Morphometric insights into nephrotic syndrome in children: Are we any wiser?

Summary: The present study was undertaken in the hope that conflicting opinions concerning interrelationships among minimal change disease (MCD), mesangial proliferative glomerulonephritis (MPG) and focal segmental glomeruloscierosis (FSGS) might be elucidated by morphometric methods performed by image analysis, as well as to study whether serum creatinine and changes in quantitatively analysed glomeruli could correlate with the interstitial fibrosis in these glomerulopathies. Fifteen renal biopsy specimens from children with MCD, 10 with primary MPG and 12 with FSGS for whom both light and electron microscopy as well as immunofluorescence microscopy and full clinical data were available, were examined quantitatively. As a control five biopsy and 10 autopsy specimens of the normal kidneys were used. Our quantitative study showed that in MCD, MPG and FSGS glomerular and interstitial values differed from normal. Morphometric differences between MPG and both MCD and FSGS groups were also shown. Although the mean values of total glomerular area and relative interstitial volume were increased in FSGS patients, in total glomerular cells per unit of glomerular area and mesangium (% of total glomerular area) were similar in both MCD and FSGS groups. In MPG strong positive correlations existed between interstitial volume and serum creatinine, interstitial volume and total glomerular cells per unit of glomerular area as well as between interstitial volume and glomerular mesangium (% of total glomerular area). In FSGS there was significant positive correlation between interstitial volume and serum creatinine. In the MCD group all correlations were weak and not significant. In conclusion, our morphometric studies suggest a close relationship between MCD and FSGS, and indicate that MPG is a separate morphologic entity in children.     

SOD复合酶对大鼠急性肾小球肾炎保护作用的实验研究

研究超氧化物歧化酶复合酶在急性肾小球肾炎病程中对组织结构和功能的保护 作用。方法诱发大鼠急性肾小球肾炎，并肌注ＳＯＤ复合酶抗氧化保护性治疗。     

原位PCR检测肾组织内的乙型肝炎病毒

采用原位ＰＣＲ技术检测了肾小球肾炎患者活体组织。证实乙型肝炎病毒＜ＨＢＶ＞相关性肾脏中ＨＢＶ的存在。从分子病理学水平为探讨ＨＢＶ相关性肾炎发病机理提供了新的依据。     

In vivo gene transfer: focus on the kidney

Renal gene transfer techniques are being developed as a novelexperimental approach to understand the pathogenesis of renaldisease and to potentially develop new therapeutic tools. Wereview the currently available technology to introduce foreigngenetic material into renal tissue, i.e., retroviral, adenoviral,and liposomal transfer systems with their respective advantagesand caveats. Today, the transfer efficiency of these methodsappears to be sufficiently high to study the effects of transducedgenes on renal function and morphology in rat kidney. This willallow (i) the elucidation of the function of genes on the courseof renal disease in experimental animal models and (ii) themodulation of local expression of endogenous genes which presumptivelycontribute to renal pathology in these models. One strategyto accomplish this aim is the use of recombinant DNA technologyto design antisense DNA constructs or oligonucleotides, whichinterfere with the renal expression of target genes. We willalso discuss some of the shortcomings of the currently usedtechniques with respect to potential therapeutic use of genetransfer systems and gene modulation.     

Role of mast cells in experimental anti-glomerular basement membrane glomerulonephritis

Recently, divergent reports on the role of mast cells (MC) in different glomerular diseases have brought our attention to their role in an accelerated model of anti-glomerular basement membrane (GBM) glomerulonephritis (GN). Genetically MC-deficient Kit(W)/Kit(W-v) mice, MC-reconstituted Kit(W)/Kit(W-v) mice and Kit+/+ control mice were subjected to anti-GBM GN. Kit(+/+) mice developed moderate proteinuria and glomerular damage following the induction of anti-GBM nephritis. In contrast, proteinuria and glomerular damage were dramatically increased in MC-deficient Kit(W)/Kit(W-v) mice. MC-reconstituted Kit(W)/Kit(W-v) mice showed proteinuria and glomerular damage comparable to Kit+/+ mice. A significant increase in infiltrating T cells and macrophages was detected in MC-deficient Kit(W)/Kit(W-v) mice as compared to Kit+/+ control mice and MC-reconstituted Kit(W)/Kit(W-v) mice. Accordingly, we observed an increase of TGF-beta1 mRNA in kidneys from Kit(W)/Kit(W-v) mice. Interestingly, we did not detect MC in the kidney using either Giemsa staining or RT-real-time PCR, but MC were found in the regional lymph nodes. Finally, mortality of Kit(W)/Kit(W-v) mice was significantly increased after the induction of anti-GBM GN due to uremia. Our report provides the first direct evidence that MC are protective in anti-GBM GN, possibly by modulating the influx of effector T cells and macrophages to inflammatory sites in the kidney.     

