Postpartum renal failure in a patient with membranoproliferative glomerulonephritis type II

The previously reported detrimental effects of pregnancy on the course of membranoproliferative glomerulonephritis type II (MPGN type II) are limited and are usually considered to be mild. Based on these reports, a 19-year-old female with the diagnosis of MPGN type II who had stable renal function (creatinine 0.9 mg/dl) and a mild nephrotic syndrome with hypertension for 5 years of close follow-up was advised to complete her pregnancy. After a full-term pregnancy, complicated only by moderate nephrotic syndrome, a healthy female infant was born. Two weeks after delivery, the patient presented with acute renal failure and malignant hypertension, without evidence of hemolysis of hepatic failure. Immunologic parameters, including, C3, C4, antinuclear antibodies, circulating immune complexes as well as antibodies to glomerular basement membrane antigen and tubular basement membrane antigen were negative. Peritoneal dialysis was initiated and a renal biopsy was performed which showed MPGN type II with 50% crescents. Despite pulse therapy with methylprednisolone, renal function did not improve, resulting in the need for chronic dialysis. Although no specific nephritogenic mechanism was shown, the course of this patient should be considered when counseling female patients with MPGN type II, regarding the possibility of pregnancy exacerbating their disease, or resulting in rapidly progressive renal failure.     

Successful pregnancy in primary glomerular disease

The course of 66 pregnancies was studied in 48 women with primary glomerular diseases. In all cases diagnoses were established by biopsy before pregnancy. They were: membranoproliferative glomerulonephritis in 16 patients, focal glomeruloesclerosis in 13, IgA nephropathy in 10, membranous nephropathy in seven and focal glomerulonephritis in two women. The clinical status of the nephropathy before conception was that 43 had only mild renal dysfunction, five had moderate renal insufficiency, serum creatinine (1.3 to 1.9 mg%), eight women had hypertension (150/100 mm Hg) and eight had nephrotic range proteinuria. Their clinical course was compared with a control group of 36 women with primary glomerular disease who did not become pregnant, and were matched for similar age, histological type, and status of nephropathy (renal function, blood pressure and proteinuria). After one year and at the end of the five year follow-up period, the incidence of hypertension, proteinuria, and renal failure was similar in the two groups. The fetal survival rate was 92%; 51 pregnancies ended in full-term delivery, with a mean birthweight of 3,242 +/- 320 g. There were seven pre-term deliveries (2,170 +/- 135 g), three small for gestational-age (2,340 +/- 135 g), two stillbirths and three spontaneous abortions. These patients had more pre-term deliveries (10.6%) and perinatal mortality (31%) than a normal population (5.5% and 9.6%, respectively). Blood pressure increased during pregnancy in 13 women; in 10 it was reversible, and in four it persisted after delivery. Ten gravidas developed increased proteinuria (reversible in six of them) and two others developed permanent impairment of renal function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spontaneous clinical improvement in dense deposit disease

The clinical course and 3-year follow-up of a female patient aged 11 years who presented with nephrotic syndrome and renal failure is described. The renal biopsy revealed type II membranoproliferative glomerulonephritis or dense deposit disease. She was treated with penicillin prophylaxis, frusemide and captopril, and was not given immunosuppression, anticoagulation or antiplatelet therapy. Despite poor prognostic clinical and pathological features, she had spontaneous resolution of her renal failure and proteinuria, although her proteinuria recurred 17 months post presentation. Her unusual progress, with improvement in her disease activity and normalisation of her glomerular filtration rate, is described. Received: 7 August 1998 / Revised: 13 July 1999 / Accepted: 14 July 1999     

Rapidly progressive glomerulonephritis (crescentic glomerulonephritis) in the course of type I idiopathic membranoproliferative glomerulonephritis

Membranoproliferative glomerulonephritis is a chronic glomerulopathy with a generally progressive course toward end-stage renal disease and a high recurrence rate in renal allografts. Described herein is the appearance of rapidly progressive glomerulonephritis (crescentic glomerulonephritis) in the course of type I membranoproliferative glomerulonephritis. This transition occurred within 6 weeks, documented histologically by an initial and subsequent renal biopsy. No recurrence of the disease was noted in a living donor graft 18 months posttransplantation.     

