儿童过敏性紫癜性肾炎与IgA肾病的临床和病理的对比研究

目的　对比研究过敏性紫癜性肾炎 (HSPN)和IgA肾病在临床、实验室检查及肾脏病理改变上的异同 ,探讨两者的关系。方法　对经肾活检证实的 31例IgA肾病及 12 0例过敏性紫癜性肾炎患儿进行详细的临床及病理对比分析。结果　 2 5 8%的IgA肾病发病年龄在 12岁以上 ,而HSPN中仅占 10 .0 % ,差异有显著意义 (P <0 0 5 )。二组患儿临床表现类型分布上相似 ,但HSPN肾外症状多 ,均有皮肤紫癜 ,5 9 2 %有胃肠症状 ,4 6 7%有关节痛 ,而IgA肾病仅 3 2 %有腹痛。在肾脏病理改变上 ,IgA肾病 35 5 %出现球性硬化、4 1 9%系膜硬化 ,HSPN分别为 3 1%及 6 3% ,但HSPN有 6 5 6 %出现内皮增生 ,IgA肾病仅 2 9 0 % ,差异均有非常显著意义 (P <0 0 1)。IgA肾病中 6 5 %合并有薄基底膜病变 ,HSPN未见薄基底膜病变。电镜下HSPN电子致密物稀疏、松散 ,沉积部位分布较为广泛 ,位于肾小球系膜、内皮下甚至基底膜内 ,而IgA肾病电子致密物成密集团块状 ,主要局限于系膜区及旁系膜区。HSPN患儿中 2 3例 (71 9% )肾小球免疫沉积物中含有IgG ,其中 6例以IgG为主 (4例 )或毛细血管壁有IgG线样沉积 (2例 ) ,而IgA肾病肾小球免疫沉积物中有IgG沉积的仅为 19 4 % ,其多为IgA伴IgM和 (或 )C3 沉积 ,未见以IgG沉积为主以及线样IgG沉积     

川崎病合并IgA肾病1例报告并文献复习

目的 报告1例儿童川崎病合并IgA肾病并文献复习,以提高对该病的认识和临床诊疗水平.方法 根据患儿的症状、体征及心脏超声检查结果进行诊断,并结合文献资料进行分析.结果 男孩,7岁,皮疹、发热后3周出现蛋白尿、镜下血尿.超声心动图(UCG)检查发现左右冠状动脉改变,肾穿刺病理报告系膜增生性IsA肾病.结论 儿童川崎病合并IgA肾病比较少见,应提高认识,并进行更深入的研究.     

不典型急性链球菌感染后肾小球肾炎3例报告

目的提高对急性肾小球肾炎特殊临床和肾脏病理的认识。方法回顾性分析3例具有不典型急性肾小球肾炎临床表现患儿的临床和病理资料。结果 3例患儿均以急性肾小球肾炎表现起病,例1和例3在病程中出现肾病综合征表现;例2在6周后肉眼血尿方转为镜下血尿;例1于病程11周时仍为肾病水平蛋白尿、直至病程30周时尿蛋白消失;例2和例3分别于病程5周和4周恢复肾功能。例2和例3血清补体C3于病程6周内恢复,例1于病程11周恢复。例2和例3抗链球菌溶血素O(ASO)滴度增高。3例患儿的肾活检组织光镜和电镜改变均符合毛细血管内增生性肾小球肾炎的特点,免疫病理改变例1以IgM和C3沉积为主,例2和例3以C3沉积为主。结论上述3例患儿均诊断为急性链球菌感染后肾小球肾炎,但临床和病理特点具有不典型性。     

Renal functional changes in acute glomerulonephritis in children. A one-year follow-up.

Renal function was studied in three patients with post-streptococcal, four patients with IgA and one patient with non-streptococcal proliferative glomerulonephritis (GN) at the onset of the disease and two, six and 12 months later. Renal biopsies were performed at the onset of the disease and 12 months later. Standard clearance techniques were used for the functional studies. The latter were performed during hydropenia and continuous isotonic saline infusion. During hydropenia, the GFR was uniformly depressed shortly after the onset of the disease, but it normalized during the following two months. The filtration fraction was depressed in poststreptococcal GN at the onset and it normalized with the GFR. In IgA GN, the filtration fraction remained within normal limits during the entire course of the illness. The natriuretic response to isotonic saline volume expansion was low in all patients at the onset of the disease, but normalized in post-streptococcal and IgA GN during the one-year follow-up. In spite of normalized renal function, biopsy findings in IgA GN were unchanged 12 months later. An episode of macroscopic hematuria in one patient with IgA GN at the six-month investigation had no apparent effect on renal function.     

