Nephrotic syndrome and aberrant expression of laminin isoforms in glomerular basement membranes for an infant with Herlitz junctional epidermolysis bullosa

Herlitz junctional epidermolysis bullosa (H-JEB) is a hereditary bullous disease caused by absent expression of laminin-5, a component of anchoring filaments within the dermal-epidermal basement membrane zone. Affected individuals usually die during the first 1 year of life. We studied an infant with H-JEB who presented with nephrotic syndrome, a previously unreported complication that may contribute to early death in this disease. DNA analysis revealed a compound heterozygote for mutations 2379delG and Q995X in the LAMB3 gene. The patient had massive albuminuria, attributable to failure of the glomerular filtration barrier, and high urinary N-acetylglucosaminidase levels, indicating renal tubular involvement. Electron-microscopic examination of the renal tissue revealed diffuse fusion of the foot processes, irregular swelling of the lamina rara interna, and disappearance of endothelial cell fenestrations. Immunohistopathologic analysis of the patient's renal tissue revealed compositional changes in laminin isoforms of the glomerular basement membrane and no detectable laminin-5 in the renal tubular basement membrane, which suggests that laminin-5 may play an important role in renal function. Our findings strongly suggest that H-JEB should be considered in the spectrum of congenital nephrotic syndromes. Combination therapy with meticulous skin care and treatment strategies established for congenital nephrotic syndromes may rescue patients with this disease.     

Progression of orthostatic proteinuria to focal and segmental glomerulosclerosis

Focal glomerulosclerosis, with the nephrotic syndrome and progressive renal insufficiency, developed in a 15-year-old boy who presented initially 1 year earlier with orthostatic proteinuria. Although generally considered to be a benign disorder, this case suggests that on rare occasions, serious glomerular diseases may develop in patients with orthostatic proteinuria or that significant glomerular disease may occasionally present with postural proteinuria.     

Membranous nephropathy presenting with nephrotic syndrome in a child with thalassemia major

Few data on the renal effects of thalassemia syndrome are available in the literature. Recent clinical studies identified proximal tubular damage and glomerular filtration abnormalities in thalassemia. Iron‐chelating agents might be nephrotoxic as well, but proven glomerular injury, either due to anemia or chelating therapy, has not previously been demonstrated in thalassemia patients. Here, we report the first thalassemia patient presenting with nephrotic syndrome to be diagnosed with membranous nephropathy in the literature.     

Nephrotic syndrome and B leukemia

A boy, aged 14 1/2 years, presented with Burkitt leukemia. His renal status was normal before treatment. Chemotherapy (SFOP LMB 86 protocol) was begun Oct. 9, 1986. After the first 2 courses of chemotherapy, the patient had Gram negative sepsis treated with cefotaxime, netilmycine, Vancomycin and ornidazole. During sepsis, nephrotic syndrome developed (albumin 25 g/l, non selective proteinuria 15 g/24 h), with moderately high blood pressure, functional renal failure (creatinine 141 mumols/l, U/P urea = 20), polyuria and tubular damage. Kidney ultrasonography was normal. Needle biopsy showed minimal glomerular lesions, acute tubular lesions, and no deposits in immunofluorescence. The nephrotic syndrome disappeared within 3 weeks, with treatment of leukemia. He is at present in complete remission with a follow-up of 25 months.     

A familial syndrome of growth retardation, severe Fanconi-type renal disease and glomerular changes--a new entity?

Two young siblings had a syndrome of growth retardation, severe rickets, anemia, renal insufficiency, and renal tubular dysfunction, the last including acidosis, aminoaciduria, and polyuria. There was moderate psychomotor developmental delay. Neither child had cystinosis. Renal biopsy in the older child revealed severe glomerular abnormalities, with capillary wall thickening reminiscent of the hemolytic-uremic syndrome. The proximal convoluted tubules were lined with short, cuboidal cells containing mildly abnormal mitochondria. There was also thinning of brush border microvilli and basolateral infoldings, perhaps as the result of regressive changes, and interstitial fibrous tissue was moderately increased. The etiology of the tubular and glomerular changes is uncertain. We believe these patients represent a previously unreported hereditary syndrome sharing certain clinical features with severe nephropathic cystinosis.     

Mécanismes moléculaires du syndrome néphrotique idiopathiqueMolecular basis of idiopathic nephrotic syndrome.

Steroid-sensitive idiopathic nephrotic syndrome is a T-cell disorder associated with a functional renal impairment. The molecular mechanisms leading from the stimulation of the immune system to the clinical expression of the renal disease can be analyzed according to five biological events: 1) a Th2 activation of T-cells by interleukin-13; 2) a yet unidentified glomerular permeability factor from immune origin; 3) a molecular disorientation of slit diaphragms or glomerular basement membrane responsible for proteinuria; 4) a podocyte cytoskeleton rearrangement responsible for foot process effacement; and 5) renal avidity for sodium and edema formation resulting from a primary stimulation of tubular Na,K-ATPase and an increase of endothelial permeability.     