Hepatitis C virus-associated glomerular disease in patients with human immunodeficiency virus coinfection.

Chronic infection with hepatitis C virus (HCV) has been linked to the development of glomerular disease. HCV infection is highly prevalent among intravenous drug users, a population that is also at risk for HIV coinfection. This study reports the clinical-pathologic features and outcome of HCV-associated glomerular disease (HCV-GD) in 14 patients with HIV coinfection. All were intravenous drug users and all but one were African-Americans. Renal presentations included renal insufficiency, microscopic hematuria with active urine sediment, hypertension, and nephrotic syndrome or nephrotic-range proteinuria without hypercholesterolemia. Hypocomplementemia and cryoglobulinemia were present in 46 and 33% of patients, respectively. The predominant renal biopsy findings were membranoproliferative glomerulonephritis type 1 or type 3 (Burkholder subtype) in 79% of patients and membranous glomerulopathy with atypical features in 21% (including overlap with collapsing glomerulopathy in one patient). The clinical course was characterized by rapid progression to renal failure requiring dialysis. The overall morbidity and mortality were high with median time of 5.8 mo to dialysis or death. Although most patients died in renal failure, cause of death was primarily attributable to long-term immunosuppression and advanced AIDS. Patients with AIDS had shorter survival than those without (median survival time of 6.1 mo versus 45.9 mo, log-rank test P = 0.02). Only two patients were alive with stable renal function at follow-up of 28.5 mo. In patients with HCV-GD, coinfection with HIV leads to an aggressive form of renal disease that can be easily confused with HIV-associated nephropathy. Although hypocomplementemia, cryoglobulinemia, and more prominent hypertension and microscopic hematuria may provide clues to the presence of HCV-GD, renal biopsy is essential to differentiate HCV-GD from HIV-associated nephropathy.     

Effective treatment of hepatitis C-associated immune-complex nephritis with cryoprecipitate apheresis and antiviral therapy

A 38-year-old pregnant woman (19th week of pregnancy) complained of fatigue, cold inducible paresthesias, generalized edema and mild arterial hypertension. Her past medical history was notable for frequent episodes of polyarthralgia and positivity for rheumatoid factor. On admission, acanthocyturia and unselective glomerular-tubular proteinuria with 19 g/d were detected with a slight decrease in creatinine clearance. Rheumatoid factor was robustly elevated and a cryocrit of 1.5 vol%, caused by a so far unknown replicative hepatitis C, was detected. Renal biopsy yielded membrano-proliferative glomerulonephritis. During pregnancy, high-dose corticosteroid therapy was administered. Edema disappeared and blood pressure normalized under albumin substitution and low-dose furosemide application. However, Cesarian section became necessary due to placental insufficiency at 27 weeks of gestation. Thereafter, neither virus load, cryocrit nor proteinuria decreased significantly under a combined therapy with pegylated interferon-a and ribavirin. Thus, cryoprecipitate apheresis was initiated resulting in robust decreases of clinical complaints, viral load, cryocrit and proteinuria. Cryoglobulinemia with renal involvement caused by hepatitis C is difficult to treat due to limitations of immunosuppressive and anti-viral therapy. In our patient, cryoprecipitate apheresis was a safe and effective therapeutic addition to standard therapy.     

De novo membranoproliferative glomerulonephritis III in a renal transplant patient: case report and review of the literature

Idiopathic membranoproliferative glomerulonephritis (MPGN) is a rare cause of renal failure with a cumulative incidence of 0.3% of all ESRD and 4% of all primary glomerulonephritis for types I and II. Membranoproliferative glomerulonephritis type III is more uncommon and idiopathic de novo MPGN III in a renal transplant patient has not been reported. We present the case of a 57-year old white female patient with a diagnosis of lithium toxicity as cause of end stage renal disease (ESRD) who developed MPGN III in her allograft 6 years after a renal transplant. Despite treatment, she progressed to ESRD within four and a half years from the time of diagnosis.     