RENAL FUNCTIONAL CHANGES IN ACUTE GLOMERULONEPHRITIS IN CHILDREN. A ONE-YEAR FOLLOW-UP

Abstract. Renal function was studied in three patients with post-streptococcal, four patients with IgA and one patient with non-streptococcal proliferative glomerulonephritis (GN) at the onset of the disease and two, six and 12 months later. Renal biopsies were performed at the onset of the disease and 12 months later. Standard clearance techniques were used for the functional studies. The latter were performed during hydropenia and continuous isotonic saline infusion. During hydropenia, the GFR was uniformly depressed shortly after the onset of the disease, but it normalized during the following two months. The filtration fraction was depressed in poststreptococcal GN at the onset and it normalized with the GFR. In IgA GN, the filtration fraction remained within normal limits during the entire course of the illness. The natriuretic response to isotonic saline volume expansion was low in all patients at the onset of the disease, but normalized in post-streptococcal and IgA GN during the one-year follow-up. In spite of normalized renal function, biopsy findings in IgA GN were unchanged 12 months later. An episode of macroscopic hematuria in one patient with IgA GN at the six-month investigation had no apparent effect on renal function.     

Pathological improvement of IgA nephropathy and Henoch-Schönlein purpura nephritis with urokinase therapy

The pathological findings of 13 patients with immunoglobulin A (IgA) nephropathy or Henoch-Schönlein purpura nephritis before and after urokinase (UK) administration were investigated retrospectively. The mean activity index value decreased significantly at the time of the second biopsy compared with that of the biopsy before UK treatment. The mean chronicity index value, which was considered to reflect the renal outcome, before and after UK treatment did not change significantly, although it improved significantly in six patients. Immunofluorescence microscopy showed that the immune deposition of C3 decreased, but that of IgA and fibrin-related antigen were unchanged, by UK therapy. These results suggest that UK may prevent the mesangial proliferation associated with IgA nephropathy and Henoch-Schönlein purpura nephritis not only by its fibrinolytic action, but also by other mechanisms, such as digestion of the mesangial matrices.     

Reflux nephropathy complicated by acute post-streptococcal glomerulonephritis

A 7 years old male with severe bilateral vesicoureteral reflux developed acute renal failure without evidence of either infection or obstruction. The diagnosis of acute post-streptococcal glomerulonephritis was confirmed by clinical, serological and histological evaluation. The patient's creatinine clearance decreased from 25 ml/min/1.73 m2 to 10-13 ml/min/1.73 m2 following the acute nephritic episode and chronic dialysis therapy was required thereafter. This patient illustrates that a glomerular etiology should be suspected when acute renal failure occurs in a patient with reflux nephropathy and suggests that the prognosis of acute post-streptococcal glomerulonephritis may be worse in children with pre-existing renal disease.     

Focal segmental glomerular sclerosis in three generations of a single family

We studied members of three generations of a family presenting a nephropathy characterized by proteinuria, occasional microscopic hematuria, progressive deterioration of renal function and an autosomic dominant hereditary pattern. In seven percutaneous needle biopsies, examination by light microscopy showed findings compatible with Focal Segmental Glomerulosclerosis (FSGS) in six patients and Focal Global Glomerulosclerosis (FGG) in one case. Deposits of immunoglobulins IgM, IgA and C3 following mesangial and peripheral distribution were observed. According to electron microscopy, the basal membrane was unchanged though electron dense deposits were found at subendothelial, subepithelial and mesangial locations.     