The Significance of Focal Global Sclerosis in Idiopathic Nephrotic Syndrome

ABSTRACT. The clinical course of five pediatric patients with idiopathic nephrotic syndrome associated with focal global sclerosis in renal biopsy was analyzed retrospectively. The condition was defined as complete obsolescence of more than 15 % of glomeruli associated with tubular atrophy and interstitial fibrosis. At onset, all children had a steriod-sensitive relapsing nephrotic syndrome. Two became steroid-dependent and one steroid-resistent. Cyclophosphamide or chlorambucil treatment was initially followed by remission in all patients; a second course was successful in one of two patients. After 12 to 18 years of observation, four patients are in remission for periods of 2 to 12 years. Glomerular filtration rate is slightly reduced in only one patient. This study suggests that the clinical course of children with idiopathic nephrotic syndrome associated with focal global sclerosis is similar to that observed in patients with minimal glomerular changes but different from that in patients with focal segmental sclerosis.     

Mécanismes moléculaires du syndrome néphrotique idiopathique

Steroid-sensitive idiopathic nephrotic syndrome is a T-cell disorder associated with a functional renal impairment. The molecular mechanisms leading from the stimulation of the immune system to the clinical expression of the renal disease can be analyzed according to five biological events: 1) a Th2 activation of T-cells by interleukin-13; 2) a yet unidentified glomerular permeability factor from immune origin; 3) a molecular disorientation of slit diaphragms or glomerular basement membrane responsible for proteinuria; 4) a podocyte cytoskeleton rearrangement responsible for foot process effacement; and 5) renal avidity for sodium and edema formation resulting from a primary stimulation of tubular Na,K-ATPase and an increase of endothelial permeability.     

Serum and urinary neutrophil gelatinase‐associated lipocalin levels in children with chronic renal diseases

Background: Recent studies showed that serum and urinary neutrophil gelatinase‐associated lipocalin (NGAL) represents a novel, sensitive, specific biomarker for early detection of acute kidney injury. However, the clinical significance of measuring serum and urinary NGAL on chronic renal diseases remains unclear. Methods: In this study, we measured serum and urinary NGAL levels in patients with several common pediatric renal diseases such as renal dysfunction (estimated glomerular filtration rate < 90 mL/min/1.73 m²), proliferative glomerulonephritis, steroid‐resistant and steroid‐sensitive nephrotic syndrome, and tubular dysfunction. Results: Urinary NGAL level was significantly increased compared with the control in all of these disease groups except in patients with a remission stage of steroid‐sensitive nephrotic syndrome, although a significant increase in serum NGAL level was observed in the renal dysfunction group only. Both serum and urinary NGAL levels showed significant inverse correlations with an estimated glomerular filtration rate in the analysis with total subjects, and also in the analysis with the renal dysfunction group in urinary NGAL. In proteinuric patients, the extent of proteinuria significantly correlated with urinary NGAL level. In patients with tubular dysfunction, the increase of urinary NGAL level was remarkable compared with the other disease groups. Conclusion: These results indicated that urinary NGAL level is a better biomarker for chronic renal diseases in children than serum NGAL level, although multiple pathological mechanisms should be considered in evaluating these NGAL values.     

The significance of focal global sclerosis in idiopathic nephrotic syndrome. Long-term clinical observations

The clinical course of five pediatric patients with idiopathic nephrotic syndrome associated with focal global sclerosis in renal biopsy was analyzed retrospectively. The condition was defined as complete obsolescence of more than 15% of glomeruli associated with tubular atrophy and interstitial fibrosis. At onset, all children had a steroid-sensitive relapsing nephrotic syndrome. Two became steroid-dependent and one steroid-resistant. Cyclophosphamide or chlorambucil treatment was initially followed by remission in all patients; a second course was successful in one of two patients. After 12 to 18 years of observation, four patients are in remission for periods of 2 to 12 years. Glomerular filtration rate is slightly reduced in only one patient. This study suggests that the clinical course of children with idiopathic nephrotic syndrome associated with focal global sclerosis is similar to that observed in patients with minimal glomerular changes but different from that in patients with focal segmental sclerosis.     