Recurrence of fibrillary glomerulonephritis in a renal transplant recipient

Fibrillary glomerulonephritis (FGN) is a rare glomerular deposition disease and a rare cause of nephrotic syndrome. The patients usually present with renal insufficiency, nephrotic range proteinuria and microscopic hematuria. The electron microscopy study is the only means of diagnosis. The clinical course of the disease is generally unpredictive and the patients inevitably progress to ESRD. Here, we describe a case of FGN, which presented with nephrotic syndrome and impaired renal function. Renal biopsy showed that 26 out of 30 glomeruli were completely sclerosed. Remaining showed mesangial expansion and double contour consistent with a membranoproliferative pattern, with 70 % interstitial fibrosis and tubular atrophy. Immunofluorescence revealed C3 (2+) diffuse mesangial deposits. Electron microscopic showed subendothelial dense deposits with organized tubular structures. During follow-up, the patient underwent renal transplantation from a living unrelated kidney donor. Later on, as the renal allograft function showed deterioration, renal biopsy was performed and showed recurrence of FGN in the renal allograft.     

Dense intramembranous deposit disease: new pathologic features

The pathologic and clinical features of 16 patients with dense intramembranous deposit disease are described. By light microscopy nine patients had membranoproliferative glomerulonephritis, five had focal segmental necrotizing glomerulonephritis with segmental epithelial crescents, four of whom also had a prominent tubulointerstitial nephritis, and two had focal segmental mesangial proliferative glomerulonephritis. The patients with membranoproliferative glomerulonephritis and one with focal segmental mesangial proliferative glomerulonephritis had easily recognizable dense intramembranous deposits by optical microscopy. The patients with focal segmental necrotizing glomerulonephritis and one with focal segmental mesangial proliferative glomerulonephritis did not have recognizable peripheral loop dense intramembranous deposits even under oil immersion. In patients with membranoproliferative glomerulonephritis ultrastructural examination revealed extensive capillary wall dense intramembranous deposits. Immunofluorescence revealed diffuse double linear staining along the capillary walls and "mesangial rings" of C3. In the patients with focal segmental necrotizing glomerulonephritis and one with focal segmental mesangial proliferative glomerulonephritis the immunofluorescence study suggested a diagnosis of dense intramembranous deposit disease because of the segmental double linear staining of the capillary walls and "mesangial rings" of C3, but the diagnosis was only established by fine structural analysis where occasional peripheral loop and prominent paramesangial basement membrane dense intramembranous deposits and mesangial nodular deposits were identified. Clinical features prior to biopsy included nephrotic syndrome in eight patients, an acute nephritic syndrome in six patients, and asymptomatic proteinuria and hematuria in two patients. Five of six patients with an acute nephritic presentation had focal segmental necrotizing glomerulonephritis. The acute renal insufficiency in these patients was transitory and appeared to be related to a prominent acute tubulointerstitial nephritis present in four of the biopsy specimens. Depressed serum C3 levels were present in patients with membranoproliferative glomerulonephritis; patients with focal segmental lesions were normocomplementemic. Because of the "atypical" light microscopic features in six of our patients, we support the suggestion that membranoproliferative glomerulonephritis, type II be replaced by the term 'dense intramembranous deposit disease' for this glomerulopathy with variable clinical and histologic features.     