儿童急性感染后IgA为主型肾小球肾炎1例报道并文献复习

目的 提高对儿童急性感染后IgA为主型肾小球肾炎（简称肾炎）临床和病理特征的认识。方法分析1例急性感染后IgA为主型肾炎患儿的临床和病理资料,并结合文献分析其临床特点、诊断、发病机制、治疗及预后。结果 本例患儿临床表现为肉眼血尿、大量蛋白尿、急性肾损伤,抗链球菌溶血素“0”(ASO)升高、血清IgA升高等,肾脏病理组织学见肾小球系膜细胞轻度增生性病变,免疫荧光见IgA（+） 、C3（+）沉积于肾小球系膜区和血管襻;电镜见肾小球上皮下“驼峰”样电子致密物沉积伴系膜区少量致密物沉积。在病程9周时患儿肾功能恢复正常,血尿和蛋白尿消失。结论急性感染后IgA为主型肾炎临床和病理特征均具有不典型性,诊断依赖早期肾活检,电镜检查必不可少,短期疗效尚可,远期疗效仍需观察。     

儿童IgA血管炎肾损伤与IgA肾病

关于IgA血管炎肾损伤的认识较IgA肾病早约160年。前者通常依据临床表现便可诊断,后者确诊则依赖肾活检。虽然近年研究显示二者在发病机制、临床表现、病理、治疗方面具有相同之处,然而在预后、发病年龄方面却存在不同,且IgA血管炎并非一定出现肾脏受累的临床表现、IgA肾病无皮肤受累表现,表明需要鉴别IgA血管炎肾损伤和IgA肾病。已有研究不足以证实IgA血管炎肾损伤和IgA肾病是同一疾病的不同临床表现的假说。     

合并使用咪唑立宾及贝那普利诱发高尿酸血症伴急性肾损伤1例报告并文献复习

目的 探讨咪唑立宾(MZR)诱发高尿酸血症及急性肾损伤(AKI)的临床特点及发病机制.方法 回顾分析1例合并使用MZR及贝那普利诱发高尿酸血症伴AKI的IgA肾病患儿的临床资料.结果 男性患儿,13岁,确诊IgA肾病5个月,基础肾功能无异常,合并使用MZR和贝那普利后出现一过性高尿酸血症和AKI,尿酸清除率明显降低至3...     

Alteration of lung diffusion capacity in IgA nephropathy.

OBJECTIVE: To establish whether changes of lung transfer for carbon monoxide (TLCO) are related to the phase of IgA nephropathy. METHODS: Respiratory function was tested in 12 children with IgA nephropathy assessed by percutaneous renal biopsy. This was done during acute exacerbations or haematuria-free phases of the disease. RESULTS: TLCO was low in 12/13 measurements made in the haematuric phase of IgA nephropathy or during the month following gross haematuria (mean TLCO 64% of expected values). Lung volumes and blood gas values were normal and only minor radiological signs of interstial lung involvement were observed in 11/12 patients. When respiratory tests were performed more than three months after gross haematuria, TLCO was low in 4/9 patients, with no relation to the significance of residual proteinuria or severity of findings at renal biopsy. There was a significant difference between tests performed when haematuria was present or recent and those performed more than three months after an episode of gross haematuria (p < 0.01). CONCLUSIONS: The decrease of TLCO in the acute phases of the disease is probably related to alterations of the lung alveolarcapillary membrane by immune complexes containing IgA. This non-invasive technique, easy to perform and repeat, could be of value in the diagnosis of IgA nephropathy in haematuric children.     

Alteration of lung diffusion capacity in IgA nephropathy

OBJECTIVE: To establish whether changes of lung transfer for carbon monoxide (TLCO) are related to the phase of IgA nephropathy. METHODS: Respiratory function was tested in 12 children with IgA nephropathy assessed by percutaneous renal biopsy. This was done during acute exacerbations or haematuria-free phases of the disease. RESULTS: TLCO was low in 12/13 measurements made in the haematuric phase of IgA nephropathy or during the month following gross haematuria (mean TLCO 64% of expected values). Lung volumes and blood gas values were normal and only minor radiological signs of interstial lung involvement were observed in 11/12 patients. When respiratory tests were performed more than three months after gross haematuria, TLCO was low in 4/9 patients, with no relation to the significance of residual proteinuria or severity of findings at renal biopsy. There was a significant difference between tests performed when haematuria was present or recent and those performed more than three months after an episode of gross haematuria (p < 0.01). CONCLUSIONS: The decrease of TLCO in the acute phases of the disease is probably related to alterations of the lung alveolarcapillary membrane by immune complexes containing IgA. This non-invasive technique, easy to perform and repeat, could be of value in the diagnosis of IgA nephropathy in haematuric children.     