Left atrial atheromatosis in childhood nephrotic syndrome

Three male children who had onset, at approximately age 2 years, of nephrotic syndrome, which progressed to renal insufficiency had left atrial atheromatosis at autopsy disproportionate to the degree of aortic or vascular atheromatosis found. The atrial atheromatous process was distributed in elongated nodules, which had a ridged or corduroy-like appearance on gross examination. Two of the patients showed renal lesions of advanced focal glomerulosclerosis, but one had membranoproliferative glomerulopathy, suggesting that the "syndrome" of early onset nephrotic syndrome progressing to renal insufficiency, hyperlipidemia, and exaggerated left atrial atheromatosis, of which association we have not found a specific report, is etiologically heterogeneous. The patients reported died in 1943, 1952, and 1963. Whether more recent methods of treatment of nephrotic syndrome, hyperlipidemia, or chronic renal insufficiency in children have altered the incidence of such disproportionate left atrial atheromatosis is not known.     

The pediatric nephrotic syndrome spectrum: clinical homogeneity and molecular heterogeneity

Idiopathic nephrotic syndrome is the most common glomerular disorder of childhood. Recurrence of nephrotic syndrome immediately following renal transplantation is rapid, results in a high rate of graft loss, and represents the most severe form of nephrotic syndrome. This review discusses the molecular heterogeneity of pediatric nephrotic syndrome across the spectrum of disease activity. A schema is offered for a molecular approach to pediatric nephrotic syndrome, including immune-mediated and structural/genetic factors.     

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??Objective??To explore and conclude the pathological categories and clinical data of childhood renal diseases and understand the importance of renal biopsy in childhood renal diseases. Methods??Totally 753 patients who underwent percutaneous renal biopsy from 1995 to 2015 were selected as study subjects??and their clinical and pathological information was analyzed retrospectively. Results??Among 753 patients who underwent percutaneous renal biopsy??428 cases??56.84%?? had primary glomerular disease??306 cases??40.64%?? had secondary glomerular disease??17 cases??2.26%?? had heritage glomerular disease??and 2 cases??0.27%?? had renal tubular interstitial disease. The most common clinical diagnosis were primary nephritic syndrome. The most common clinical diagnosis and pathological category in primary glomerulary disease were primary nephritic syndrome and IgA nephropathy respectively?? and in secondary glomerulary disease they were purpura nephritis and mesangial proliferative glomerulonephritis respectively. Thin basement membrane disease and Alport’s syndrome are the most common pathological category of the heritage glomerular disease. The 8 repeated renal biopsies showed pathological and clinical progression. Conclusion??The primary glomerulary disease is the main type of childhood glomerulary diseases??The most common clinical diagnosis and pathological category are primary nephrotic syndrome and mesangial proliferative glomerulonephritis respectively. The repeated renal biopsy is beneficial to control the transformation of pathological types and adjust new treatments timely.     

Renal effects of cyclosporin A in children treated for idiopathic nephrotic syndrome

Little data have been published on tubular renal function during cyclosporin A treatment in children without transplants. We studied 12 young subjects (mean age 10 years) with steroid-responsive idiopathic nephrotic syndrome and with signs of steroid toxicity. After achieving remission with prednisone 60 mg/m², 8 children started cyclosporin A therapy (6 mg/kg/day) (group A) and 4 children were given cyclophosphamide 2.5 mg/kg/day (group B). The latter were considered as controls together with 10 other children with idiopathic nephrotic syndrome in complete remission and off therapy (group C). We monitored creatinine clearance and tubular handling of β₂-microglobulin, sodium, phosphorus and uric acid for one year. Cyclosporin A induced a decrease in creatinine clearance with a decrease in fractional excretion of β₂-microglobulin; sodium excretion was similar in the two treated groups and a transient decrease in fractional excretion of uric acid was seen only in patients receiving cyclosporin A. Both groups showed an increased renal threshold phosphate concentration. Our results suggest that in children, cyclosporin A therapy induces a decrease in glomerular filtration rate associated with increased reabsorption activity of proximal tubular cells.     

Left Atrial Atheromatosis in Childhood Nephrotic Syndrome

Three male children who had onset, at approximately age 2 years, of nephrotic syndrome, which progressed to renal insufficiency had left atrial atheromatosis at autopsy disproportionate to the degree of aortic or vascular atheromatosis found. The atrial atheromatous process was distributed in elongated nodules, which had a ridged or corduroy-like appearance on gross examination. Two of the patients showed renal lesions of advanced focal glomerulosclerosis, but one had membranoproliferative glomenilopathy, suggesting that the “syndrome” of early onset nephrotic syndrome” progressing to renal insufficiency, hyperlipidemia, and exaggerated left atrial atheromatosis, of which association we have not found a specific report, is etiologically heterogeneous. The patients reported died in 1943, 1952, and 1963. Whether more recent methods of treatment of nephrotic syndrome, hyperlipidemia, or chronic renal insufficiency in children have altered the incidence of such disproportionate left atrial atheromatosis is not known.     

Clinicopathologic correlations in the nephrotic syndrome.

