Pattern of double glomerulopathy in children

Occasional case reports have been issued on children with double glomerulopathy, involving either the coexistence of two different glomerulopathies or superimposition of a second glomerulopathy onto a first. A retrospective clinicopathological review of 294 children who had received renal biopsies resulted in 9 (3.1%) being confirmed to have double glomerulopathy. Superimposed glomerulopathy was diagnosed by a second renal biopsy in two cases, and coexistence of two glomerulopathies was confirmed by single biopsy in seven. Original glomerulopathies were those with a chronic course, such as Alport syndrome, IgA nephropathy, relapsing minimal-change nephrotic syndrome, Frasier syndrome, and thin basement membrane nephropathy. The superimposing glomerulopathies were common types in children, such as postinfectious glomerulonephritis, IgA nephropathy, and Henoch-Schönlein nephritis. Thus, the pattern of double glomerulopathy was considered to be due to the chance occurrence of two different glomerulopathies without a common pathogenesis. Acute nephritic symptoms of superimposed glomerulopathies resolved almost completely during follow-up in most cases. Double glomerulopathies are not rare in children and may occur by chance alone in most cases. The possibility of superimposed glomerulopathy should be suspected if the clinical course of a glomerulopathy changes atypically. However, the long-term influence of a superimposed glomerulopathy on renal functional deterioration remains unclear.     

Immunotactoid glomerulopathy with microtubular deposits, with reference to the characteristics of Japanese cases

We present the case of a 69-year-old man with nephrotic syndrome and renal insufficiency, who developed lobular glomerulonephritis. An electron microscopy examination of a renal biopsy showed microtubular structures of 24 nm in diameter in the subendothelial space and the paramesangial area. These deposits were PAS-positive and Congo red-negative, and revealed predominantly positive staining for kappa light chain. There was no evidence of diseases with highly organized glomerular deposits, such as amyloidosis, cryoglobulinemia, systemic lupus erythematosus or paraproteinemia. Therefore, the patient was diagnosed to have immunotactoid glomerulopathy (ITG). During a seven-year course he has not developed any disease known to be associated with organized glomerular immune deposits. Hence, we believe ITG occurred as a primary glomerular disease in this case. We also highlight cases of ITG with microtubular deposits that have been reported in Japan, compare these cases to previous reports, and show that the characteristics of the Japanese cases are male predominance; a high incidence of membranoproliferative glomerulonephritis (MPGN); a low incidence of monoclonal gammopathy and hematological malignancies and a higher incidence of hypocomplementemia.     

Acute renal failure at the onset of idiopathic nephrotic syndrome in two children

Two children with idiopathic nephrotic syndrome (INS) developed acute renal failure (ARF) at the onset of the disease. Although the initial renal biopsy showed minimal change (MC) lesions with prominent interstitial edema, repeat renal biopsy revealed focal segmental glomerulosclerosis (FSGS). ARF has been reported to be a relatively rare complication in childhood INS. However, the initial manifestation of ARF may increase the risk for subsequent progression to FSGS in a proportion of children with INS with MC lesions. Received: April 3, 2000 / Accepted: October 31, 2000     

Prognosis of the nephrotic syndrome in sickle glomerulopathy. A retrospective study

Of 240 adults with sickle cell anemia seen over 11 years, 12 had the nephrotic syndrome. In 9 (75%) the glomerular lesion, sickle glomerulopathy, consisted of mesangial expansion and basement membrane duplication. Six patients had type IV renal tubular acidosis. Four of the 9 Patients died within 24 months (17 +/- 5; mean +/- SD), while 5 survived 36 months or longer (80 +/- 49); no significant differences were seen between the former and the latter in age, admission serum creatinine and C3 levels, urinary protein excretion, or the frequency of renal tubular acidosis. Chronic azotemia developed in 3 and acute renal shutdown in another 2. Of 22 patients with sickle glomerulopathy (our 9 added to 13 from the literature) 11 died within 2 years. Ten of these (91%) had developed renal failure, compared to only 5 of the 11 (45%) who survived longer than 2 years (p less than 0.05). The 5-year mortality in the general population of sickle cell anemia is 3.75%, and 75% of patients aged 15 years or older survive 18 years or longer. The nephrotic syndrome, most often caused by sickle glomerulopathy, occurs in 4% of patients with sickle cell anemia, leading to renal failure in two-thirds and death in 2 years in half the patients. The development of chronic azotemia correlates strongly with early mortality. The prognosis is much worse than that in the general population of sickle cell anemia.     

