormalities were detected by school urinary screening in seven, and one patient presented with nephrotic syndrome. All but one patient were treated with alternate-day (ALD) prednisolone. With time, urinalysis became normal in six and two continued to have proteinuria with or without hematuria. Serum albumin, cholesterol, and creatinine levels were normal at the last follow-up. Serum C3 returned to normal levels in six, but remained persistently decreased in two. Mesangial proliferation and matrix changes in glomeruli without MPGN lesions were mild. Subendothelial and mesangial electron-dense deposits and deposits containing C3 along capillary walls and mesangium were observed. MPGN lesions and mesangial proliferation improved. No severe growth retardation was observed, but the duration and dosage of ALD prednisolone could be reduced further, since the patients with FSMPGN seemed to have an excellent prognosis.     

A case of autoimmune thyroiditis and membranoproliferative glomerulonephritis

Thyroid hormones play an important role in the growth of the kidney and maintenance of its functions. Prolonged hypothyroidism is known to be accompanied by changes in renal morphology such as thickening of the glomerular and tubular basement membranes as well as increased mesangial matrix. Increased transcapillary leakage of plasma proteins leading to proteinuria and generalized edema is also a known complication of hypothyroidism. In particular, autoimmune thyroiditis is associated with proteinuria. Most previous reports of autoimmune thyroiditis with nephrotic syndrome have demonstrated mixed pathological morphology marked by predominant membranous glomerulopathy. Here we present a patient whose initial presentation with profound hypothyroidism and autoimmune thyroiditis was dominated by nephrotic syndrome secondary to type 1 membranoproliferative glomerulonephritis (MPGN). The association of MPGN and autoimmune thyroiditis is very rare.     

Prognostic factors in children with membranoproliferative glomerulonephritis type I

The clinical outcome of patients with membranoproliferative glomerulonephritis (MPGN) varies, with some patients progressing to end-stage renal disease. The aim of this retrospective study was to analyze the initial clinical signs and laboratory test results associated with an MPGN prognosis. The study cohort consisted of 47 patients with idiopathic MPGN Type I treated at the National Institute of Pediatrics, Mexico City, between 1971 and 2001. The median follow-up was 3 years. The three different outcomes of interest were death, renal failure, and nephrotic syndrome. The patients’ ages ranged between 4 and 16 years. All patients had different degrees of proteinuria, hyperlipidemia, and microscopic/macroscopic hematuria, and 85.1% of them showed hypocomplementemia. Clinical outcomes varied, however, the most common was nephrotic syndrome, either alone or combined with other syndromes, which accounted for 74.5% of all cases. Fifteen patients died. Treatment with methylprednisolone improved the patient’s condition, while the use of chloroquine or cyclophosphamide worsened it. Twenty-two patients had some degree of renal failure; glomerular filtration rate (GFR) levels and albumin values were negatively associated to renal failure, while treatment with methylprednisolone decreased the probability of renal failure. Nephrotic syndrome persisted in 18 patients; hemolytic complement and hemoglobin values were negatively associated with nephrotic syndrome, while macroscopic hematuria was positively associated with it. Signs that suggested a poor prognosis during diagnosis were low GFR, low albumin, low hemolytic complement, and macroscopic hematuria. Treatment with methylprednisolone seemed to improve prognosis, however, this needs to be confirmed with randomized studies.     

Decreasing hypocomplementemia and membranoproliferative glomerulonephritis in Japan

The number of patients with membranoproliferative glomerulonephritis(MPGN) diagnosed in our institution and the incidence of hypocomplementemia as determined by school urinary screening programs in Japan were investigated retrospectively. Fifty-seven children were diagnosed as having MPGN between 1974 and 1997. Of these, 13 patients were diagnosed during period 1 (1974–1979) and 25 during period 2 (1980– 1985). A decreasing trend was observed during periods 3 (1986–1991) (12 patients) and 4 (1992–1997) (7 patients) compared with period 2 (P<0.05 and P<0.01, respectively). A significant difference was also noted when MPGN was compared between periods 1 and 2 (1974– 1985) and periods 3 and 4 (1986–1997) (P<0.01). Serum C3 was measured in 1,282 school children with abnormal urinary findings between 1980 and 1997. Thirty children had hypocomplementemia. The incidence of hypocomplementemia was significantly lower in period 3 (1986–1991) (9 children) and period 4 (1992–1997) (2 children) compared with period 2 (1980–1985) (19 children) (P<0.05 and P<0.01, respectively). New cases of MPGN in our institution and the incidence of hypocomplementemia as determined by school urinary screening programs are decreasing in Japan. The reason for this trend is unknown. Received: 10 August 1999 / Revised: 22 November 1999 / Accepted: 23 November 1999     

Successful steroid treatment in a patient with membranoproliferative glomerulonephritis associated with hepatitis C virus

