Tubulointerstitial mast cell infiltration in glomerulonephritis

Mast cells are involved in chronic inflammation and tissue fibrosis. To determine whether these cells are also involved in tubulointerstitial injury in glomerulonephritis, we assayed mast cell infiltration in the kidneys of 107 patients with primary or secondary glomerulonephritis. Using a monoclonal antihuman tryptase antibody, we detected mast cells in the renal cortical tubulointerstitium, the periglomerular areas, and the medullary interstitium, but not in glomeruli. Renal cortical tubulointerstitial mast cells, including periglomerular area, were estimated as 0.8+/-1.6 cells/mm2 in minimal change nephrotic syndrome (n=7), 1.5+/-0.7 cells/mm2 in minor glomerular abnormalities without nephrotic syndrome (n=7), 6.5+/-7.7 cells/mm2 in membranous nephropathy(n=10), 12.9+/-15.5 cells/mm2 in lupus nephritis (n=15), 13.4+/-8.3 cells/mm2 in focal segmental glomerular sclerosis (n=6), 18.5+/-21.1 cells/mm2 in ANCA-related nephropathy (n=5), 19.8+/-14.2 cells/mm2 in membranoproliferative glomerulonephritis (n=5), 21.3+/-17.7 cells/mm2 in immunoglobulin A (IgA) nephropathy (n=42), and 33.0+/-33.8 cells/mm2 in diabetic nephropathy (n=10). Except for patients with the rapidly progressive glomerulonephritic syndrome (RPGN), the number of infiltrating mast cells significantly correlated with the serum concentration of creatinine at the time of renal biopsy (r=0.59; P < 0.0001) and with the intensity of tubulointerstitial injury as measured by leukocyte infiltration (r=0.72; P < 0.0001) and fibrosis (r=0.75; P < 0.0001). In contrast, mast cell infiltration did not correlate with urinary protein excretion. In relation to serum creatinine concentration, the number of mast cells was fewer in patients with RPGN than in those with chronic glomerulonephritis. These data suggest that mast cells may contribute to the renal deterioration in glomerulonephritis by inducing chronic tubulointerstitial injury.     

HBV-GN肾小管间质损害的发生影响因素及临床意义

目的:探讨乙肝相关性肾炎(HBV-GN)中肾小管间质损害(TIL)的发生情况、影响因素及临床意义。方法:单因素及多因素分析227例HBV-GN患者TIL发生的影响因素,比较不同程度TIL患者的临床病理资料。结果:肾小管间质损害轻度者占59.5%,中度者占17.6%,重度者占4.8%,无肾小管间质损害者仅占18.1%。不同病理类型HBV-GN患者其TIL发生率各不相同,年龄>14岁、高血压、尿蛋白≥0.3g/d、血肌酐≥132.6μmol/L、球囊黏连、新月体形成、系膜增殖程度和肾小球硬化率是TIL发生的危险因素,其中高血压、系膜增殖程度和肾小球硬化率是TIL发生的独立影响因素;随着肾小管间质损害的发生或加重,尿蛋白≥0.3g/d、高血压、高尿酸血症、肾功能异常和上述4种肾小球病理改变的发生率亦增高。结论:肾小管间质损害在HBV-GN患者的十分常见,高血压、系膜增殖程度和肾小球硬化率是TIL的独立危险因素,TIL发生或加重对其肾小球病理改变也有明显影响,是影响HBV-GN预后的不良因素之一。     

The role of myofibroblasts and interstitial fibrosis in the progression of membranous nephropathy

Renal interstitial fibrosis has been observed in a large number of nephropathies and contributes to the progressive deterioration of renal function. Myofibroblasts have been implicated in the reparative process of tissue injury, including renal scarring secondary to glomerular diseases. We performed a retrospective study on 28 patients with biopsy-proven primary membranous nephropathy, to determine whether interstitial myofibroblasts and tubulointerstitial lesions correlated with renal function at follow-up. Tubulointerstitial pathology was evaluated by morphometric and semiquantitative methods. Interstitial myofibroblasts were counted; 24-hour urinary protein and serum creatinine at the time of diagnosis and at the end of follow-up were available for all the patients. There were 20 males and 8 females, age 2-67 years (mean 42.3+/-15.3), most of them with nephrotic syndrome (78.6%). The final renal function had deteriorated in 16 patients (57.1%) and in 5 patients (17.8%) reached end-stage. The renal outcome was correlated with histological changes. We found a positive correlation between the severity of tubulointerstitial damage and the deterioration of the final serum creatinine (r2=0.185; p=0.016). Myofibroblasts did not predict impaired renal function at the final follow-up. The current data do not support previous suggestions that myofibroblasts are a useful a predictor of end-stage renal disease.     