Fibrillary glomerulopathy in a 10-year-old female

A 10-year-old African-American female was evaluated for asymptomatic proteinuria. Initial investigation did not reveal the etiology of her renal disease. She subsequently underwent a percutaneous renal biopsy, which was consistent with fibrillary glomerulopathy. This condition is rare in children and is identified histologically by a solid, randomly arranged, amyloid-like fibrillar structure with a diameter of about 18–22 nm. It is a diagnosis of exclusion, the clinical presentation of which can be quite varied. Children usually present with nephrotic syndrome. There is no effective therapy for this condition. Therapy with steroids, cytotoxic agents, and plasmapheresis does not confer any real benefit in stabilizing or improving renal function. However, angiotensin converting enzyme inhibitors can decrease the proteinuria. End-stage renal disease is known to occur in 50% of patients within 4 years of diagnosis. The nephrotic-range proteinuria in our patient significantly decreased during a 4-year follow-up without any therapy, while maintaining normal renal function. Received: 4 April 2001 / Revised: 13 June 2001 / Accepted: 30 June 2001     

Membranous glomerulopathy associated with graft-versus-host disease following allogeneic stem cell transplantation. Report of 2 cases and review of the literature.

We report two cases of nephrotic syndrome presenting 18 and 20 months after allogeneic stem cell transplantation (alloSCT) with chronic myelogenous leukemia. Both patients had acute and chronic graft-versus-host disease (GVHD) and renal biopsy findings of membranous glomerulopathy (MG). A review of the literature revealed 10 additional cases of immune-complex-mediated glomerular disease following alloSCT, 8 of which were diagnostic of MG. All patients showed evidence of acute or chronic GVHD. Patients typically presented with preserved renal function (mean creatinine 1.2 mg/dl) and full nephrotic syndrome including heavy proteinuria (mean 9.2 g/24 h), edema, hypoalbuminemia (mean 2.1 g/dl) and hypercholesterolemia (mean 472 mg/dl). Most patients showed stabilization of renal function and significant decreases in proteinuria when treated with steroids and/or cyclosporine. The close temporal association as well as evidence from murine models of GVHD support a pathogenetic association between GVHD and the development of MG.     

Glomerular diseases in children. "The Iranian experience"

A total of 411 children, aged from 0.3 to 18 years, suffering from glomerular diseases, were studied by renal biopsy between 1976 and 1985. The clinical presentation included nephrotic syndrome (79% of cases), renal failure (43%), and arterial hypertension (38%). In all, 177 cases presented with primary nephrotic syndrome; all had complicated courses and most were either corticosteroid-dependent or -resistant. Only 26.6% had minimal change disease on renal biopsy; 56.5% had focal-segmental sclerosis; and immunofluorescent deposits were observed in half of the group. Acute poststreptococcal (36 cases), mesangiocapillary (80 cases), and lupus (34 cases) glomerulonephritis occurred frequently; IgA glomerulopathy (10 cases) and haemolytic uraemic syndrome (6 cases) were uncommon. Glomerular crescents were observed in 71 cases. These observations illustrate the types of glomerular diseases seen in Iranian children.     

Glomerular diseases in children

A total of 411 children, aged from 0.3 to 18 years, suffering from glomerular diseases, were studied by renal biopsy between 1976 and 1985. The clinical presentation included nephrotic syndrome (79% of cases), renal failure (43%), and arterial hypertension (38%). In all, 177 cases presented with primary nephrotic syndrome; all had complicated courses and most were either corticosteroid-dependent or-resistant. Only 26.6% had minimal change disease on renal biopsy; 56.5% had focal-segmental sclerosis; and immunofluorescent deposits were observed in half of the group. Acute poststreptococcal (36 cases), mesangiocapillary (80 cases), and lupus (34 cases) glomerulonephritis occurred frequently; IgA glomerulopathy (10 cases) and haemolytic uraemic syndrome (6 cases) were uncommon. Glomerular crescents were observed in 71 cases. These observations illustrate the types of glomerular diseases seen in Iranian children.     

