Search

Nephrotic syndrome frequently causes thromboembolic complications in veins. Arterial thrombosis, however, is relatively rare. We report the case of a 47-year-old male with nephrotic syndrome complicated with abdominal aortic thrombosis. The patient complained of pain in the bilateral lower extremities 2 weeks after the development of nephrotic syndrome. The aortogram revealed complete occlusion of the abdominal aorta just below the origin of the inferior mesenteric artery. Necrosis of the legs extended rapidly, and he eventually lost his legs. Among various predisposing factors, hypercoagulability associated with nephrotic syndrome seemed to be responsible for the development of thrombosis. Thrombotic complications are sometimes serious in the nephrotic patient. Assessment for the risk factors is required to warrant prophylactic anticoagulation.

A 63 year old man with central nervous system lupus with a neurogenic bladder and visual disturbance is described. The diagnosis of neurogenic bladder, attributed to peripheral neuropathy, was made on the basis of cystometrography and clinical symptoms. A brain magnetic resonance imaging scan showed gliosis along the cerebral vessels and the optic nerve. This case shows that systemic lupus erythematosus can be accompanied by a peripheral neurogenic bladder and visual disturbance, and that these symptoms may not improve despite the amelioration of other lupus symptoms on treatment with steroids.

The management and screening of unruptured asymptomatic intracranial aneurysm (ICA) in patients with ADPKD and those with a family history of ICA remains a subject of considerable controversy. In recent years, it has been revealed that MRA (magnetic resonance angiography) can define the circle of Willis to allow detection of ICA as small as 3-4 mm. We report a case of a 63-year-old man with ADPKD and his family. No definite aneurysm was observed by angiography screening at 46 years of age, when he was referred for hemodialysis. For the past three years, his family history revealed that three relatives were suffering from subarachnoid hemorrhage at the ages of 32, 36 and 39 years, respectively, two of whom had ICA and one had arterio-venous malformation detected by angiography. Whether they had ADPKD was unknown, but two were suggestive of ADPKD. Therefore, our case underwent MRA as screening for ICA, which showed an ICA with a diameter of 5mm in the anterior communicating artery. The ICA was confirmed as being 6 mm in diameter by conventional angiography. His niece and her son, who had ADPKD, also underwent MRA, which showed a suspicious image of a 2 mm ICA in the latter case. These results suggest that prophylactic screening for ICA is important in an ICA clustering family. MRA is useful in screening for ICA and in the follow-up study on the natural course of ICA.

It is not certain whether the life expectancy of patients with membranous nephropathy is shorter than that of an age-matched healthy population. Forty-one patients (21 males, 20 females) aged between 16 and 70 years (average age: 33.3 years) were followed for 20 years. The patients were divided into two groups: group I (n = 18), consisting of patients in whom nephrotic syndrome persisted for more than two years or until death, and group II (n = 23), consisting of patients except for group I. The non-survival criteria are death or renal death. Twelve patients (29.3%) died during the study period. Eight patients belonged to group I and 4 to group II. The causes of death in group I patients were end-stage renal failure in 3 cases, ischemic heart disease in 1 case, subarachnoid hemorrhage in 1 case, malignancy in 2 cases, suicide in 1 case, and those in the group II patients were pneumonia, malignancy, cerebral softening, and diabetes mellitus, respectively. Eight patients who died in group I had a significantly longer difference between their actual life span (ALS) and life expectancy (LE) and a significantly smaller ratio of ALS to LE than the patients who died in group II (ALS-LE: -29.9 +/- 4.5 years in group I vs. -9.0 +/- 6.8 years in group II, p0.05, ALS x 100/LE: 22.5 +/- 8.0% in group I vs. 80.9 +/- 25.2% in group II, p0.05). In group I, the ratio of observed to expected death was 4.76 (95% confidence interval, 2.05 to 9.37) and significantly higher than that of the control population. In group II, however, the ratio was 1.09 (95% confidence interval, 0.30 to 2.80), and the difference from the control population was not statistically significant. These results suggest that longstanding nephrotic syndrome is associated with a shortened life expectancy in patients with membranous nephropathy.