Thirteen years ago, a 65-year-old woman was diagnosed to have chronic active hepatitis with hepatitis C virus. After starting interferonα administration, she noticed edema and hypoalbuminemia. Renal biopsy revealed mesangial proliferation with focal endocapillary proliferation, and double contour of the glomerular basement membrane due to mesangial interposition. Interferonα was discontinued, and proteinuria and edema gradually decreased. She was re-admitted due to a relapse of proteinuria 8 years later. Biopsy revealed moderate mesangial and endcapillary proliferation presenting a lobular pattern, in addition to the presence of hyaline thrombi. Granular staining of immunoglobulin M and of C3 in capillary walls were detected. Since cryoglobulinemia was positive, a final diagnosis of cryoglobulinemic membranoproliferative glomerulonephritis was made. Prednisolone was started with an initial dose of 20 mg/day. Proteinuria and hypoalbuminemia improved, and prednisolone was tapered to 5 mg/day 9 months after the 2nd renal biopsy. The hepatitis C virus-RNA titer fluctuated.     

Idiopathic membranoproliferative glomerulonephritis in childhood

Membranoproliferative glomerulonephritis (MPGN), recognized since 1965, is now known to have three forms, designated types I, II, and III. The types are similar in the frequency of hypocomplementemia and clinical course but are dissimilar in glomerular ultrastructure, pathogenesis, mechanisms of complement activation, predisposition to recur in the renal transplant, and, to some extent, in clinical presentation. Although glomerular proliferation is usually diffuse, it may be focal and segmental particularly in mild cases of MPGN I. Hypocomplementemia, present in about 80% of patients, is the result of hypercatabolism of C3 by three mechanisms as well as of diminished C3 synthesis. The hypocomplementemia is unrelated to clinical course or prognosis. Although MPGN I and III both have a high frequency of an extended haplotype on chromosome 6, which has known associations with autoimmune phenomena, and both have a high frequency of inherited complement defects, they are nevertheless dissimilar in glomerular ultrastructure, complement profile, and immunohistology in ways which suggest a wide difference in pathogenesis. Abnormalities in humoral immunity appear not to be involved in MPGN III. Treatment with anticoagulant, antiplatelet and cytotoxic drugs have, in controlled trials, been either ineffective or marginally effective. Long-term use of alternate-day prednisone in high dosage appears to be the most efficacious regimen in both controlled and uncontrolled studies.     

The co-existence of membranoproliferat?ve glomerulonephritis type?1 and coeliac disease: a case report

Coeliac disease is an autoimmune enteropathy characterised by chronic inflammation of the small intestinal mucosa and the presence of typical autoantibodies. Coeliac disease may be a risk factor for renal disease. Immunoglobulin A (IgA) nephropathy is reported in the majority of these cases. Only one adult patient had been reported with membranoproliferative glomerulonephritis (MPGN) and coeliac disease. Here, we report a case in a 12-year-old girl with coeliac disease who presented with severe anaemia and later developed nephrotic syndrome. Renal biopsy of the patient was consistent with MPGN type 1, which has not been previously reported in children with coeliac disease. A gluten-free diet was started. After 6 months of this diet, her nephrotic syndrome resolved completely. This case is presented to draw attention to the rare association of coeliac disease and MPGN type 1.     

Transition of children with membranoproliferative glomerulonephritis to adolescence and adulthood

Background Many chronic renal diseases in children, including membranoproliferative glomerulonephritis (MPGN), often continue into adulthood, and these patients require continuing management. Despite the importance of the topic, there has been limited discussion about the problems of transition in children with continuing renal disease. We report our experience in patients with MPGN, as they matured from childhood to adolescence and adulthood, so-called “carry-over” cases. Methods The clinical course of diffuse MPGN in 27 children was retrospectively reviewed. Patients were over 18 years old at the end of follow-up. Results The mean follow-up period was 12.6 years; 20 children (74%) were identified by school urinary screening. The clinical course was favorable, and none of the patients progressed to end-stage renal failure during follow-up. However, eight patients (30%) continued to demonstrate proteinuria; two patients were nephrotic. Four patients were non-compliant and discontinued medication by themselves. Three patients were still on low dose of alternate-day (ALD) prednisolone. Twenty patients finished the treatment and were followed for an average of 4.6 years. Only one demonstrated trace amounts of proteinuria 1 year after discontinuing ALD prednisolone. Conclusions MPGN often continues during maturation from childhood to adulthood, and patients are usually referred to adult nephrologists. Good communication between pediatric and adult nephrologists is important. In addition, more in depth explanation and reeducation about their disease and its management are helpful when these patients reach adolescence. These measures will improve their care and help to assure compliance with their medication regimen.     