Angiotensin converting enzyme gene polymorphisms do not predict the course of idiopathic nephrotic syndrome in Swiss children

AIM: Contradictory reports exist about a correlation of angiotensin I converting enzyme (ACE) gene polymorphisms to the outcome of idiopathic nephrotic syndrome (INS) in children. We investigated the frequency of ACE polymorphisms and their impact on the clinical course of INS in children in a Swiss hospital. METHODS: The ACE gene polymorphism (I, insertion; D, deletion) was assessed in 32 children - 22 with steroid-sensitive INS and 10 with steroid-resistant INS - with a median age at onset of INS of 2.9 years (range 1.1-15.0). Polymerase chain reaction amplification was performed on genomic DNA isolated from blood leucocytes. Results were correlated to clinical course and renal morphology. RESULTS: The ACE genotype was I/I, I/D and D/D in two, 12 and eight patients, respectively, with steroid-sensitive INS, and in one, eight and one patient, respectively, with steroid resistance. Renal morphology, available in 25 patients showed minimal change glomerulopathy in 17 patients (14 steroid-sensitive; three steroid-resistant) and focal segmental glomerulosclerosis in eight (one steroid-sensitive; seven steroid-resistant). There was no significant correlation between ACE genotype and steroid responsiveness, histology or outcome. ACE genotype was I/I, I/D and D/D in none, 12 and five patients, respectively, with minimal change glomerulopathy, and in one, five and two patients, respectively, with focal segmental glomerulosclerosis. Six patients with steroid-resistant nephrotic syndrome went into end stage renal disease; ACE genotype was I/I in one and I/D in five, but none were D/D. CONCLUSION: In contrast to previous reports, ACE gene polymorphism is irrelevant for clinical outcome, steroid responsiveness or morphology in Swiss children with INS.     

Crescentic membranoproliferative glomerulonephritis and hypocomplementemic urticarial vasculitis

We describe the association of crescentic membranoproliferative glomerulonephritis and hypocomplementemic urticarial vasculitis syndrome. A 39-year-old woman presented edema and proteinuria and later a non-pruritic urticarial rash. Laboratory results showed nephrotic syndrome, hypocomplementemia and positive anti-C1q antibodies. Skin biopsy disclosed leukocytoclastic vasculitis. Acute renal failure developed. Renal biopsy revealed crescentic membranoproliferative glomerulonephritis. She was treated with corticosteroids and cyclosphosphamide with improvement of the renal function and partial remission of the nephrotic syndrome. Afterwards the nephrotic syndrome relapsed, mycophenolate mofetil in monotherapy was administered with reduction in proteinuria. As far as we know only 3 cases, 2 in children and one in an adult, of crescentic glomerulonephritis and hypocomplementemic urticarial vasculitis syndrome have been reported. In our patient renal manifestations preceded urticarial lesions. We provide information on the evolution during a 42-month follow-up.     

Management of steroid-sensitive nephrotic syndrome in children with type 1 diabetes

Four children with steroid-sensitive nephrotic syndrome (SSNS) coexisting with type 1 diabetes are presented. This number is higher than expected according to the estimated prevalence rates for each disease separately. In three, diabetes preceded nephrotic syndrome (NS), and in one it developed almost simultaneously. None of the patients had hypertension or retinopathy. Two had a renal biopsy: in one it was compatible with minimal change histology (MCH), and the other had MCH and early diabetic nephropathy changes. In addition to the two presented here, in 11 of 12 previously reported cases with biopsy proven SSNS coexisting with type 1 diabetes, the biopsy showed MCH. In none was treatment influenced by biopsy results. However, our experience suggests that daily steroid taper allows easier glycaemic control than alternate day steroids. We conclude that the indications for a renal biopsy in nephrotic children with and without insulin-dependent diabetes mellitus (IDDM) should be similar. Received: 27 July 2001 / Revised: 15 January 2002 / Accepted: 15 January 2002     

Fibrillary-immunotactoid glomerulopathy with renal deposits of IgAlambda: a rare cause of glomerulonephritis

We describe a 24-year-old patient who presented with a nephrotic syndrome. His renal biopsy revealed a diffuse mesangioproliferative glomerulonephritis with eosinophilic deposits. Electron microscopy showed organized, Congo-red negative deposits, forming microtubules of about 20 nm width in the capillary walls and in the mesangium, establishing a diagnosis of fibrillary-immunotactoid glomerulopathy. Fibrillary-immunotactoid glomerulopathy is a rare cause of glomerulonephritis, characterized by Congo-red-negative glomerular deposits of fibrils, sometimes organized in microtubules, predominantly containing IgG and C3. Patients clinically present with the nephrotic syndrome, hematuria and hypertension. The pathogenesis of this glomerulopathy has not been elucidated yet. In our patient, the renal deposits contained IgAlambda. This peculiar feature is suggestive of an underlying paraproteinemia. However, in the serum no paraproteins or cryoglobulins were found, and also microscopical examination and immunophenotyping of the bone marrow did not point to the presence of a monoclonal plasma cell dyscrasia. Our patient was not treated with immunosuppressive drugs and he is currently progressing to end-stage renal disease.     