IgA nephropathy associated with a novel N-terminal mutation in factor H

Most patients with IgA nephropathy exhibit complement deposition in the glomerular mesangium. Certain cases of IgA nephropathy have been associated with reduced levels of complement factor H. A recent study could not demonstrate mutations at the C-terminal of factor H. We describe a novel heterozygous mutation in factor H, position A48S (nucleotide position 142 G > T, alanine > serine), detected in exon 2 of a 14-year-old girl with IgA nephropathy. The patient exhibited reduced levels of C3 and factor H, the latter suggesting that the mutation affected factor H secretion. The patient developed initial signs and symptoms of glomerulonephritis at the age of 9 years but presented again at the age of 14 years with weight gain, renal failure, nephrotic-range proteinuria and malignant hypertension. Blood tests suggested the development of microangiopathic hemolytic anemia (MAHA) but the renal biopsy was mostly indicative of chronic changes associated with IgA nephropathy as well as vascular changes associated with malignant hypertension. Immunofluorescence exhibited deposits of IgA, C3, and IgM. Screening of the factor H gene revealed, in addition to the mutation, three heterozygous hemolytic uremic syndrome -associated risk polymorphisms (−257 c/t, 2089 a/g, and 2881 g/t) which may have increased the patient’s susceptibility to the occurrence of MAHA triggered by malignant hypertension. The combined clinical picture of IgA nephropathy and MAHA may have been partly related to the alterations in factor H.     

Unusual radiographic presentation of IgA nephropathy

An adolescent male presented with hematuria and flank pain. Transient focal renal parenchymal defects were demonstrated by ultrasonography, radionuclide scintigraphy and computed tomography. Renal biopsy revealed IgA nephropathy with acute tubular necrosis. This peculiar radiographic pattern has not, to our knowledge, been previously described in IgA nephropathy and may relate to tubule cell damage by red blood cell casts or patchy renal ischemia.     

儿童IgA肾病72例临床与病理分析

目的探讨儿童IgA肾病(IgAN)的临床、病理特点及其相关关系。方法对本院2005年5月-2011年8月经肾穿刺活检确诊为IgAN的72例患儿的临床表现、临床分型、病理特点及免疫分型进行回顾性总结,并分析它们之间的相关关系。结果本组72例。男48例,女24例;年龄1岁5个月～17岁[(8.99±2.94)岁];入院时病程2 d～9 a(平均12.86个月)。临床以血尿起病者58例(包括38例肉眼血尿及5例伴水肿者),以单纯水肿起病者12例,以蛋白尿起病者2例。临床分型为肾病综合征型28例(38.89%)、孤立性血尿型19例(26.39%)、血尿和蛋白尿型13例(18.05%)、急性肾炎型10例(13.89%)、孤立性蛋白尿型2例(2.78%)。病理改变:系膜增生型肾小球肾炎40例,局灶增生型肾炎25例、毛细血管内增生型肾炎6例、新月体型肾炎1例。其中伴新月体形成者17例(占23.61%)。免疫组织化学可见多种免疫球蛋白沉积。沉积类型为满堂亮型1例、IgA+IgG+C32例、IgA型8例、IgA+IgM+IgG+C3型17例、IgA+IgM+C3型44例。结论 IgAN的临床表现形式多样,其病情轻重与起病形式无关。病理表现以系膜增生型肾小球肾炎为主,免疫球蛋白沉积以复合型为主。临床表现为肾病综合征型及血尿和蛋白尿型者病理较重,应尽早行肾穿,及时治疗。     

Glomerular Membranopathy in Children with IgA Nephropathy and Henoch Schönlein Purpura

We evaluated renal biopsies from 34 children with IgA nephropathy or Henoch Schönlein purpura to further characterize the ultrastructural features of the glomerular membranopathy that occurs in these disorders. Focal glomerular basement membrane damage was identified in 29 children and was severe in 4 of the children. Alterations included focal and segmental attenuation, splitting, duplications, and spike-like subepithelial protrusions of the lamina densa, along with saccular glomerular microaneurysms arising at the paramesangium. Those cases with extensive glomerular basement membrane lesions had either moderate or severe glomerular alterations apparent by light microscopy. Over half of the cases with glomerular membranopathy had immunohistological or ultrastructural evidence of focal peripheral glomerular capillary wall immune deposits and electron-dense deposits occurred at sites of glomerular basement membrane splitting. Despite the focal attenuation of the glomerular basement membrane, we did not identify any biopsy with findings of thin basement membrane disease. The glomerular basement membrane ultrastructural findings we describe are characteristic of IgA nephropathy and Henoch Schönlein purpura, are common in children with these disorders, and are similar to the ultrastructural alterations of the basement membrane that occur in other glomerulonephritides. These basement membrane injuries may be inflammatory cell or immune mediated but their pathogenesis requires further study.     

