The glomerular tip lesion: a steroid responsive nephrotic syndrome

The glomerular tip nephropathy is a cause of the nephrotic syndrome and has distinct pathological features. Glomerular tufts appear normal on light microscopy except for a segmental lesion invariably present in all glomeruli at the origin of the proximal tubule. Data on twenty adults whose renal biopsies demonstrated this lesion and who were followed for a mean of 7.4 years are analyzed. Eighteen patients were treated with steroids; ten of these had complete remission of proteinuria and seven a significant reduction of their proteinuria. Ten patients had moderately impaired renal function (serum creatinine greater than 120 mumol/l) at presentation, eight received steroids and achieved a reduction in serum creatinine. The prognosis was good, with no patient developing chronic renal failure requiring dialysis.     

Spontaneous remission of nephrotic syndrome in IgA glomerular disease

We report two cases of adult onset nephrotic syndrome with pathologic features of minimal change disease but a predominance of IgA in mesangial regions. Both cases underwent spontaneous remission despite an episode of recurrent nephrotic syndrome in one patient. The relationship of the glomerular disease to minimal change and IgA nephritis is discussed.     

Frequency of Mesangial IgA Deposits in a Non-Selected Autopsy Series

The frequency of mesangial IgA deposition was examined in 250consecutive autopsy cases without known renal disease. Diffusegranular mesangial deposits of IgA were detected in 12 of 250cases (4.8%). In six patients IgA deposits were associated withliver cirrhosis. Six patients (2.4%) suffered from various otherconditions including endocarditis, bronchial asthma, cardiovasculardisease, and neoplasia. Two of these patients had completelynegative urine analysis on repeated investigations, whereasthree patients exhibited microscopic haematuria and/or mildproteinuria. IgA₁ was the major constituent in all specimens.C3c deposits in glomeruli were detected in one kidney. Our findingsindicate that clinically overt renal disease is present in onlya limited proportion of individuals with mesangial IgA deposits.Apparently, it represents the tip of an iceberg.     

The clinical significance of mesangial IgM deposits and mesangial hypercellularity in minimal change nephrotic syndrome

Some patients with minimal change nephrotic syndrome (MCNS) present on biopsy mesangial IgM deposits, which may be associated with mesangial hyperplasia. These patients have been considered as a possible subset with a different response to therapy as well as prognosis and designated as mesangial IgM nephropathy or mesangial proliferative glomerulonephritis. However, the clinical relevance of these biopsy findings has been questioned by others. We reviewed the clinical, biopsy, and follow-up data in 61 MCNS children, 33 with mesangial IgM and 28 free of immunoglobulins. There were no significant differences in response to therapy or prognosis between these two groups. The lack of IgM elution and heterologous in vitro C3 fixation in the biopsies of some MCNS cases with IgM mesangial deposits does not support the possibility that the deposited IgM plays an immunologic role.     

Impaired solubilization of glomerular immune deposits by sera from patients with IgA nephropathy

A study of the solubilization of glomerular immune deposits by sera from patients with IgA nephropathy is described. Renal biopsy specimens were obtained from patients with IgA nephropathy and other glomerular diseases. These specimens were incubated with fresh and heated sera from the same patients and healthy adults at 37 degrees C for one hour in plastic tubes. The sections were stained with fluorescein isothiocyanate (FITC)-labeled heavy chain specific anti-human IgA antiserum and then examined with a fluorescent microscope. It was shown that the solubilization of glomerular immune deposits by sera from patients with IgA nephropathy was significantly less than that by sera from healthy adults. It is possible that impaired solubilization of immune complexes in vivo could lead to the accumulation of glomerular immune deposits in patients with IgA nephropathy.     

Spontaneous remission of nephrotic syndrome in a patient with IgA nephropathy

A patient with spontaneous remission of nephrotic syndrome (NS) associated with IgA nephropathy is described. The patient presented at the age of 8 years with asymptomatic proteinuria, and at the age of 11 years developed classical features of NS. A percutaneous renal biopsy showed mild mesangial prominence without significant hypercellularity, electron-dense deposits within the mesangium, and 3+mesangial staining with IgA and IgG. NS resolved 6 weeks after onset without any form of therapy; absence of protein-uria persisted 6 months later. This report demonstrates clearly that patients with NS associated with IgA nephropathy may undergo spontaneous resolution of their proteinuria.     