Tissue-specific expression of renin-angiotensin system components in IgA nephropathy

BACKGROUND: The renin-angiotensin II system (RAS) has been implicated in the development of glomerulonephritis. The aims of this study were to determine (1) the expression of RAS components, angiotensin (Ang II)-forming enzymes [angiotensin-I-converting enzyme (ACE) and chymase], and Ang II receptors, and (2) the correlation between RAS expression and severity of tissue injury in IgA nephropathy (IgAN). METHODS: The expression levels of ACE, chymase, and Ang II type 1 and type 2 receptor (AT1R and AT2R) mRNAs were determined by in situ hybridization in renal specimens from 18 patients with IgAN, 5 patients with non-IgA mesangial proliferative glomerulonephritis (non-IgAN) and 10 patients with nonmesangial proliferative glomerulonephritis (minimal change nephrotic syndrome, n = 5, and membranous nephropathy, n = 5). Normal portions of surgically resected kidney served as control. RESULTS: In normal kidney, a few mesangial cells and glomerular and tubular epithelial cells weakly expressed ACE, chymase and AT1R mRNAs. In IgAN and non-IgAN samples, ACE, chymase, AT1R and AT2R mRNAs were expressed in resident glomerular cells, including mesangial cells, glomerular epithelial cells and cells of Bowman's capsule. The glomerular expressions in IgAN were stronger than in minimal change nephrotic syndrome and membranous nephropathy. In IgAN, the expressions in glomeruli correlated with the degree of mesangial hypercellularity, whereas the expression levels were weaker at the area of mesangial expansion. IgAN with severe tubulointerstitial injury showed expression of ACE, chymase, AT1R and AT2R mRNAs in atrophic tubules and infiltrating cells and such expression correlated with the degree of tubulointerstitial damage. CONCLUSION: Our results suggest that renal cells can produce RAS components and that locally synthesized Ang II may be involved in tissue injury in IgAN through Ang II receptors in the kidney.     

Predominant tubulointerstitial nephritis in a patient with systemic lupus nephritis

In most cases of systemic lupus erythematosus (SLE), glomerular lesions are the main renal complication. Although tubulointerstitial lesions are often associated with severe glomerular lesions, predominant or isolated tubulointerstitial injury in the presence of minimal glomerular abnormalities with SLE, so-called predominant tubulointerstitial lupus nephritis, is rare. Only ten cases are reported in the English literature. Herein, we describe the case of a 64-year-old man with SLE who presented with acute renal deterioration attributable to acute tubulointerstitial nephritis. Renal biopsy showed diffuse infiltration of inflammatory mononuclear cells in the interstitium and tubulitis without significant glomerular lesions. Immunofluorescence study revealed positive staining for IgG, C3, and C1q along the renal tubular basement membrane (TBM). Electron microscopy also showed electron-dense deposits in the TBM. Other causes of tubulointerstitial injury, such as drug use and infection, were ruled out. Taking these findings together with the presence of antitubular basement membrane antibody, predominant tubulointerstitial lupus nephritis was diagnosed. Treatment with oral corticosteroids for 6 weeks improved renal function. Even after tapering of the corticosteroid, renal function and serological markers of SLE activity have remained stable in this patient for more than 12 months.     