Long-term follow-up of type III membranoproliferative glomerulonephritis in children

Seven patients with type III membranoproliferative glomerulonephritis (MPGN) were followed for 9–17 years. Their mean age at presentation was 11.0 years. Their urinary abnormalities were detected by school urinary screening in five, and two patients presented with nephrotic syndrome. With time, urinalysis became normal in five, proteinuria persisted in one and nephrotic syndrome persisted in one. All had serum creatinine levels below 1 mg/dl at the last follow-up. All were initially hypocomplementemic. Serum C3 levels became normal in five patients but decreased again in three without clinical changes. Mesangial proliferation was initially slight or moderate in five but, except for one patient, histological changes persisted in follow-up biopsies even though in two the urinalysis became normal. Electron micrographic studies using silver-methenamine staining revealed subepithelial and subendothelial deposits associated with basement membrane disruption and layering of the lamina densa, an abnormality typical of MPGN type III. These observations suggest long-term outcome of type III MPGN is good despite persisting changes in type III lesions. Received: 11 July 2001 / Revised: 11 October 2001 / Accepted: 12 October 2001     

Hypocomplementaemia and membranoproliferative glomerulonephritis in school urinary screening in Japan

Yearly screening was performed from 1980 to 1985 in 92,934 school children in the first to ninth grades; a total of 370,148 urine specimens were evaluated. In 1980 and 1981, urinary abnormalities were detected in 0.23% of children examined; the detection rates at the third level of screening for proteinuria, haematuria and haematuria with proteinuria were 0.03%, 0.15% and 0.06%, respectively. The criteria for haematuria were changed from 6 to 20 red blood cells/high power field in the second screening after 1981. Between 1982 and 1985, the equivalent rates were 0.02%, 0.07% and 0.03%, respectively, and the total abnormality prevalence was 0.13%. In 19 children the serum C3 level was below 53 mg/dl; in 5 of these it was below 30 mg/dl. Of these 5 children, 4 underwent renal biopsy and were diagnosed as having membranoproliferative glomerulonephritis.     

Effect of acetylsalicylic acid and dipyridamole in primary membranoproliferative glomerulonephritis type I

Primary membranoproliferativeglomerulonephritis (MPGN) has a poor long-termprognosis, with 40 per cent of patientsreaching end-stage renal failure after 10 yearsof observation. Approximately 35 per cent ofpatients die due to complications of thenephrotic syndrome. This study investigates theeffect of acetylsalicylic acid (ASA) combinedwith dipyridamole on proteinuria and renalfunction in nephrotic MPGN patients withnormal/moderately reduced glomerular filtration rate(GFR). Fourteen patients with biopsy-proventype I MPGN received ASA (1000 mg/day) anddipyridamole (300 mg/day) for 24 months.Proteinuria was reduced from 6.8 ± 2.4 g/dayto 1.1 ± 0.6 g/day (p < 0.001). Serumalbumin levels increased from 2.2 ± 0.5 g/dLto 3.7 ± 0.4 g/dL (p < 0.001) duringthe study period after 24 months compared tobaseline. Serum creatinine and GFR did notsignificantly change in patients treated withacetylsaliclylic acid and dipyridamole duringthe observation period (p < 0.05). Ourstudy suggests that ASA combined withdipyridamole significantly reduces proteinuria without impairing renal function in patientswith MPGN.     

Cutaneous telangiectasia,sparse hair and membranoproliferative glomerulonephritis

A boy with sparse red hair, absent eye-brows and eyelashes, cutaneous telangiectasia, poorly developed subcutaneous fat and normocomplementaemic membranoproliferative glomerulonephritis is described. Additional findings were an old-looking, peculiar face, mild developmental delay, calcified choroid plexus and renal arteriolosclerosis. It is believed that this is a new case of a newly recognized entity.     

Resolution of hepatitis B virus-related membranoproliferative glomerulonephritis after orthotopic liver transplantation

The most well-described renal disease associated with hepatitis B virus (HBV) infection is membranous glomerulonephritis; membranoproliferative glomerulonephritis is described much less frequently. The course of HBV-associated renal disease after liver transplantation has not been described to date. We present a 15-year-old girl with HBV-associated membranoproliferative glomerulonephritis and end-stage liver disease, in whom, after cadaver liver transplantation, clinical and histological resolution of renal disease was observed. Resolution was associated with diminution of circulating HBV surface antigen levels.     

Rheumatoid arthritis and membranoproliferative glomerulonephritis: an unusual case

SUMMARY: Renal involvement is not uncommon in rheumatoid arthritis (RA). Many RA patients have renal dysfunction either secondary to the drugs used to treat arthritis or because of the chronic inflammation. Renal pathologies have often included amyloidosis, drug-related renal disease and mesangial glomerulonephritis. However, membranoproliferative glomerulonephritis has only been rarely reported. We report a case of rheumatoid arthritis associated with membranoproliferative glomerulonephritis that rapidly progressed to end-stage renal disease.