先天性微小病变型肾病综合征一例

息儿,男,2月大,因双下肢水肿20 d于2005年7月29日入本院.患儿系第2胎第2产,足月顺产,无窒息史,胎盘大小正常,出生体质量3.75 kg.于生后第50天无明显诱因下出现双下肢凹陷性水肿,曾在当地医院查尿蛋白为2+～3+.拟诊"先天性肾病综合征",予对症治疗,期间未用激素,效果不佳,遂转入我院诊治.家族史无特殊.查体:颜面无明显水肿,腹膨隆,移动性浊音阳性,阴囊明显水肿,双下肢凹陷性水肿.实验室检查:多次尿蛋白3+,血清白蛋白4.9 g/L,胆固醇7.23 mmol/L,TORCH、HIV-Ab、梅毒螺旋体抗体、乙肝五项均正常.     

Minimal change nephrotic syndrome with predominant mesangial IgA deposits: clinicopathological study

It has been reported that minimal change nephrotic syndrome (MCNS) shows no deposit of immunoglobulins or complement components in the glomeruli. We found 6 patients with IgA deposits in the glomeruli among 101 patients with MCNS, and examined the clinicopathological features of these cases. In all cases, light microscopy showed minor glomerular abnormalities. However, immunohistochemical study demonstrated marked IgA deposits in the glomerular mesangium. IgM was detected in 5 cases, IgG in 2, C3 in 2, and Clq in 1. On electron microscopy, small mesangial deposits were found in all cases and foot process effacement was partially demonstrated. There were no abnormalities in the glomerular basement membrane. The renal functions were within normal ranges in all 6 cases. In three cases, biopsies were performed within a month after the initiation of profuse proteinuria. In the other three cases, frequent relapses had been observed for 6 to 15 years before the biopsies. However, all patients ultimately revealed complete remission with corticosteroid treatment. Serum IgA levels were within normal range in examined 4 cases. Hematuria was negative in all of them. The clinical findings seem to be identical to MCNS rather than IgA nephropathy, and IgA deposits may have no pathogenetic significance, although the pattern of deposition looks quite similar to that of IgA nephropathy. These results indicate that the renal lesions in the 6 patients may belong to the subtype of MCNS, rather than IgA nephropathy.     

Thymoma associated with myasthenia gravis and minimal lesion nephrotic syndrome

A nephrotic syndrome has been observed rarely in association with thymoma. In most of the reported cases, it occurs when the thymoma is in remission; histological examination generally shows minimal change disease. We report a case of a 43-year-old man presenting with minimal lesion nephrotic syndrome at the time of the diagnosis of thymoma and myasthenia gravis, which persists despite remission of the thymoma. The role of a disorder of T-cell function and of circulating cytokines is discussed.     

Waldenstr?m macroglobulinemia and nephrotic syndrome with minimal change lesion

A case of Waldenstr?m macroglobulinemia with nephrotic syndrome is reported. Kidney biopsy, revealing only foot process fusion and response to steroid therapy, fits minimal change disease.     

IgA deficiency and membranous glomerulonephritis presenting as nephrotic syndrome

Selective IgA deficiency associated with glomerulonephritis is rare and no previous reports in childhood have been made of the association of IgA deficiency and membranous glomerulonephritis (MGN). We report a 5-year-old boy with selective IgA deficiency and MGN. He presented with nephrotic syndrome. Percutaneous renal needle biopsy showed diffuse global thickening on light microscopy and heavy IgG and moderate C3 deposits were found on immunofluorescence. Electron microscopy detected extensive global subepithelial deposition of electron-dense material with frequent intramembranous extension and spike formation. The pathological diagnosis was diffuse MGN stage 1. Oral prednisolone (1 mg kg^–1 day^–1), angiotensin-converting enzyme inhibitors (ACEI), and angiotensin II receptor blocker (ARB) were given resulting in reduction of proteinuria. The prednisolone dose was gradually tapered and discontinued after 2 months. At present the patient has been in complete remission for 10 months despite the discontinuance of prednisolone. In conclusion, our treatment with corticosteroid, ACEI and ARB reduced proteinuria and was effective for our case with selective IgA deficiency and MGN.     