Risk factors for contrast nephropathy were prospectively studied in 17 patients with non-insulin dependent diabetes mellitus undergoing cardioangiography. Contrast nephropathy, defined as a serum creatinine increase of greater than 25% at 3 day after angiography, occurred in 29.4% of diabetic patients. Patients who developed contrast nephropathy had significantly higher serum creatinine (Cr), fractional excretion of sodium (FENa), urinary albumin excretion rate (AER), and lower 24hr Ccr than patients who did not (Cr: 1.5 +/- 0.3 mg/dl vs. 0.8 +/- 0.1 mg/dl, FENa: 1.9 +/- 0.5% vs. 0.6 +/- 0.1%, AER: 522 +/- 335 micrograms/min vs. 27 +/- 13 micrograms/min, 24hr Ccr: 39.1 +/- 11.6 ml/min vs. 86.2 +/- 9.3 ml/min, P0.05). Contrast nephropathy developed in all of two patients with overt proteinuria (AER more than 200 micrograms/min), but none of eight patients with normoalbuminuria (AER below 15 micrograms/min). Three of seven patients with microalbuminuria developed contrast nephropathy, and two of them had advanced nephropathy. FENa obtained next day was significantly elevated over baseline in patients with contrast nephropathy (1.9 +/- 0.5% vs. 9.7 +/- 4.5%, P0.05), but unchanged in patients without contrast nephropathy. The rise in C beta 2-microglobulin/Ccr and enzymuria was noted in both group. Percentage decrease of Ccr on the next day was positively correlated with FENa before angiography (r = 0.645, p0.01). Of 24hr Ccr, AER, and FENa before angiography, FENa was revealed as a statistically significant discriminant factor for contrast nephropathy by stepwise discriminant analysis (p = 0.0008). These results suggest that contrast nephropathy develops predominantly in the stage not of incipient but of overt diabetic nephropathy indicated by a decline of glomerular filtration, overt proteinuria, and tubular dysfunction. Of them, tubular dysfunction may be the most important risk factor for contrast nephropathy.

Interleukin-6 (IL-6) plays a key role in inflammatory and immune responses in the host. In the present study, the IL-6 activity in urine from patients with various renal diseases was examined to elucidate the pathological and clinical significance of urinary IL-6. In patients with mesangial proliferative glomerulonephritis (mes-PGN) including, IgA nephropathy, the urinary IL-6 activity tended to increase with the progression of mesangial hypercellularity. In four patients with IgA nephropathy, urinary IL-6 activity increased markedly but transiently during episodes of acute exacerbation associated with upper respiratory tract infection. In addition, it was demonstrated that urine from patients with other types of PGN such as poststreptococcal acute glomerulonephritis and membrano-proliferative glomerulonephritis contained large quantities of IL-6. However, the levels of urinary IL-6 activity were almost within the normal range in non-proliferative glomerular diseases such as membranous nephropathy, minimal change nephrotic syndrome and lupus nephritis (WHO class I and V), non-glomerular bleeding and orthostatic proteinuria. It should be noted that a marked increase in urinary IL-6 was often observed in the patients with urinary tract infection. These results indicated that IL-6 in urine might be derived from various types of cells participating in inflammatory reactions not only in the renal parenchyma but also in the urinary tract.

For a characterization of the clinical course of crescentic glomerulonephritis (Cres. GN), reciprocals of serum creatinine concentration (1/Cr) as a function of time were studied in 24 patients. The patients fulfilled the following criteria; 1) crescents were observed in more than 50% of glomeruli, and 2) the increment of serum creatinine could be determined sequentially on three or more occasions in the phase of progression of renal impairment. In all patients 1/Cr declined linearly with time with correlation coefficients between 0.881 and 0.993. According to the slope, the patients were divided into two groups; an acute group (13 patients) with slopes of -1.0 x 10(-2) dl/mg/day or more steep, i.e. with increments of serum creatinine from 1.0 to 10.0 mg/dl within 90 days, and a subacute group (11 patients) with less steep slopes. Histologically, there was no difference in the percentage of glomeruli with crescents between the two groups. However, in the acute group a negative correlation was found between the period from onset to histological examination and the percentage of glomeruli with cellular crescents in all glomeruli with various crescents (r = -0.872, p less than 0.001), while in the subacute group the percentage was nearly constant regardless of the time of histological examination. These mean drastic but transient activation of the disease in the former in spite of a persistence of indolent activity in the latter. Clinically, in the acute group an improvement of serum creatinine was observed in 8 (61.5%) vs. only 2 (18.2%) in the subacute group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