高尿酸血症与IgA肾病临床和病理表现的关系

目的分析IgA肾病合并高尿酸血症患者的临床和病理特征。方法将228例IgA肾病患者分为血尿酸正常组（154例）和高尿酸血症组（74例）,回顾性分析2组患者的年龄、血尿酸、估算肾小球滤过率（eGFR）、24h尿蛋白定量、总胆固醇（Tc）、血白蛋白（Alb）以及肾脏病理改变的差异。结果与血尿酸正常组相比,高尿酸血症组的尿蛋白明显增多（P〈0．01）,eGFR显著降低（P〈0．01）,肾小球球性硬化比率显著升高（P〈0．05）,肾小球细胞增殖程度和。肾小管间质损伤程度显著加重（P〈0．0B）,肾内动脉病变的发生率显著增高（P〈0．05）。Spearman相关分析显示,eGFR与肾小球硬化的比例呈负相关（r=-0．308、P〈0．01）、与肾小球细胞增殖程度呈负相关（r=-0．170,P〈0．01）、与肾小管间质受损的程度呈负相关（r=-0．409,P〈0．01）;而血尿酸与肾小球硬化的比例呈正相关（r=0．147,P〈0．05）、与。肾小球细胞增殖程度呈正相关（r=0．193,P〈0．01）、与肾小管间质受损的程度呈正相关（r=0．219,P〈0．01）;24h尿蛋白定量与肾小球细胞增殖程度呈正相关（r=0．259,P〈0．01）、与肾小管间质受损的程度呈正相关（r=0．225,P〈0．01）。结论高尿酸血症与IgA肾病患者的临床和病理损害相关。     

Clinicopathologic study of glomerulonephritis showing double-contour lesions

Background To elucidate the pathologic significance of double-contour lesions of glomerular capillary walls, we determined how the clinical course of patients with diffuse and global double-contour lesions differs from that of patients with segmentally located double-contour lesions. Methods In 26 out of 308 cases of idiopathic glomerulonephritis double contour lesions and serum complement 3 (C3) deposition along capillary walls were histologically examined. Results Most patients with diffuse (affecting more than 80% of all glomeruli) and global (affecting more than 75% of each glomerulus) double-contour lesions exhibited a persistent profound proteinuria and a deterioration of renal function (assessed via serum creatinine measurements) during a mean observation period of 66 months, even when a transient remission was observed. The amelioration of hypocomplementemia correlated significantly with an improvement in proteinuria (P<0.05). A follow-up biopsy of patients revealed some cases in which there was: (1) no amelioration of the glomerular lesion despite improvements in renal function, proteinuria and hypocomplementemia; (2) an amelioration of the glomerular lesion paralleling an increasing stability in renal function and a reduction in proteinuria; or (3) deterioration of the glomerular lesion paralleling a decrease in renal function, an increase in proteinuria, and persistent hypocomplementemia. Conclusions These findings indicate that the clinical characteristics of mesangiocapillary glomerulonephritis differ from those of other types of mesangial proliferative glomerulonephritis with segmentally-located double-contour lesions. A spot, unrepeated biopsy in cases of atypical mild mesangiocapillary lesions provides insufficient information to reach a diagnosis of mesangiocapillary glomerulonephritis.     

Long-term outcome of adult patients with minimal urinary abnormalities and normal renal function.

AIM: To define the long-term outcome of patients with minimal urinary abnormalities (defined by the presence of microscopic hematuria with no or less than 1 gm/day proteinuria), and normal renal function (defined by a serum creatinine < 1.3 mg/dl), we retrospectively studied patients who fulfilled the above criteria and had a kidney biopsy done before the year of 1992 (i.e. at least followed up for 5 years), with a definite pathological diagnosis. METHODS: A total of 41 cases among 719 cases of primary glomerulonephritis (5.7%) were enrolled into the study. There were 19 males and 22 females with a mean age of 35.4+/-14.7 years at biopsy. The duration of renal disease was 116.0+/-60.5 months and the duration of follow-up post biopsy was 100.2+/-38.1 months. The pathological diagnosis was: IgA nephropathy (21 cases), focal glomerulosclerosis (9 cases), mesangial proliferative glomerulonephritis (8 cases), membranous glomerulonephritis (2 cases) and acute glomerulonephritis (1 case). RESULTS: At the end of follow-up, 8 cases (19.5%) had a certain degree of renal insufficiency including 2 (4.9%) in end-stage renal disease. The other cases were either in complete remission (6 cases) or stable condition (27 cases) with persistent microscopic hematuria and normal renal function. The long-term outcome was not correlated with any of the following parameters: age, sex, disease duration, serum creatinine at presentation, daily protein loss at presentation, degree of glomerular change and degree of interstitial inflammatory cell infiltration. However, a poor long-term outcome was correlated with tubular atrophy (p < 0.05) and interstitial fibrosis (p < 0.05). CONCLUSION: We conclude that a minimal urinary abnormality with normal renal function at presentation does not necessarily imply a favorable long-term outcome in certain patients. Tubular atrophy and interstitial fibrosis but not glomerular change correlates with a worse prognosis. This further emphasizes the importance of renal biopsy in such cases.     