Paucity of minimal-change lesion in children with early frequently relapsing steroid-responsive nephrotic syndrome

It is widely believed that the most common morphological lesion in children with the idiopathic nephrotic syndrome who manifest a frequently relapsing steroid-responsive course is the minimal-change lesion. However, there are no prospective renal biopsy studies in such patients to substantiate this assertion. We performed a renal biopsy in all children with early frequently relapsing steroid-responsive nephrotic syndrome during the years 1980-1984. In 16 affected children, only 4 (25%) had minimal-change lesion, 7 had IgM nephropathy, 3 had diffuse mesangial hypercellularity, and 2 had focal segmental glomerulosclerosis. Fourteen of these patients have required immunosuppressive therapy with cyclophosphamide. Long-term follow-up revealed that 10 patients have remained protein free, 4 have persistent proteinuria despite cyclophosphamide therapy, 1 had progressed to end-stage renal disease, and 1 is lost to follow-up. On the basis of these findings, we recommend that all children with nephrotic syndrome and an early frequently relapsing steroid-responsive course undergo a prompt renal biopsy. Such patients constitute a high-risk group with a spectrum of renal histopathological lesions characterized by an unpredictable response to therapy and an unfavorable prognosis.     

AIDS-related glomerulopathy: occurrence in specific risk groups

The histopathology and incidence of AIDS-related glomerulopathy was evaluated by renal biopsy (N = 24) or at autopsy in 159 patients, including 131 adults and 28 infants and children with AIDS. Thirty-five patients had overt clinical manifestations of renal disease characterized by a nephrotic syndrome with focal and segmental glomerular sclerosis (FSS). Fifteen patients had diffuse glomerular mesangial hyperplasia (MH) without or with minimal clinical renal disease and 109 had intact or minimally involved glomeruli. Whereas 15 of 30 (50%) i.v. drug users with AIDS had evidence of renal disease, only one of 53 (2%) homosexuals had clinical renal disease and only 6 (11%) had histologic evidence of glomerular pathology. The study confirms the important risk of i.v. drug use as a pathogenic factor of renal disease and shows a rarity of renal disease in homosexual or bisexual men with AIDS. On the other hand, 30% of adult Haitians with AIDS had FSS or diffuse MH, although i.v. drug use is not an important risk factor in this population. Moreover, eight of 28 (29%) children with perinatal AIDS had evidence of renal involvement, including four with a nephrotic syndrome and FSS. The data provide strong evidence for the existence of an AIDS-related glomerulopathy independent of i.v. drug use, but suggest that unrecognized co-factors may be important in the development of renal disease.     

Clinical follow-up of 54 patients with IgM-nephropathy

The clinical course of mesangial glomerulopathy with IgM deposits (IgM-nephropathy) was studied in 54 patients. The initial manifestations of the disease were nephrotic syndrome in 18, proteinuria in 21, proteinuria together with hematuria in 4 and isolated hematuria in 11 patients. The nephrotic syndrome was steroid-responsive in 60% of cases and of these 80% were steroid-dependent. During a 5-year postbiopsy follow-up 3 patients went into terminal uremia and in 6 more patients a milder renal insufficiency was observed. Three patients were rebiopsied and in 2 of these the second biopsy specimen disclosed typical focal and segmental glomerulosclerosis. Hematuria was a favorable sign, as no patient with hematuria showed progressive impairment of renal function. The prevalence of hypertension in the whole material was 37%. At close of follow-up 35% of all patients were in clinical remission. It is suggested that IgM-nephropathy associated with abundant proteinuria or the nephrotic syndrome represents a distinct disorder from that associated with hematuria. While the nephrotic type often manifested itself with a morphologic change and a tendency to develop renal insufficiency, the hematuric type showed female predominance, a high tendency to spontaneous clinical remission and a favorable clinical course.     