e16098 Background: We previously reported that mRNA of interferon-alpha receptor type 2 (IFNAR2) was upregulated in metastatic and IFN-a resistant renal cell carcinoma (RCC) in comparison to localized RCC or metastatic tumors with good response to IFN-a (BMC Cancer, 2007). We speculated potential different molecular mechanism between above two groups. Protein profiling using human tumor tissues may give insight into cellular pathways leading to carcinogenesis and metastasis in RCC. Methods: We examined mRNAs expression for IFNAR2 in paired tumor and non-tumor samples from the surgical specimens of Japanese patients with RCC using a real-time reverse transcription polymerase chain reaction. Then we selected representative five IFNAR2 upregulated clear cell carcinomas cases with metastatic tumor, five IFNAR2 upregulated metastatic sarcomatoid carcinomas, and five normal expression clear cell carcinomas with localized tumor. We investigated protein profiling in the tumor tissues of above three groups using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) coupled with IMAC-Cu chips. Results: For hierarchical clustering analysis, we used the 25 peaks which revealed significant differences in single-marker analysis in the range from 1,500 to 10,000 m/z. The heat map analysis based on the clustering distinguished completely metastatic tumors with IFNAR2 upregulated groups from localized tumors with IFNAR2 normal expression group. Furthermore, the heat map discriminated metastatic sarcomatoid carcinomas from metastatic clear cell carcinomas with a sensitivity of 100% and a specificity of 80%. Conclusions: SELDI-TOF MS profiling of tumor tissues can be applied to differentiate patients with three types of RCCs. Our findings may reflect different molecular mechanism between localized and metastatic carcinomas, and the different response to immunotherapy with IFN-α. This may shed light on the potential therapeutic strategy for IFN-α treatment. However, further investigation is required to verify the usefulness of this method in clinical practice. No significant financial relationships to disclose.

In an attempt to clarify the influence of pregnancy on the natural course of the chronic glomerulonephritis with impaired renal function (glomerular filtration rate: GFR less than or equal to 70 ml/min), the courses of 14 pregnancies occurring in 10 patients (seven with IgA nephropathy, one with membranoproliferative glomerulonephritis, one with membranous nephropathy and one with hereditary nephropathy) were studied. In 8 patients GFR measured before pregnancies ranged from 46 to 70 ml/min and in the other two creatinine clearance estimated in the first trimester of pregnancies was 62 and 49 ml/min, respectively. The pregnancies resulted in 10 live births, one spontaneous abortion, one artificial abortion and 2 neonatal deaths. In 2 out of 10 live births fetal weight was less than 2500 g. In 3 of 11 pregnancies there was neither increase in urinary protein nor elevation of blood pressure during pregnancies, while seven (64%) had increased proteinuria during the third trimester, and 4 of them were also complicated with hypertension. In 6 of 10 patients, there was no decrease in GFR during pregnancies. In three patients GFR was decreased from 70 to 36 ml/min, 70 to 58 ml/min and 62 to 48 ml/min, respectively. However, these reductions were considered to go with the natural course of respective patients because the reduction slopes were almost the same or rather mild in comparison with those estimated before or after pregnancies. The other patient also had a transient increase in serum creatinine level during two pregnancies, but the reciprocals of serum creatinine concentration before and after the pregnanciesdeclined linearly with time. These data suggest that pregnancy might have little influence on the natural course of the chronic glomerulonephritis even if complicated with renal functional impairment defined as GFR of 70 ml/min or less.

We report a case of Klinefelter's syndrome who developed a decrease of serum gonadotropin levels, particularly LH, after CyA treatment for complicated focal glomerulosclerosis (FGS). A 38-year-old man suffering from general malaise and pretibial edema was diagnosed FGS by renal biopsy in October 1988, and was referred to our hospital for further evaluation and treatment for FGS in December 1988. He was not married, and closer anamnesis revealed that he had had impaired seminal ejaculation from the age of 30. The physical examination showed 37% obesity, scanty body hair, pretibial edema and small bilateral testes (3.0 x 1.5cm). Laboratory findings included marked proteinuria (5.3g/day) and mild renal dysfunction (serum creatinine 1.3mg/dl, glomerular filtration rate 57.2ml/min). Endocrinologically, high basal levels of LH and FSH (133.6mIU/ml and 93.7mIU/ml, respectively) and the hyperresponses of LH and FSH to LH-RH stimulation were found, but the other pituitary hormone levels, thyroid and adrenal status, were in the normal range. In testicular biopsy, nodularly proliferated Leydig cells and no seminal tubules could be seen. The chromosome analysis showed 47,XXY karyotype, which confirmed the diagnosis of Klinefelter's syndrome in this patient. From 9 January 1989, CyA (6mg/Kg.day) was orally administered for 4 weeks in order to treat for FGS. After CyA administration, basal levels of LH and FSH remarkably decreased, particularly LH, and their decrease lasted for at least 6 weeks after cessation of CyA (final levels; LH 28.2mIU/ml, FSH 69.8mIU/ml). On the other hand, serum testosterone level was low normal or slightly under normal, and no apparent changes could be seen during CyA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

