Expression pattern of Galectin 4 in rat placentation.

Galectin 4 (Gal4) is abundantly expressed in the epithelium of the gastrointestinal tract, and functional analysis has concentrated on its roles associated with polarized membrane trafficking. This study aimed to investigate the expression of Gal4 in placentation. The expression level of Gal4 was revealed to be lower in differentiated Rcho-1 cells (a model system of rat trophoblast differentiation) than in proliferative cells. In the rat placenta, immunohistochemical analysis showed that Gal4 is preferentially located in the maternal-fetal junctional zone. These results suggest that down-regulation of Gal4 may be involved in the promotion of trophoblast cell differentiation.

Twenty-year follow-up of acquired renal cystic disease.

AIMS: Since 1979 the diseased kidneys of 96 patients on replacement therapy with chronic renal failure due to chronic glomerulonephritis have been followed to investigate the development of acquired cysts and tumors. This is a report of the 20-year follow-up. MATERIALS AND METHODS: Ninety-six patients were followed using periodic CT scan and were divided into hemodialysis, renal transplantation, bilateral nephrectomy and deceased groups during the follow-up. In the hemodialysis group, 36 patients (19 males, 17 females) were followed for 20 years. RESULTS: Kidney volumes which were 57.8 (1.51) (geometric mean (geometric SD)) ml at start of the follow-up had become 185.3 (2.03) ml 20 years later in males, and in females, 57.3 (1.64) ml had become 99.7 (2.36) ml. The increased rate was 3.2 (2.06) fold in males and 1.7 (2.57) fold in females. This enlargement of the kidneys was due to acquired cysts. Kidney volumes at the 20-year follow-up had increased more significantly than those at the 15-year follow-up in males; however, kidney volumes at the 20-year follow-up had not changed in females, if compared with data at the 15-year follow-up. Kidney volumes in males at 20-year follow-up were significantly larger than those in females (p = 0.0232). Males with more than 3.2-fold in kidney volume increase at the 20-year follow-up were under the age of 40 at entry into this study (p = 0.0055), although the correlation between the degree of kidney volume increase and age was not significant (p = 0.0910). Kidney volumes in the transplantation group remained small. There was no new renal cell carcinoma development after 15-year follow-up except for the local recurrence of a previous operated case. Although 7 of 44 patients died during the past 20 years due to malignancy, no patient died of renal cell carcinoma because of early detection and treatment. One patient died of retroperitoneal bleeding, which is a complication of acquired renal cystic disease. CONCLUSION: Male preponderance of acquired cysts was maintained at the 20-year follow-up. There was a tendency for the rate of increase in acquired renal cystic disease to be larger in young males. No one died of renal cell carcinoma, although the incidence of renal cell carcinoma was high.

[Thrombosis of the abdominal aorta in a patient with nephrotic syndrome].

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.

Involvement of p38 mitogen-activated protein kinase followed by chemokine expression in crescentic glomerulonephritis.

p38 Mitogen-activated protein kinase (MAPK) is involved in the production and signal transduction of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha, and chemokines in vitro. However, the crucial role of p38 MAPK in the inflammatory processes of crescentic glomerulonephritis in vivo remains to be investigated. We showed a dramatic decrease in IL-1beta-induced phosphorylation of p38 MAPK, not extracellular signal-regulated kinases 1/2 or jun NH2-terminal kinase, in rat cultured mesangial cells by FR167653. We explored the effects of FR167653 as a specific inhibitor of p38 MAPK on renal injury and subsequent renal expression of chemokines in a progressive experimental crescentic glomerulonephritis model in Wistar-Kyoto rats. Rats developed crescentic glomerulonephritis leading to glomerulosclerosis and interstitial fibrosis by 56 days after the administration of nephrotoxic sera. The number of phosphorylated p38 MAPK-positive cells, detected mainly in crescents, correlated well with the percentage of crescents and number of ED-1-positive cells. Phosphorylated p38 MAPK-positive cells were downregulated in glomeruli in rats with the daily subcutaneous administration of FR167653 for 6 days. Concomitantly, renal expression of macrophage inflammatory protein-1alpha and monocyte chemoattractant protein-1/monocyte chemotactic and activating factor was markedly reduced by day 6. The severity of glomerulosclerosis and interstitial fibrosis significantly decreased by day 56, and renal function was preserved. These results suggest that p38 MAPK phosphorylation is pivotal for crescentic glomerulonephritis, followed by the subsequent expression of renal chemokines. This study provides evidence that regulation of p38 MAPK is a novel appealing therapeutic target for crescentic glomerulonephritis.

Acute glomerulonephritis after human parvovirus B19 infection.