Mesangial immunoglobulin A deposits in minimal change nephrotic syndrome: a report of an older patient and review of the literature

A 57-year-old patient with a history of monoclonal immunoglobulin A (IgA) gammopathy developed idiopathic nephrotic syndrome. Renal biopsy showed minimal glomerular changes with predominant glomerular mesangial IgA. The association of glomerular mesangial IgA with otherwise typical minimal change nephrotic syndrome has been noted before, and the literature concerning this combination of findings is reviewed. The patient herein described represents one of the two oldest patients yet reported with this syndrome and raises questions about the relationship between minimal change disease and IgA nephropathy. Severe proteinuria (and even the nephrotic syndrome) is not necessarily the harbinger of a poor prognosis in IgA nephropathy if the glomerular morphology is otherwise consistent with minimal change nephrotic syndrome. Such patients should be treated in a fashion similar to those with minimal change nephrotic syndrome. The significance of the IgA gammopathy in the pathogenesis of this case is unknown.     

Impact of mesangial IgA deposits in 14th-postoperative-day routine renal allograft biopsies

SUMMARY: Three hundred fourteen 14th-postoperative-day routine renal allograft biopsies were evaluated together with clinical data. Out of 314 biopsies, mesangial IgA deposits were positive in 122 biopsies (39%). According to Banff classification, the rate of acute rejection was significantly lower in mesangial IgA deposit-positive (IgA(+)) patients (7.4%) than in mesangial IgA deposit-negative (IgA(-)) patients (19.7%) on the 14th postoperative day. Thereafter, rate of biopsy-proven and clinical acute rejection was continuously lower for up to 12 months in IgA(+) patients than in IgA(-) patients. the detection rate of mesangial IgA deposits was significantly higher in human leucocyte antigen (HLA)-well-matched (HLA mismatch number was <3) patients than in HLA-poorly matched (HLA mismatch number was <3) patients. In HLA-well-matched patients, the serum creatinine levels were significantly lower in IgA(+) patients than in IgA(-) patients after 3 post-transplant months and up to 1 post-transplant year. Follow-up (mean interval: 13 months) allograft biopsies were performed in 34 patients out of 122 IgA(+) patients. In the follow-up biopsies, initially detected mesangial IgA deposits had disappeared in 22 patients (65%) out of 34 patients. Twelve patients (35%) still had mesangial IgA deposits, and all of them had clinical and pathological findings consistent with IgA nephropathy. Patients with continuous mesangial IgA deposits in the follow-up biopsies had a better renal function at 1 year and a higher 5-year graft survival rate compared with patients who lost the initially deposited IgA. the present study demonstrates that long-lasting mesangial IgA deposits in renal transplants prevent allografts from acute rejection, which leads to better graft outcome.     

Clinico-pathological evaluation of mesangial IgA deposition of minimal change with nephrotic syndrome

The case of IgA glomerulonephritis that shows minimal change with nephrotic syndrome is unusual. Thirteen patients of mesangial IgA deposition of minimal change with nephrotic syndrome (IgAMCNS) are discussed in comparison with twenty patients of non IgA deposition of minimal change with nephrotic syndrome (MCNS). On a common basis of hematuria, two groups are undistinguished. On a reaction pattern to steroid treatment, the former is based on IgA nephritis and the latter is based on minimal change with nephrotic syndrome. There is no difference in light microscopical findings between the two groups. Electron microscopically, the former suggests IgA nephritis and the latter suggests minimal change with nephrotic syndrome. In immunofluorescence, the former group is rare to show typical IgA glomerulonephritis. In conclusion, IgAMCNS is considered to be nephrotic syndrome with asymptomatic IgA deposit in mesangium.     

Circulating mediators of proteinuria in idiopathic minimal lesion nephrotic syndrome

The pathogenesis of proteinuria in idiopathic minimal lesion nephrotic syndrome (IMLNS) remains to be elucidated. The most-accepted hypothesis is that the increased glomerular permeability to plasma proteins results from the effect of circulating factors on glomerular capillaries. This report critically reviews the current studies that have attempted to isolate and characterize this putative factor(s). Products released from hepatocyte or peripheral blood mononuclear cells or isolated by chromatography from serum or plasma have been tested in rats for their role in inducing proteinuria. These factors have been infused into the isolated kidney preparation or into the intact animal as a single venous injection, or continuously by pump for a period of 4 h to 7 days. Several of these isolated factors have been shown to induce proteinuria in rats. However, their exclusive pathogenetic role is questionable since none is always present in all IMLNS patients during relapse. Therefore, the increase in proteinuria in these patients may result from a single or a variety of factors as yet to be identified. Received: 1 September 1999 / Revised: 4 November 1999 / Accepted: 4 November 1999