Renal transplantation and schistosomiasis mansoni

Eleven patients with schistosomiasis mansoni received a renal transplant. In 5 patients, the schistosomiasis was asymptomatic and had been diagnosed by routine examinations and had no relationship to nephropathy. In 4 patients, the nephropathy was suggestive of being of schistosomal origin. Three of them had symptomatic hepatosplenic schistosomiasis, and histologic studies of original kidneys disclosed chronic glomerulonephritis in 2 and membranous glomerulonephritis in 1 patient. These histologic pictures do not establish definitively the schistosomal origin of nephropathy. The other patient had membranoproliferative glomerulonephritis that recurred in the allograft, but he had intestinal schistosomiasis. This form of the disease is not considered by all as capable of inducing nephropathy. Two patients had the hallmarks of schistosomal nephropathy: hepatosplenic form and membranoproliferative glomerulonephritis. The 1st patient developed nephrotic syndrome 3 years after the transplantation, and an allograft biopsy disclosed membranoproliferative glomerulonephritis. The other patient had an uneventful outcome with good renal function and no proteinuria. An allograft biopsy performed 14 months after the transplant disclosed slight mesangial proliferation with IgM++ and C3++ in the mesangium.     

Influences of pregnancy on the natural course of chronic glomerulonephritis with impaired renal function]

In an attempt to clarify the influence of pregnancy on the natural course of the chronic glomerulonephritis with impaired renal function (glomerular filtration rate: GFR less than or equal to 70 ml/min), the courses of 14 pregnancies occurring in 10 patients (seven with IgA nephropathy, one with membranoproliferative glomerulonephritis, one with membranous nephropathy and one with hereditary nephropathy) were studied. In 8 patients GFR measured before pregnancies ranged from 46 to 70 ml/min and in the other two creatinine clearance estimated in the first trimester of pregnancies was 62 and 49 ml/min, respectively. The pregnancies resulted in 10 live births, one spontaneous abortion, one artificial abortion and 2 neonatal deaths. In 2 out of 10 live births fetal weight was less than 2500 g. In 3 of 11 pregnancies there was neither increase in urinary protein nor elevation of blood pressure during pregnancies, while seven (64%) had increased proteinuria during the third trimester, and 4 of them were also complicated with hypertension. In 6 of 10 patients, there was no decrease in GFR during pregnancies. In three patients GFR was decreased from 70 to 36 ml/min, 70 to 58 ml/min and 62 to 48 ml/min, respectively. However, these reductions were considered to go with the natural course of respective patients because the reduction slopes were almost the same or rather mild in comparison with those estimated before or after pregnancies. The other patient also had a transient increase in serum creatinine level during two pregnancies, but the reciprocals of serum creatinine concentration before and after the pregnanciesdeclined linearly with time. These data suggest that pregnancy might have little influence on the natural course of the chronic glomerulonephritis even if complicated with renal functional impairment defined as GFR of 70 ml/min or less.     

Idiopathic lobular glomerulonephritis (nodular mesangial sclerosis): a distinct diagnostic entity

Lobular glomerulonephritis is an entity first thought to have represented a primary disease of uncertain histogenesis, but more recently has generally been considered to represent a morphologic variant of membranoproliferative glomerulonephritis. We have encountered five patients who were found to have a lobular glomerulonephritis by renal biopsy, but in whom features of membranoproliferative glomerulonephritis types I, II, or III, could not be demonstrated and in whom alternate known diagnostic categories could be excluded. We suggest that lobular glomerulonephritis, or alternately, idiopathic nodular mesangial sclerosis, is an uncommon but persistent disease entity with a distinctive pathologic appearance and unknown pathogenesis.     

An overview of pregnancy in women with underlying renal disease

This is a report of a retrospective study of the effects of preexisting glomerular disease and pregnancy on each other. Two hundred forty pregnancies in 166 Japanese women who delivered between 1970 and 1988 were analyzed. There were 206 (86%) live births, 14 (6%) perinatal deaths, and 20 (8%) spontaneous abortions. Perinatal loss was greatest in women with hypertension and/or glomerular filtration rate (GFR) less than 70 mL/min before conception. Pregnancy did not appear to adversely affect the underlying glomerular disease if GFR was greater than 70 mL/min and blood pressure was below 140/90 mm Hg. However, with moderately impaired renal function (creatinine greater than 124 mumol/L [1.4 mg/dL] or GFR less than 50 mL/min), the long-term prognosis was poorer, despite generally favorable obstetrical outcomes. Gravidas with membranoproliferative glomerulonephritis had the highest rates of hypertension (29%) and decreased renal function (33%) at final follow-up, ie, the type and severity of glomerulonephritis had a major impact on clinical course.     