The wide utilization of renal biopsy and the introduction of electron microscopic and immunohistologic methods has allowed better definition of the clinico-pathological conditions associated with the nephrotic syndrome (NS). Two major categories of facts can be differentiated. In the first one, diffuse lesions of glomeruli, either secondary to specific diseases, or apparently primary diseases such as membranous or membrano-proliferative glomerulonephropathy (GN) are responsible for the increased permeability of the glomerular capillaries. In most of these, there is evidence that immunological mechanisms play a role in the injury of the glomerular capillary. Any of the following clinical symptoms are suggestive of this category of NS: an acute nephritic onset, a moderate NS, macroscopic hematuria, marked hypertension and/or renal insufficiency, poorly selective proteinuria and decreased plasma C3 levels. Patients affected with any of these glomerulopathies usually do not respond to steroids. In the second one, usually referred to as the idiopathic nephrotic syndrome (INS) the mechanism of glomerular capillary alteration is unknown and the nephrotic syndrome is more marked. Minimal change NS (MCNS) accounts for the great majority of INS and is characterized in most cases by a selective proteinuria, the absence of hematuria, a good response to steroids and a good prognosis. However, in some instances, renal biopsy reveals either diffuse mesangial proliferation (DMP) or focal glomerular sclerosis (which may be superimposed on MCNS or on DMP). In both instances, hematuria may be present and 50--75% of patients do not respond to steroids and have a poor prognosis. There is still considerable controversy about the exact relationship between these 3 patterns. We believe that they are not distinct entities but represent variants of the same disease. In addition to these 2 major categories of NS, there are, in infancy, 2 conditions associated with a NS of poor prognosis: congenital NS of Finnish type and infantile mesangial sclerosis. Since steroid-sensitive nephrosis is by far the commonest cause of NS especially in young children up to 8 years, a renal biopsy should be performed only in 2 instances: (a) when the clinical symptoms suggest diffuse glomerular lesions, and (b) when steroid resistance has been demonstrated.     

Nephrotic Range Protienuria as a Presenting Feature of Classical Nephropathic Cystinosis

Patients with renal tubular acidosis (RTA) usually have tubular or low molecular weight proteinuria. The authors present a rare case of a 6-y-old girl with Fanconi syndrome secondary to cystinosis, who at presentation had nephrotic range proteinuria along with rickets and failure to thrive. Although hypoalbuminemia and massive proteinuria are characteristics of nephrotic syndrome, there are other conditions which can present with massive proteinuria.     

1 316例小儿肾脏病临床与病理分布特点

目的：了解小儿肾小球疾病肾脏病理改变的特点及其与临床表现的关系。方法：对近20年间该院的1 316例患儿的肾活检资料,进行了回顾性分析。结果：1 316例患儿中临床主要表现为肾病综合征(383例,占29.09% )、急性肾炎综合征(291例,占22.00%)、孤立性血尿(224例,占17.21%)、紫癜性肾炎（209例,占15.87%）、乙型肝炎病毒相关肾炎(96例,占7.30% )等。病理改变主要为系膜增生(756例,占57.45%)、IgA肾病(113例,占8.59% )、毛细血管内增生（112例,占8.51%）、膜性肾病(66例,占5.02%)、微小和轻微病变(59例,占4.48%)等。通过超微结构检查,使Alport综合征、薄基底膜病、先天性肾病、纤维样肾小球病、Fabry病等,得以明确诊断。通过肾活检组织免疫病理学检查,使IgA肾病、IgM肾病及C1q肾病得以确诊。肾活检患儿中原发性肾小球疾病最为常见（915例,占69.53%）。原发性肾小球疾病病因以原发性肾病综合征为最常见（375/915例,占41.0%）,而继发性肾小球疾病病因以紫癜性肾炎为最常见（209/344例,占60.8%）。结论： 在该次调查的肾活检资料中,原发性肾小球疾病最常见,肾病综合征是最常见的临床诊断,病理改变则以系膜增生最为多见。［中国当代儿科杂志,2007,9（2）：117-121］     

Pierson syndrome: a novel cause of congenital nephrotic syndrome

In this report, we describe a newborn infant who presented with congenital nephrotic syndrome and renal insufficiency, as well as bilateral microcoria. This constellation of findings is a hallmark of Pierson syndrome, a newly recognized genetic disorder that is caused by a deficiency of beta2 laminin in the basement membrane. Our patient demonstrated classic histopathologic findings of Pierson syndrome on renal biopsy, including absence of beta2 laminin on immunofluorescent staining, and genetic testing confirmed the diagnosis. We conclude that Pierson syndrome should be included in the differential diagnosis for congenital nephrotic syndrome, especially in patients with ocular abnormalities.