A 38-year-old Japanese man suffering from nephrotic syndrome and slowly progressive impairment of renal function underwent renal biopsy. Light microscopy revealed diffuse lobular accentuation of glomerular tufts, occupied by homogeneous material which was eosinophilic, lightly stained with periodic acid silver methenamine and deeply with aniline blue. Further examinations using an electron microscope after treatment with phosphotungstic acid revealed that this material exhibited a diffuse increase in fibers having a periodicity of 65 +/- 4 nm (mean +/- SD) like type III collagen fibers and was reactive to the anti-type III collagen monoclonal antibody. In addition, the serum level of procollagen III peptides was markedly elevated to 221 ng/dl (normal range 2-13 ng/dl). However, the fibers were peculiarly curved and frayed as reported in the nail-patella syndrome, but were not observed in the lamina densa of the glomerular basement membrane (GBM) as seen in this syndrome. No family history or physical findings of bony and nail dystrophy, no laboratory data or pathological findings compatible with already described renal diseases including mesangiocapillary glomerulonephritis, light chain disease, immunotactoid nephropathy, amyloidosis, and non-amyloidotic fibrillary glomerulonephritis were observed. These data strongly suggest that the nephropathy is caused by a primary increase in atypical type III collagen fibers in glomeruli (primary glomerular fibrosis), which to our knowledge has not yet been described in the English literature.

The proportion of B lymphocyte subsets with surface immunoglobulin G (sIgG) was significantly increased in minimal change nephrotic syndrome (MCNS), membranous nephropathy, IgA nephropathy and mesangiocapillary glomerulonephritis (MCGN) and with sIgA in IgA nephropathy and MCGN, and with sIgE in MCNS. Increased subsets in membranous nephropathy, IgA nephropathy and MCGN corresponded to the immunoglobulins deposited in the glomeruli, and the increased subset of sIgE in MCNS was correlated with the elevation of serum IgE. These results suggest that each disease studied has a characteristic subset pattern of B lymphocyte response. This may have an important role in determining the histological type of idiopathic glomerulonephritis.

To clarify long-term prognosis and risk factors of IgA nephropathy, 205 patients with the disease were followed up for a period of 1 to 22 years with a mean of 7.9 years. According to the percentage of glomeruli involved with extracapillary lesions (ECL), which were defined by crescents and fibrous adhesion of glomerular tufts to Bowman's capsule, the patients were divided into four groups: group 1-absence of ECL; group 2-less than 25%; group 3-25-50%; group 4-more than 50%. During the follow-up period, 26 patients progressed to chronic renal failure requiring hemodialysis, and one patient died of acute peritonitis. The actuarial kidney survival rate was 90.4% for 5 years and 86.0% for 10 years. Ten-year survival rates were 100% in group 1, 94.3% in group 2, 81.8% in group 3 and 25.5% in group 4. Re-biopsy specimens, observed in 31 patients after intervals of 1.4 to 13.4 years, revealed an increase of ECL in 20 patients concomitant with an apparent reduction of renal function in 13, whereas in the other 11 patients with no increase, renal function remained unchanged. These results strongly suggest that ECL plays an important role in the progression of IgA nephropathy, and renal function could be impaired by repeated formation and accumulation of these lesions.

Renal biopsy specimens of 16 patients with massive proteinuria, which developed during pregnancy and had lasted as late as one month after delivery, but disappeared within 15 months were studied. Four of them disclosed focal segmental hyalinosis, sclerosis, markedly swollen and foamy endocapillary cells, and ballooning of the involved tufts. Double contour of the capillary walls, predominance of epithelial cells as well as swelling of endocapillary cells known in pre-eclampsia were also observed. Electron and immunofluorescence microscopies revealed subendothelial deposition of IgM, C3 and rather weak fibrinogen-related antigens. These results indicate that focal glomerular sclerosis may develop during pre-eclamptic pregnancy, but may follow a non-progressive clinical course after delivery.