Hypertension in primary chronic glomerulonephritis: analysis of 288 biopsied patients

The prevalence of hypertension in 288 patients with primary chronic glomerulonephritis was compared with that observed in a control group of 3,477 subjects from the same geographic area. 23.3% of the patients and 12.8% of the general population were hypertensive (p less than 0.01). However, if only patients with normal renal function were considered, prevalence of hypertension (12.7%) was not higher than in the control group. Hypertension was more frequent in focal segmental sclerosis (30%) and in membranous glomerulonephritis (26%) than in IgA nephropathy (9%), membranoproliferative glomerulonephritis (11%) and IgM mesangial glomerulonephritis (12%). Five years after renal biopsy, 92% of normotensive and 47% of hypertensive patients remained with normal renal function (p less than 0.001). These findings suggest that the high prevalence of hypertension in chronic glomerulonephritis is related to the declining renal function. On the other hand, hypertension appears to represent a bad prognostic sign.     

Nephropathy associated with heroin abuse in Caucasian patients.

BACKGROUND: Renal disease is a complication of heroin addiction. Using renal biopsies in Caucasian patients, we studied the types of nephropathy associated with heroin abuse. METHODS: Nineteen renal biopsies were performed on heroin addicts between January 1993 and December 2001. The indications for renal biopsy included proteinuria with or without renal insufficiency. RESULTS: All 19 patients had serological evidence of hepatitis C virus (HCV) infection, one had hepatitis B virus surface antigen and three were HIV positive. Thirteen patients (68.4%) were found to have membranoproliferative glomerulonephritis (MPGN), 12 with type I and one with type III. Of the remaining patients, two had chronic interstitial nephritis, two had acute proliferative glomerulonephritis, one had amyloidosis and one had granulomatous glomerulonephritis with interstitial nephritis. No apparent decline in the incidence of renal disease was observed. CONCLUSIONS: In this cohort of male Caucasian heroin addicts, HCV-associated MPGN was the most frequent pattern of nephropathy, showing that the nephropathy associated with heroin abuse in Caucasians is not of the focal and segmental glomerulosclerosis type, in contrast to previous reports on African-Americans. This aspect may have important implications for patient management and prognosis.     

Long-term follow-up of type II membranoproliferative glomerulonephritis in two children

We report the long-term follow-up of two patients with type II membranoproliferative glomerulonephritis (MPGN). One Patients was treated with high-dose alternate-day prednisolone and the other with dipyridamole. Both had favorable clinical courses over 8.5 and 15.5 years of follow-up, respectively. One patient who showed diffuse proliferative changes lost the urinary abnormalities 2 years after starting treatment. Her follow-up renal biopsies showed histological improvement. In the other patient, a boy, renal biopsy performed 6 years after the onset showed mild mesangial proliferation and a moderate matrix increase. His urine became normal 14 years after onset. Intramembranous electron-dense deposits persisted in these patients over 7 and 6 years of observation, respectively. Patients with type II MPGN are usually difficult to treat and often progress to endstage renal failure. There is, however, a group of patients who have a favorable clinical course. Received: June 20, 2002 / Accepted: November 18, 2002 Acknowledgments The authors wish to express their gratitude to Dr. Nobuo Matsuura for reviewing this article. Correspondence to:K. Iitaka     

Childhood membranoproliferative glomerulonephritis type I: limited steroid therapy.