Alpha-SM actin expression as prognostic indicator in IgA nephropathy (Berger's disease)

Recent studies have demonstrated that α-Smooth Muscle actin expression in glomerular and tubulointerstitial compartments of renal tissue could represent a prognostic marker in several renal diseases. Our objective was to identify the prognostic value of α-SM actin actin expression on the evolution of renal damage in Primary IgA nephropathy (Berger’s Disease). 43 patients followed up from 1988 to 1999 at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil, was studied. Clinical-laboratory data were obtained from the medical records of the patients using a protocol containing name, race, gender, origin, profession, age at clinical presentation of the disease and personal and family history. The parameters assessed in the approach to IgA nephropathy were serum creatinine, creatinine clearance, serum albumin, total serum protein, 24 hours proteinuria, glycaemia, serum sodium, potassium, calcium and phosphorus ions, analysis of urinary sediment, serum complement profile, blood count, and renal biopsy. Morphological evaluation was performed by renal biopsy using common light and immunofluorescence microscopy. Immunohistochemical studies were performed using a murine monoclonal antibody to α-SM actin. Our data showed that α-SM actin expression in the glomerular and tubulointerstitial compartments are not correlated with unfavorable clinical course of primary IgA nephropathy.     

Mononuclear-cell subsets in human idiopathic crescentic glomerulonephritis (ICGN): Analysis in tissue sections with monoclonal antibodies

Mononuclear inflammatory cells (MIC) were analyzed in renal biopsies from 16 patients with ICGN (7 with glomerular immune complex deposits, 3 with anti-GBM disease, and 6 without immune deposits) by the avidin-biotin-immunoperoxidase technique utilizing monoclonal antibodies to cell surface antigens: T11 (total T), T4 (inducer/helper T), T8 (suppressor/cytotoxic T), B1 (B cells), M1 (monocytes/granulocytes), and Leu 7 [natural killer (NK) cells]. Total MIC were significantly increased in both glomeruli and interstitial tissues of the patients. Interstitial MIC consisted mainly of lymphocytes (80%) and monocytes (19%), with small numbers of B and NK cells present. In contrast, MIC in renal glomeruli of patients with ICGN were composed of monocytes (65%) rather than T lymphocytes (34%). A majority of T lymphocytes found in renal tissues of patients and controls had the helper/inducer phenotype. Tissue T4/T8 ratios were not significantly different in the glomeruli and interstitium. Monocytes and T lymphocytes accumulating in renal tissues of patients with ICGN may mediate glomerular injury in all forms of human ICGN.Presented in part at the 15th Annual Meeting of the American Society of Nephrology, Chicago, Illinois, 1982.     

Lack of directed Vα14-Jα281 rearrangements in NK1+ T cells

NK1.1⁺ T cells are an unusual subset of TCRαβ cells distinguished by their highly restricted Vβ repertoire and predominant usage of an invariant Vα14-Jα281 chain. To assess whether a directed rearrangement mechanism could be responsible for this invariant α chain, we have analyzed Vα14 rearrangements by polymerase chain reaction and Southern blot in a panel of cloned T-T hybrids derived from thymic NK1.1⁺ T cells. As expected a high proportion (17/20) of the hybrids had rearranged Vα14 to Jα281. However, Vα14-Jα281 rearrangements always occurred on only one chromosome and were accompanied by other Vα-Ja rearrangements (not involving Vα14) on the homologous chromosome. These data argue that rigorous ligand selection rather than directed rearrangement is responsible for the high frequency of Vα14-Jα281 rearrangements in NK1.1⁺ T cells.     

巨噬细胞移动抑制因子在非IgA系膜增生性肾小球肾炎肾组织中的表达

目的 探讨巨噬细胞移动抑制因子（MIF）在非IgA系膜增生性肾小球肾炎患者肾组织中的表达及其意义。方法 应用免疫组织化学双标记技术检测正常对照组及不同病变程度非IgA系膜增生性肾小球肾炎患者肾组织内MIF和人巨噬细胞标记抗原CD68的表达。结果 在正常对照组和IgA系膜增生性肾小球肾炎患者轻度组仅有少量MIF和CD68表达。随着非IgA系膜增生性肾小球肾炎病变程度的加重,MIF、CD68的表达逐渐增强,重度病变时,MIF、CD68的表达最强,且MIF表达水平与CD68表达呈正相关（r=0.87,P〈0.01）。结论 肾组织内MIF表达上调所导致的巨噬细胞浸润增加可能是非IgA系膜增生性肾小球肾炎进展的重要机制之一。     

Monocytes secrete factors regulating glycosaminoglycan synthesis in mesangial cells in vitro.

The present study was conducted to determine the manner in which monocytes increase mesangial matrices, particularly glycosaminoglycans (GAGs) which interact with various other matrix components such as collagens, laminin, fibronectin and lipoproteins. A supernatant of human peripheral blood monocyte cultures activated by lipopolysaccharide (LPS) contains stimulating factors for glycosaminoglycan synthesis in rat mesangial cells (MCs). The culture supernatant in this study was concentrated and fractionated by gel chromatography and the GAG-stimulatory factor was found to have a molecular weight of 10-17 kD. This factor was shown to be present in fractions different from that of IL-1. Gel and ion-exchange chromatography studies of GAGs synthesized by MCs indicated the elution patterns of GAGs in the presence and absence of the monocyte culture supernatant to be essentially the same. Local infiltration of monocytes into the glomerulus, often seen in various types of glomerular injury, may be an important factor in the accumulation of the mesangial matrix.