Association of angiotensin-converting enzyme gene polymorphism and renal pathology in Japanese children with IgA nephropathy.

Polymorphism of the gene that codes for angiotensin I-converting enzyme (ACE) is associated with increased severity of immunoglobulin A (IgA) nephropathy in adult patients. We evaluated the relationship between the polymorphism of ACE genotypes and the pathological and clinical findings in Japanese children with IgA nephropathy. Patients with moderate/diffuse mesangial proliferation, glomerular sclerosis and tubulointerstitial damage showed a significant increase of the D/D type compared to those who had mild/focal mesangial proliferation, without glomerular sclerosis or tubulointerstitial damage (p < 0.05). Proteinuria at the first renal biopsy was significantly higher in the former group compared with the latter group except glomerular sclerosis (p < 0.01). IgA nephropathy patients with tubulointerstitial damage also showed an increased serum creatinine level compared to patients without the damage (p < 0.03). We conclude that ACE gene polymorphism may be correlated with the prognosis of IgA nephropathy in Japanese children.     

Prognostic indicators in childhood IgA nephropathy.

A number of clinical, laboratory and pathologic parameters were assessed for their prognostic significance in 200 children aged less than 15 years with IgA nephropathy, who had shown normal renal function at the time of initial biopsy and were followed for more than 2 years thereafter. After a mean follow-up period of 5.0 years from the initial biopsy, 93 patients had no demonstrable abnormality, 76 had minor urinary abnormalities, 21 had persistent heavy proteinuria and 10 had developed chronic renal impairment. A poor outcome was found to be correlated with heavy proteinuria at biopsy, diffuse mesangial proliferation, a high proportion of glomeruli showing sclerosis, crescents or capsular adhesions, the presence of moderate or severe tubulointerstitial changes, and the presence of subepithelial electron-dense deposits and lysis of the glomerular basement membrane by electron microscopy. The percentage of glomeruli displaying crescents, sclerosis and adhesions appeared to be the most reliable prognostic indicator. Nine of the 27 patients (33%) in whom greater than or equal to 30% of glomeruli showed crescents, sclerosis and adhesions developed chronic renal impairment, and only 14% of these patients had normal urine at follow-up. In contrast, only 1 of the 173 patients in whom less than 30% of glomeruli showed such lesions developed chronic renal impairment (p less than 0.001) and 51% of these patients showed complete remission at follow-up (p less than 0.001). These results demonstrate that an accurate prediction of the outcome based on the initial renal biopsy findings is possible early in the course of children with IgA nephropathy.     

Epidemiology of idiopathic glomerular disease: a prospective study

In this study incidence rates of idiopathic glomerular disease in 1.5 X 10(6) Dutch adults between 16 and 65 years of age were determined, as well as the prevalence of these diseases in terms of indication for renal biopsy. The study was conducted between 1978 and 1985; indications for renal biopsy in decreasing hierarchical order were recently discovered uremia, nephrotic syndrome, chronic hematuria of less than two years duration with or without proteinuria or disturbed renal function, and chronic proteinuria of less than two years duration, of unknown origin. The main findings are fourfold. The incidence of IgA nephropathy and thin glomerular basal membrane lesions was high, 19 and 13 per 10(6) adults respectively, and the prevalence in patients biopsied because of non-azotemic chronic hematuria was 31% and 22%, respectively. In the normotensive non-azotemic adults biopsied because of chronic, mild proteinuria the prevalence of focal segmental glomerular sclerosis and vascular hyalinosis was both 41%. Of the patients biopsied because of nephrotic syndrome the prevalence of membranoproliferative glomerulonephritis (5%) was low, as was the incidence (less than 2 per 10(6) adults per year). Finally, the prevalence of diffuse sclerosing glomerulonephritis was 25% in patients biopsied because of uremia. This study is useful for the differential diagnosis of idiopathic glomerular disease.     