T cell subsets in glomerulonephritis

Abnormal lymphocyte function has been postulated to have a pathogenetic role in nephrotic syndrome. In an attempt to investigate the pathogenetic role of lymphocyte subsets in human glomerular disease, we studied 110 children suffering from nephritis during the acute nephrotic phase or nephritis without steroid treatment, 4 weeks later after steroid treatment, in remission and relapse. These patients included minimal change nephrotic syndrome (MCNS) 15 cases, focal segmental glomerular sclerosis (FGS) 6 cases, mesangial cell proliferative nephropathy (MesPGN) 42 cases, membranoproliferative glomerulonephritis (MPGN) 2 cases, hepatitis B surface antigenemia associated with membranous nephropathy (HBVMN) 10 cases, IgA mesangial nephropathy (IgAN) without nephrotic syndrome 7 cases, poststreptococcal glomerulonephritis (PSGN) 24 cases and chronic glomerulonephritis (CGN) 4 cases. There was no significant difference in the total lymphocyte count of each different pathological group of nephritis except that lymphopenia was noted in the CGN patients. When the lymphocyte phenotypic profile was examined, OKT8 cells were significantly increased in the MesPGN patients and both OKT4 and OKT8 cells were significantly increased in HBVMN. Comparison of MCNS and MesPGN during the acute nephrotic phase showed the OKT4/OKT8 ratio decreased significantly in MesPGN. Four weeks after steroid treatment, OKT4 cells decreased both in MCNS and MesPGN being pronounced in MCNS. In the remission stage with steroid treatment the OKT4/OKT8 ratio decreased in MCNS and was mildly elevated in MesPGN. In relapse, the OKT4/OKT8 ratio was the same as it was during the onset of nephrotic phase. MCNS cases were steroid responsive whereas in MesPGN there were frequent relapses or partial steroid response.(ABSTRACT TRUNCATED AT 250 WORDS)     

儿童IgA血管炎肾损伤临床病理特点与预后

IgA血管炎是儿童最常见血管炎,长期预后决定于肾损伤程度,IgA血管炎肾损伤多见于10岁以上男性,血管炎反复(皮疹、腹痛、关节症状)的患儿,97%肾损伤在皮疹后6个月内出现。临床表现多以血尿和蛋白尿为主。肾脏病理是IgA沉积为主的系膜增生为主要病变的肾小球病,临床表现为肾病综合征或早期存在急性肾损伤患儿进展至终末期肾衰竭(ESRD)风险更高,即使表现为轻微血尿和蛋白尿也可能进展至CKD。病理Ⅳ和Ⅴ级更易进展至ESRD,早期逆转肾病状态对长期预后有益。     

Long-term follow up of renal function in IgA nephropathy.

Fifty one children with IgA nephropathy verified at biopsy have been followed up clinically and functionally for 0.4-16.8 years from the onset of symptoms. Renal function was evaluated by determining the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) from the clearances of inulin and para-aminohippuric acid. Fifteen (29%) of the children had raised serum creatinine concentrations at the onset. Mean GFR was significantly lower than that of controls at the first investigation. During the follow up GFR and ERPF decreased and were significantly lower than in the controls after eight years of disease. The significant fall in renal function was found in children with proteinuria and especially in boys, in whom GFR and ERPF decreased from a mean (SEM) of 117 (5) and 616 (31) at 2.8 years to 97 (6) and 509 (36) ml/min/1.73 m2 at 7.5 years. Patients with raised serum creatinine concentrations at the onset had significantly lower GFRs, and patients with macroscopic haematuria at this time did not show decreased renal function at follow up. In conclusion, children with IgA nephropathy do not seem to have a benign clinical course. Boys with proteinuria show a significant decrease in renal function during follow up.