One hundred and four consecutive patients with idiopathic membranous nephropathy have been followed for 24 years. The actuarial survival rates in 5, 10 and 15 years were 94.6, 90.0 and 80.3%, respectively. Within the first 5 years clinical status improved gradually, but thereafter entered into an equilibrated state, when approximately 70% of the patients were in remission of absent (40%) or less than 1.0 g/24 hour urinary protein. As for renal function, within the initial 5 years around 80% of the patients revealed a glomerular filtration rate (GFR) greater than 80 ml/min. This percentage reduced approximately to 70 and 50% over periods of 10 and 15 years, whereas a mean reduction rate of GFR was only 15 ml/min over a period of 8 years. The clinical status at the 5th year correlated well with its outcome (rs = 0.676, p less than 0.001) and GFR estimated around the 5th year with the final estimate (r = 0.796, p less than 0.001). These data suggest that membranous nephropathy follows a fairly good clinical course, and that the 5th year clinical status and renal function are valuable prognostic indices of the disease.

Seventeen kidney specimens (6 biopsies and 11 autopsies) of Takayasu's arteritis disclosed two types of glomerular lesions. One was a mild axial mesangial proliferation associated with intramembranous and mesangial electron dense deposits consisting of IgG, IgM and C3 (axial type). The other was a centrolobular mesangial thickening associated with a hyaline deposition showing a mosaic pattern ("centrolobular mesangiopathy": centrolobular type). Mesangiolytic lesions, nodulous lesions, microaneurysms in glomeruli and extensive deposition of hyaline materials both in afferent and efferent arterioles were also observed. The former lesion was found in 4 patients with an active arteritis; and the latter was mainly observed in autopsy cases having a long-term clinical course. In the genesis of the axial type, immune complex deposition caused by the active aortitis may be involved, while the glomerular ischemia caused by the vascular lesions may be implicated in the development of the centrolobular type.

A patient experienced the concomitant onset of psoriasis vulgaris and mesangiocapillary glomerulonephritis (MCGN) with massive proteinuria. Laboratory examination revealed reduced glomerular filtration rate (GFR), elevated serum IgG, IgA and circulating immune complex (CIC) levels. Both diseases responded promptly to combined therapy with prednisolone, urokinase and plasma exchange. CIC and GFR were normalized with histological improvement. To our knowledge, this is the first case of glomerulonephritis, which can be related to psoriasis vulgaris through an immune mechanism.

Thirty-two adult patients with minimal change nephrotic syndrome (MCNS) were studied in order to clarify the characteristics of the immune system in MCNS and their relation to clinical activity. In the active phase (n = 17), serum immunoglobulin (Ig) M and E levels, B lymphocytes (surface Ig-positive cells) and their subsets, surface IgG, IgM and IgE positive cells; B gamma, B mu and B epsilon, were increased, whereas the serum IgG level and OKT3-reactive cells, peripheral T lymphocytes; T3, were decreased. In the remitted phase maintained by steroid therapy (n = 17), serum Igs and B lymphocyte subsets tended to return to normal levels concomitant with decreases in T3 and T4, and an increase in T8 in consequence of a marked decrease in T4/T8 (helper/suppressor) ratio. In stable remission continuing with no steroid therapy (n = 14), the above abnormalities returned to normal ranges, except for serum IgM which remained at a high level and re-elevated serum IgE. These results suggest that immunological abnormalities in MCNS are characterized by acceleration of the IgE and IgM producing systems and impaired maturation of the IgG producing system despite normal differentiation from the IgM producing to IgG producing system, possibly caused by T lymphocyte dysfunction.

Fourteen patients with acute interstitial nephritis have been followed for an average of 64 months. Initial renal failure estimated by a reciprocal of serum creatinine improved rapidly and linearly within 6 to 8 weeks ("early improvement"). A slow improvement of GFR followed within one year, showing a new base line level of renal function, which was assessed as normal in five patients and was reduced in seven patients. Two patients died of non-renal disease. Final GFR was closely correlated with a degree of "early improvement", ages at onset and severity of interstitial lesions. The results suggest, 1) these indices are of much value in predicting long-term prognosis and 2) a certain degree of permanent impairment of renal function is rather common in the disease.