Nineteen patients with biopsy proven membranoproliferative glomerulonephritis type I (MPGN I) and a minimum of three years of follow-up (mean 6.5 +/- 0.7 years) have been treated with an uncontrolled regimen of limited corticosteroids. Initial therapy ranged from 20 mg per os (po) every other day to 30 mg/kg/day i.v. for three consecutive days, depending on clinical disease severity. Therapy was then decreased based on each patient's improving clinical status. At diagnosis creatinine clearance (CCr) was less than 80 ml/min/1.73 m2 in 12 patients and less than 50 in 2. All patients had hematuria and proteinuria, with 15 in the nephrotic range. Hypertension, present at diagnosis in 13, developed in five others following institution of prednisone, and was controlled medically. Renal biopsy was repeated after two years of therapy prior to cessation of treatment (mean total treatment duration 38 +/- 3 months). Follow-up biopsy revealed decreased glomerular inflammatory activity in 88% of patients. All patients have now been off prednisone for 40 +/- 9 months. The mean CCr is 126 +/- 5 ml/min/1.73 m2. Eight patients have normal urinalyses. These data suggest that early therapy with a limited course of corticosteroids, and control of associated hypertension, may forestall progressive renal insufficiency in children with MPGN type I.     

Other glomerular pathologies in three patients with diabetes mellitus

Diabetic nephropathy is the common cause of end stage renal disease in diabetes mellitus. But other glomerular pathologies have been also described in diabetic patients. We described 3 cases with diabetes mellitus and other glomerular diseases. Case I: A 59-year-old male patient with type 2 diabetes mellitus for 4 years was evaluated for generalized edema. Physical examination showed pretibial edema and no diabetic retinopathy. The cause of nephrotic syndrome was membranoproliferative glomerulonephritis. Conservative therapy could not control the severe proteinuria and renal dysfunction. With corticosteroid and cyclophosphamide therapy partial remission was obtained. Case II: A 46-year-old diabetic woman was evaluated for severe proteinuria. Diabetic retinopathy was not found on her funduscopic examination. Mesangioproliferative glomerulonephritis was found on renal biopsy. Proteinuria did not regress with conservative therapy and corticosteroid and cyclophosphamide. Case III: A 48-year-old male patient with diabetes mellitus type 2 for 2 years was admitted to the hospital because of nephrotic syndrome and weakness. At another hospital his diagnosis with biopsy showed minimal change disease. He was treated with corticosteroid since 3 months. His renal biopsy was reevaluated and found amyloid deposition but not diabetic nephropathy or minimal change disease. In diabetic patients, nondiabetic nephropathy is not uncommon and it was reported as common as about 30%. In addition to therapy for diabetes mellitus these patients can need specific therapy.     

Membranoproliferative glomerulonephritis following allogeneic hematopoietic stem cell transplantation

Nephrotic syndrome after allogeneic hematopoietic stem cell transplantation has been increasingly described as a manifestation of chronic graft-versus-host disease (GVHD); however, GVHD-associated membranoproliferative glomerulonephritis is extremely rare. A 44-year-old man developed nephrotic syndrome 24 months after HSCT for acute lymphoblastic leukemia. The renal biopsy showed type I membranoproliferative glomerulonephritis. Salivary gland biopsy demonstrated mild lymphocytic infiltration, indicating chronic GVHD. Improvement of the proteinuria and recovery of renal function were achieved within 11 months of treatment with oral prednisolone and azathioprine.     

Membranoproliferative glomerulonephritis associated with multicentric angiofollicular lymph node hyperplasia. Case report and review of the literature.

A 14-year-old boy presented with fever, anemia, hepatosplenomegaly, generalized lymphadenopathy and nephrotic syndrome. Lymph node biopsy showed angiofollicular lymph node hyperplasia (generalized Castleman's disease) of the plasma cell type. Kidney biopsy showed membranoproliferative glomerulonephritis type 1. Complete remission was achieved with corticosteroid treatment and repeat kidney biopsy 22 months later showed complete resolution of the renal pathology. The association between membranoproliferative glomerulonephritis and multicentric angiofollicular lymph node hyperplasia, plasma cell type, has not previously been reported.