Tubulointerstitial disease in lupus nephritis: relationship to immune deposits, interstitial inflammation, glomerular changes, renal function, and prognosis

The interrelationships between tubulointerstitial immune deposits (TID), interstitial inflammation, glomerular changes, renal function, and prognosis were assessed in the renal biopsies from 93 patients with lupus nephritis. The prevalence of TID was 33% by immunofluorescence and 23% by electron microscopy. Although predominantly detected along and within tubular basement membranes, extraglomerular immune deposits were also present in the wall of renal interstitial capillaries and small arteries as well as in Bowman's capsule. The prevalence of TID correlated with the activity of glomerular lesions and, to a lesser extent, with the severity of proliferative lupus nephritis (WHO classes II-IV). TID were much less common in the membranous form (WHO class V). The severity of interstitial inflammation correlated with the degree of renal insufficiency and was an accurate prognostic indicator of progressive deterioration of renal function. However, there was no correlation between prevalence of TID and prevalence and severity of interstitial inflammation, suggesting that the latter is not necessarily secondary to the presence of immune complexes and that other pathogenetic mechanisms may be involved.     

原发性肾病综合征患者IL-18的血浆水平及其在肾组织的表达

目的：初步探讨白细胞介素18(IL—18)在原发性肾病综合征(PNS)发生发展中的作用。方法：采用酶联免疫吸附(ELISA)法测定11例正常人及24例PNS患者血浆IL—18水平，同时用免疫组织化学方法检测6例正常肾组织和上述24例PNS患者肾组织IL—18的表达量。结果：PNS患者血浆IL—18水平与正常对照组IL较无统计学意义；而且各种病理类型间的差异也没有统计学意义(P均＞0．05)；而肾小球及肾小管—间质IL—18表达量却均显著高于正常对照组(P均＜0．01)。不同病理类型PNS肾小球区IL—18表达量存在差异，以膜增生性肾小球肾炎(MPGN)表达量为最高，其次为系膜增生性肾小球肾炎(MesPGN)，而膜性肾病(MD)、局灶节段性肾小球硬化(FSGS)和轻微病变(MCD)的表达量则相对较低，并且肾小球区IL—18表达量与24h尿蛋白排泄量(24h　UPQ)至正相关，与血浆白蛋白浓度(Alb)至负相关(r分别为0．669和－0．727，P均＜0．01)；肾小管—间质区IL—18表达量与小管—间质损害程度至正相关(r＝0．484，P＜0．05)。结论：肾组织IL—18高表达可能参与PNS的发病过程，而又可能以自分泌或/和旁分泌方式起作用。     

不同病理类型肾病患者蛋白尿成分与肾脏病理的关系

目的 探讨不同病理类型原发性肾小球肾炎 (PGN) 患者的尿蛋白成分与肾脏病理的关系。 方法 对象为117例PGN患者。采用散射比浊法行尿蛋白成分分析。检测患者的Scr、24 h尿蛋白量。将上述指标与肾脏病理评分进行统计学分析。结果 轻微病变(MCD)患者尿白蛋白(Alb)浓度最高；尿β2微球蛋白(β2-MG)以硬化性肾小球肾炎(SGN)患者最高。在肾小管间质评分中，尿IgG/总蛋白(IgG/Tpro)、尿转铁蛋白(TRF)和β2-MG是主要的相关因子，而IgG/Tpro与肾小球硬化有相关性。尿TRF和β2-MG分别是IgA肾病(IgAN)和MCD患者肾小管间质损害评分的重要影响因子。尿TRF、IgG、λ轻链和β2-MG是影响膜性肾病(MN)肾小管间质损害评分的重要因素。结论 不同病理类型的PGN患者尿蛋白组成有差异，尿IgG、尿转铁蛋白及β2-MG浓度与肾小管间质损害的关系密切。     