Nephrotic Range Proteinuria in Renal Transplantation: Clinical and Histologic Correlates in a 10-year Retrospective Study

Introduction

There is a high incidence of nephrotic proteinuria in renal transplant recipients, which is an accurate predictor of graft loss. Despite this, its histologic correlates and prognostic implications are still not well characterized. We assessed the clinical and histological correlates of kidney transplantation patients with nephrotic range proteinuria.

Lipoprotein glomerulopathy associated with psoriasis vulgaris: report of 2 cases with apolipoprotein E3/3

Lipoprotein glomerulopathy (LPG) is a rare disease, characterized by a special histology, including dilated glomerular capillaries filled with pale-stained and meshlike lipoprotein thrombi. It always presents with proteinuria or nephrotic syndrome. Although hyperlipidemia is not always seen, most patients have type III hyperlipoproteinemia with apolipoprotein (apo) E2/3 phenotyping. Although the clinical feature of LPG is rarely described, LPG associated with other glomerulopathy, including IgA nephropathy, membranous nephropathy, and lupus nephritis, has been documented. Until now, there have been no reports of psoriasis vulgaris associated with LPG. The authors present 2 cases of LPG with apo E3/3 genotyping associated with psoriasis vulgaris. The first patient was a 65-year-old woman who presented with nephrotic syndrome with daily urinary protein loss of 9.05 g and itchy erythematous scaly plaques on her trunk and lower limbs for 1 year. The renal biopsy results showed LPG, and the skin biopsy results showed psoriasis. The second patient was a 50-year-old man with history of psoriasis over his trunk and 4 limbs for 30 years. He also presented with nephrotic syndrome with daily urinary protein loss of 7.55 g. The renal biopsy results also showed LPG. The genotype of apo E showed E3/3, and lipoprotein electrophoresis showed a type III hyperlipoproteinemia-like pattern in both cases. The authors suggest that presence of apo E3/3 genotype cannot rule out the diagnosis of type III hyperlipoproteinemia and LPG. Besides, LPG should be included in the differential diagnosis of psoriatic patients with nephrotic syndrome, especially in Asian patients who show poor response to traditional therapy. Renal biopsy should be performed to make the definitive diagnosis.     

A case of necrotizing glomerulonephritis presenting with nephrotic syndrome associated with pulmonary cryptococcosis

We describe a 68-year-old man with necrotizing glomerulonephritis who presented with nephrotic syndrome accompanied by pulmonary cryptococcosis. He developed rheumatoid arthritis in July 1999 and was treated with low-dose prednisolone. He was admitted to our hospital on November 22 following the appearance of bilateral leg edema in October 2000. Laboratory tests at presentation revealed nephrotic syndrome with renal impairment. Renal biopsy specimens revealed necrotizing glomerulonephritis with crescent, but immunofluorescence study showed lack of staining for immunoglobulins or complement components. Chest X-ray and CT showed abnormal shadows in the right upper lung field, and Cryptococcus neoformans was isolated in a transbronchial lung biopsy. After the diagnosis of pulmonary cryptococcosis was made, the patient was treated with 200mg/day fluconazole. The pulmonary abnormal shadows immediately improved and urinary protein excretion dramatically decreased. A second renal biopsy, performed about 2 months after the first biopsy, showed disappearance of crescent. Electron microscopic examination of the second renal biopsy showed partial effacement of foot processes without electron-dense deposits. Our findings suggest that necrotizing glomerulonephritis with nephrotic syndrome in this patient represented pauci-immune T-cell-mediated injury related to pulmonary cryptococcosis.     

Renal lesions in sickle cell nephropathy in children

Sickle cell nephropathy characterized by proteinuria and predominantly glomerular lesions has not been studied as extensively as renal tubular alterations in sickle cell disease. We reviewed our experience with this entity over a 14-year period. Of 13 children with either proteinuria or the nephrotic syndrome, 8 showed focal and segmental glomerulosclerosis, and 5 had mesangial proliferation. Children with focal and segmental glomerulosclerosis were older at onset of nephropathy and presented with the nephrotic syndrome more frequently than those with mesangial proliferation (p less than 0.05). All patients with mesangial proliferation and half of the focal and segmental glomerulosclerosis patients had supranormal renal clearances at onset of nephropathy suggesting hyperfiltration. Hyperfiltration seen in animals with reduced renal mass, and in human diabetic nephropathy before reduction in nephron units leads to mesangial proliferation and sclerosis. Our study suggests that sickle cell disease produces similar lesions in patients with sickle cell nephropathy.