Focal Glomerulosclerosis Patients Research Articles

Urinary liver-type fatty acid-binding protein levels for differential diagnosis of idiopathic focal glomerulosclerosis and minor glomerular abnormalities and effect of low-density lipoprotein apheresis

Focal glomerulosclerosis (FGS) and minor glomerular abnormalities are kidney diseases characterized by massive proteinuria. Urinary liver-type fatty acid-binding protein (L-FABP), an intracellular carrier protein of free fatty acids, is expressed in proximal tubules of the human kidney. Patients with FGS show significant improvement with low-density lipoprotein (LDL) apheresis. The aim of the present study was to determine whether urinary L-FABP levels differ between patients with FGS and those with minor glomerular abnormalities and whether levels are altered by LDL apheresis. There were 24 patients with minor glomerular abnormalities (nephrotic stage, n = 14, remission stage, n = 10), 17 patients with FGS, and 20 healthy age-matched subjects were included in the present study. Urinary L-FABP levels were measured by enzyme-linked immunosorbent assay and compared. All patients with minor glomerular abnormalities at the nephrotic stage received prednisolone for 6 months, and all FGS patients received some form of immunosuppression therapy with prednisolone, cyclophosphamide or mizoribine for 12 months. LDL apheresis was performed in eight FGS patients with drug-resistant nephrotic syndrome. Urinary L-FABP levels were significantly higher in the 17 FGS patients (82.0 +/- 44.4 microg/g.Cr) than in the 24 patients with minor glomerular abnormalities (10.2 +/- 8.4 microg/g.Cr) (p < 0.01) and in the 20 healthy subjects (7.4 +/- 4.2 microg/g.Cr) (p < 0.01). Urinary L-FABP levels differed little between nephrotic stage and remission stage in patients with minor glomerular abnormalities. Urinary L-FABP levels were significantly higher in the eight drug-resistant FGS patients (122.6 +/- 78.4 microg/g.Cr) than in the nine drug-sensitive FGS patients (45.9 +/- 32.0 microg/g.Cr). Urinary L-FABP levels did not correlate with levels of other clinical markers including serum creatinine, urinary protein, and urinary N-acetyl-beta-D- glucosaminidase. In the eight drug-resistant FGS patients, LDL-apheresis significantly reduced urinary protein excretion (p < 0.01) and urinary L-FABP levels (p < 0.01). Urinary L-FABP may be a useful diagnostic indicator for differentiation between FGS and minor glomerular abnormalities. LDL apheresis may be effective in ameliorating tubulointerstitial lesions associated with FGS.

Jak3 expression in glomerular epithelia of IgA nephropathy (IgA-N) patients.

Jak3 is a member of the Janus kinase family which plays an important role in cytokine signal transduction. Jak3 associates the gamma(c) chain of receptors for IL-2, IL-4, IL-7, IL-9 and IL-15, and is essential for the signal transduction of these cytokines. We have isolated Jak3 kinase from renal mesangial cells and demonstrated the constitutive expression of Jak3 in glomeruli in vivo. To investigate the physiological and pathological role of Jak3 in glomeruli, we prepared anti-Jak3 antibody and analysed the localization of Jak3 in glomeruli of renal biopsy samples from various nephritis patients and normal subjects. Among 61 nephritis patients and four normal subjects investigated in the present study, Jak3 was selectively localized to glomerular epithelia of IgA-N patients (14/34 cases) and focal glomerulosclerosis patients (1/5 cases), but not detected in minimal changes (n = 6), membranous glomerulonephropathy (n = 7), crescentic glomerulonephritis (n = 4), lupus nephritis patients (n = 5), and normal subjects (n = 4). The intense immunoreactivity for Jak3 is significantly associated with the decrease in creatinine clearance (81.5 +/- 10.4 ml/min versus 104.3 +/- 29.6 ml/min; P < 0.05, Student's t-test) and the increase in level of serum creatinine (1.13 +/- 0.33 mg/dl versus 0.75 +/- 0.23 mg/dl; P < 0.01, Student's t-test) in IgA-N patients. Furthermore, gamma(c) chain was concomitantly expressed with Jak3 in glomerular epithelia in vivo and in vitro, suggesting that signal transduction via gamma(c)-Jak3 cascade may be involved in the pathogenesis of glomerular injury of IgA-N. Taken together with the recent findings that IL-4-secreting T lymphocytes in affected glomeruli injure glomerular epithelium, the responsiveness of glomerular epithelium for IL-4 may be pathologically enhanced in IgA-N.

The Urinary Podocyte as a Marker for the Differential Diagnosis of Idiopathic Focal Glomerulosclerosis and Minimal-Change Nephrotic Syndrome

Background/Aims: Detection of podocytes in the urine sediment of children indicates that severe podocyte injury occurred in the glomerulus. Focal glomerulosclerosis (FGS) and minimal-change nephrotic syndrome (MCNS) are kidney diseases characterized by massive proteinuria. The aim of the present study was to determine whether urinary podocytes can be detected in patients with idiopathic FGS or MCNS and whether immunosuppression therapy alters these cells. Methods: Twenty patients with MCNS (nephrotic stage, n = 12; remission stage, n = 8), 15 patients with FGS and 20 healthy controls were included in the present study. Urinary podocytes were stained by immunofluorescence. All patients with MCNS at the nephrotic stage received prednisolone for 6 months, and all patients with FGS received some form of immunosuppression therapy including prednisolone, cyclophosphamide or mizoribine for 12 months. Results: The 12 nephrotic-stage MCNS patients achieved remission after treatment. Seven of the 15 FGS patients also achieved remission, but the other 8 remained in the nephrotic stage. Urinary podocytes were not detected in any patient with MCNS nor were they detected in healthy controls. Urinary podocytes were detected in all FGS patients (mean, 4.2 cells/ml) before treatment and the number of cells decreased in the 7 patients who achieved remission. The number of podocytes was unchanged in the other 8 patients even after treatment. Conclusion: Urinary podocytes may be a useful diagnostic indicator for differentiation between FGS and MCNS. These cells may also mark disease progression in cases of FGS.