Long-term prognosis of membranoproliferative glomerulonephritis type I. Significance of clinical and morphological parameters: an investigation of 220 cases

We carried out a retrospective investigation in 220 patients to assess the influence of various parameters on the long-term course of membranoproliferative glomerulonephritis (MPGN) type I. 50 patients (23%) died during the follow-up period of 59 months on average, in another 57 (26%) end-stage renal failure developed. 54 patients (24%) suffered from chronic renal failure, stable renal function (creatinine below 1.3 mg/dl) was preserved in 59 patients (27%). 5 years after biopsy 49% of the patients had already died or needed regular dialysis treatment; after 10 years this proportion increased to 64%. Morphological findings: The outcome was--with the exception of focal crescent formations--not determined by the severity of glomerular changes; the survival rate, however, decreased significantly, if tubulointerstitial lesions were present as defined by acute renal failure, interstitial fibrosis or a combination of both. Clinical parameters: A progressive deterioration of renal function and an increasing number of renal deaths was noticed, when elevated serum creatinine levels at the time of biopsy and high blood pressure values during the follow-up period were observed. 26 patients died from hypertension, 18 of whom before reaching end-stage renal failure. Nephrotic syndrome and the degree of proteinuria as well as antiphlogistic and immunosuppressive treatment did not influence the prognosis of MPGN type I.     

贫血加重IgA肾病患者的临床和病理改变

目的 分析IgA肾病合并贫血患者的临床病理特征.方法 收集经肾活检确诊的IgA肾病患者临床资料409例,按照贫血与否分为非贫血组和贫血组,回顾性分析两组患者的临床和病理资料.结果 与非贫血组比较,贫血组患者的肾小球损伤和肾小管间质萎缩程度较重、24 h尿蛋白增多和eGFR降低.Spearman相关分析结果显示,血红蛋白、eGFR与肾脏病理损伤呈负相关(P＜0.05),血尿酸、24h尿蛋白与肾脏病理损伤呈正相关(P＜0.05).多因素Logistic回归分析发现贫血是肾小管间质萎缩的独立危险因素.结论 IgA肾病合并贫血患者的临床和病理损伤重于IgA肾病非贫血的患者,贫血参与IgA肾病的进展.     

Tubulointerstitial injury in glomerulonephritis

Summary: It is now widely accepted that tubulointerstitial lesions correlate with renal function in glomerulonephritis and that the severity of such lesions predicts disease progression. Interstitial leucocytic infiltration is a prominent feature of tubulointerstitial lesions which also correlates with renal function and outcome in human glomerulonephritis, while intervention studies in animal disease models have demonstrated a causal role of these cells in progressive tubulointerstitial injury. This paper focuses on two aspects of immune-mediated tubulointerstitial injury. First, the development of interstitial leucocytic infiltration and the relationship between periglomerular leucocytes and Bownman's capsule integrity, and second, the concept that tubular cells are not only passive targets of injury in glomerulonephritis, but that they actively participate in the immune/inflammatory process.     

The role of alpha-smooth muscle actin and platelet-derived growth factor-beta receptor in the progression of renal damage in human IgA nephropathy