A variety of clinical applicabilities of immobilized dextran sulphate as lipoprotein adsorbent and avoidance of anaphylactoid (anion-blood contact) reaction in its use.

Dyslipidemia including hyper-LDL(low density lipoprotein) cholesterol which is very often refractory to dietary/medical treatments is known to be a risk factor of many arteriosclerotic lesions. An extracorporeal procedure of plasma adsorption, LDL adsorption, utilizing dextran sulphate as a ligand immobilized on cellulose gel beads has been clinically applied in a variety of dyslipidemic conditions as listed below. Its usefulness in secure reduction of the serum LDL level and consequent symptomatic improvements has been confirmed. Familial hypercholesterolemia(FH): A regular repetition of the LDL adsorption ameliorates hyper-LDL cholesterolemia as resulting in regression of the multiple stenoses in the coronary arteries. Focal glomerulosclerosis(FGS): A seesion of the LDL adsorption improves kidney function and reduces a urinary protein excretion in FGS patients with dyslipidemia. Arteriosclerosis obliterans(ASO): More than 60 ASO patients with dyslipidemia have been treated by the LDL adsorption in our center. In over 80% of the patients, marked improvement in clinical symptoms such as leg pain/intermittent claudication has been brought out. Hemodialysis-relevant dyslipidemia(HDDL): HDDL which develops in the long-term HD patients has been treated. Transplantation-relevant dyslipidemia(TXDL): TXDL with deterioration of the transplanted kideny function has been treated by the LDL adsorption. Kidney function improves. Anaphylactoid reaction which is tentatively explained as a result of release of bradykinin in contact of blood with polyanionic material of the adsorbent, dextran sulphate, develops, in particular, while an angiotensin-converting enzyme inhibitor is administered as a depressant. However, it can be avoided in a use of nafmostat mesilate, a protease inhibitor, as an anticoagulant.

1639 EFFECT OF THE NEPHROTIC SYNDROME ON THE CONCENTRATION OF SERUM COMPLEMENT COMPONENTS

The concentration of twelve component and four control proteins of the complement system were measured in serum from 43 children with a nephrotic syndrome which subsequently proved to be steroid responsive and from 13 children with focal glomerulosclerosis (FGS) and compared to values from 197 normal subjects. Of classical pathway complement components, 40% of patients had low Clq and 20%, low C2 levels. Mean serum levels of Cls, C4, C1INH and C4bp were elev,ated. Of alternative pathway components, factors B and I were low in one-third while levels of C3 and H were commonly elevated. Of the terminal components, only C8 and C9 were low. In five FGS patients with hypoalbuminemia without edema, all component levels were normal. With the exception of C1q, C1s and C8, high molecular weight components were in high concentration and low molecular weight components in low concentration. The three exceptions may be explained by the sub-unit structure of C1 and C8. From a practical standpoint, the study indicates that edematous patients with a nephrotic syndrome may have low serum levels of C1q and C2, simulating classical pathway complement activation such as commonly occurs in glomerulonephritis. However, low levels of C4 and possibly C1s can be used as indicators of classical pathway activation since their levels are not reduced by a nephrotic syndrome.

1527 COAGULATION AND THE NEPHROTIC SYNDROME

The coagulation and fibrinolytic systems were studied in children with nephrotic syndrome using methods including plasma fibrinogen chromatography (Kid.Int.1976,10,319). Patients with minimal change disease (MCNS) were studied sequentially i) relapse on no treatment (n=34), ii) relapse receiving steroids (n=12), iii) early remission on steroids (n=14), iv) late remission on steroids (n=17) and v) late remission, no treatment (n=10). Other nephrotics, including those with focal glomerulosclerosis (FGS) were studied too and compared to normal subjects. Irrespective of underlying cause, untreated nephrotic subjects had significantly elevated plasma levels of fibrinogen, high molecular weight fibrin-fibrinogen complexes and fibrinogen first derivatives. α2 macroglobulin levels were elevated too whereas, factor XIII, α1-antitrypsin, plasminogen and, surprisingly, antithrombin III levels were not different from normal. Values reverted toward normal when MCNS patients began to respond to steroid treatment (group iii) and were normal in groups iv and v. Abnormalities persisted in FGS patients who remained nephrotic. Thus coagulation changes occur prior to the administration of steroids and appear to be nonspecific being found in nephrotic syndrome irrespective of etiology. Our study provides a rationale for the recently advocated longterm use of oral anticoagulants in FGS patients (J.Ped.Neph.,1980,1,18) to prevent development of glomerulosclerosis and chronic renal failure.