BACKGROUND: The degree of tubulointerstitial damage can be considered a better indicator of renal function outcome in IgA nephropathy (N) than the extent of glomerular sclerosis. MATERIALS AND METHODS: To investigate the pathogenetic mechanisms of interstitial injury in IgAN, we used immunohistochemistry and in situ hybridization to evaluate the glomerular and tubolointerstitial expression of PDGF-beta receptor (R) and alpha-smooth muscle actin (SMA), two markers of mesenchymal cell activation, and correlated these findings with the histopathologic and clinical features of the disease. We studied 155 IgAN patients, divided into three groups based on the histological findings (mild, moderate and severe histological lesions). RESULTS: In normal kidneys and in patients with mild histological lesions, the interstitial areas showed scattered peritubular cells positive for PDGF-betaR and alpha-SMA, with a distribution resembling the capillary network. In the glomeruli several cells (mainly in the mesangial area) stained for PDGF-betaR, but only very few cells were positive for alpha-SMA. Alpha-SMA and PDGF-betaR staining, as expected, was also observed in vascular smooth muscle cells. Compared to patients with mild histological lesions, alpha-SMA expression was strikingly increased in patients with moderate to severe lesions, particularly in areas of tubulointerstitial fibrosis. In these patients, PDGF-betaR gene and protein expression, at the tubulointerstitial level, paralleled that in alpha-SMA. Both signals were significantly correlated with the interstitial damage (interstitial infiltrate and fibrosis). Interestingly, these patients showed a different pattern of distribution of alpha-SMA and PDGF-betaR in the glomeruli: PDGF-betaR expression was upregulated, whereas no changes were seen in alpha-SMA staining. In addition, glomerular PDGF-betaR staining was significantly correlated with mesangial cell proliferation, while alpha-SMA was not. Image analysis showed that 40.2+/-10.3/1,000 microm2 of interstitial cells were positive to both PDGF-betaR and alpha-SMA, but only 2.8+/-1.8/1,000 microm of glomerular cells expressed both signals. CONCLUSIONS: Our study supports the hypothesis that interstitial PDGF-betaR and alpha-SMA positive cells may play a key role in the pathogenesis of tubulointerstitial damage.     

Evaluation of tubulointerstitial injury by Doppler ultrasonography in glomerular diseases

AIMS: While Doppler ultrasonography is used commonly in various renal diseases, its clinical value in diagnosis of renal parenchymal diseases, especially glomerular diseases, remains controversial. We investigated whether Doppler ultrasonography in glomerular diseases could discriminate tubulointerstitial lesions, which correlated closely with long-term prognosis for renal function. METHODS: Sixty patients with primary or secondary glomerular diseases were examined by Doppler ultrasonography immediately before renal biopsy. The resistive index was calculated, as was the atrophic index (a newly proposed parameter defined as renal sinus length/renal length). These were compared with histologic changes in biopsy specimens. RESULTS: Receiver operator characteristic analysis showed a resistive index of 0.65 to be the optimal for discriminating tubulointerstitial changes with specificity of 100% and sensitivity of 57.1%. Tubulointerstitial injury scores were significantly higher in patients with resistive indices exceeding 0.65 than in patients with a lower value. An atrophic index of 0.70 was also shown to be optimal with specificity 100% and sensitivity 61.9%. In combination, the 2 indices showed improved sensitivity; when the patients were divided into groups where both resistive and atrophic indices were normal (respectively < or = 0.65 and < or = 0.70) or where either or both were high, sensitivity rose to 85.7%, while specificity remained 94.4%. CONCLUSIONS: In combination, the resistive and atrophic indices discriminated tubulointerstitial injury in glomerular diseases with high specificity and sensitivity.     

50例急性肾衰竭患者尿沉渣镜检与肾活检病理对比分析

目的探讨尿沉渣谱是否能反映急性肾衰竭患者肾脏病理损伤。方法50例急性肾衰竭患者以肾活检病理为评估金标准。取肾活检日晨尿，由专人双盲用相差显微镜检测。根据肾脏病理结果将患者分为3组：以肾小球增殖性病变为主、非增殖性病变为主和小管间质病变为主。尿沉渣所见包括红细胞、有核细胞和各种管型，也分为3类沉渣谱：Ⅰ类以变形红细胞和红细胞管型为主的多种细胞、多种管型，伴蛋白尿；Ⅱ类呈少细胞、细颗粒或透明管型中镶嵌有核细胞，伴大量尿蛋白；Ⅲ类少细胞、透明管型为主或其中嵌入几个有核细胞，蛋白量少。比较不同病理改变的尿沉渣特点。结果肾小球增殖性病变为主33例中30例（91％）为Ⅰ类尿沉渣谱；肾小球非增殖性病变为主9例中8例为Ⅱ类尿沉渣谱；小管间质病变为主8例中5例为Ⅲ类尿沉渣谱。结论尿沉渣分析能在一定程度上反映肾损伤的部位和严重性，这项无创、经济、方便的检查方法值得临床重视与应用。