We evaluated clinical and histological characteristics of four adult patients who presented with acute glomerulonephritic syndrome with serological confirmation of recent HPB19 infection. All patients had generalized edema with urinary abnormalities. Body weight gain ranged from 3 to 10 kg. Three of the patients had contact with erythema infectiosum simultaneously with or within 10 days before development of flu-like symptoms. Two patients had an erythematous rash, and one patient had lower-extremity purpura. Joint pain was present in three of the patients. All patients had proteinuria and hematuria. Renal functions were normal except in one patient who had a serum creatinine of 3.2 mg/dL. Three of the patients had hypocomplementemia. All renal biopsy specimens were characterized by glomerular leukocyte infiltration and endothelial cell swelling. Mesangiolysis was seen in three of the patients. C3 was deposited in a coarse granular pattern along the capillary walls in all cases. Electron microscopic examination showed marked expansion of the subendothelial space of glomerular capillaries in all patients. Subendothelial electron-dense deposits were present in all patients. Immunohistochemical analysis using monoclonal anti-HPB19 antibody showed that one of the four patients had positive staining in the glomeruli. DNA extracted from renal biopsy specimens contained HPB19 DNA, as shown by polymerase chain reaction (PCR) analysis in all patients. PCR amplification of the renal DNA generated a 104-bp product, which hybridized to an HPB19-specific probe. No control group subjects contained HPB19 DNA as determined by PCR. This circumstantial evidence indicates that HPB19 infection may be one of the causes of acute glomerulonephritis in normal individuals.

Hemolytic uremic syndrome associated with influenza A virus infection in an adult renal allograft recipient: case report and review of the literature.

Hemolytic uremic syndrome (HUS) is a rare but serious complication following renal transplantation. It usually develops early after transplantation, and ciclosporin treatment is the most common triggering factor. We report the case of a 35-year-old male with posttransplant HUS which developed 1 year after renal transplantation. He became febrile 4 days before the onset of HUS, and the significant rise in viral titer confirmed the diagnosis of influenza A virus infection. The association of ciclosporin treatment with HUS was unlikely, because of the late onset of HUS and the low ciclosporin trough levels. The patient was treated successfully without a dose reduction of ciclosporin. An etiologic relationship between influenza A virus and HUS was highly probable in our patient. We also review a total of 156 adult cases with HUS after renal transplantation described in the literature. The prognosis of posttransplant HUS differs according to the cause. The advent of ciclosporin has improved the graft survival rate and mortality of patients with rejection-induced HUS.

Digital glomerular reconstruction in a patient with a sporadic adult form of glomerulocystic kidney disease.

This study describes a sporadic adult form of glomerulocystic kidney disease in a 52-year-old man. To determine whether the aperture of the proximal tubule was stenosed or obstructed to clarify the pathogenesis of glomerular cyst development, 100 serial sections of the open biopsy specimen were made. Ten glomerular cysts were reconstructed using three-dimensional imaging analysis. Bowman's capsule (glomerular cyst) volume, the volume of glomerular tufts, and the area of the proximal tubular opening were estimated using imaging analysis. The volumes of Bowman's capsule and of glomerular tufts were 0.0098 +/- 0.0039 mm3 (mean +/- SD) (normal: 0.0041 to 0.0083 mm3) and 0.0026 +/- 0.0013 mm3, respectively. The area of the proximal tubular opening was 0.0017 +/- 0.0003 mm2 (normal: 0.0012 to 0.0028 mm2). There was neither obstruction nor stenosis of the opening of the renal tubule in this sporadic adult form of glomerulocystic kidney disease. After 4 years of hemodialysis, the glomerular cysts, as well as the kidneys, enlarged. This study shows that the main cause of glomerular cyst development is not glomerulotubular neck obstruction.

Fifteen-year follow-up of acquired renal cystic disease - a gender difference.

In 1979, 96 patients who had undergone hemodialysis for a mean of 3 years and 4 months were entered into this study. This follow-up study revealed that the bilateral kidney volume significantly increased over 10 years in 33 male patients. Kidneys were found to have enlarged 2.7 times over the 10-year follow-up period. However, in 24 females kidney volume did not change over 10 years. This paper reports further results in 39 dialysis patients (21 males and 18 females) who were followed from the 10th to 15th year. In male patients, mean volume was 196 +/- 218 ml (mean +/- SD) at the 10th year and had significantly increased to 225 +/- 213 ml at the 15th year (p < 0.02). In female patients, mean kidney volume was 78 +/- 51 ml at the 10th year and had increased to 117 +/- 91 ml at the 15th year (p < 0.01). The enlargement in kidney volume during the recent 5 years was 1.26 +/- 0.39-fold in males and 1.43 +/- 0.45-fold in females. These rates did not significantly differ between males and females. During this recent 5-year period, there were no surgical cases due to renal cell carcinoma. Therefore, over the entire patient-time dialysis period, there were 6 renal cell carcinomas in 1,470 patient years. In conclusion, 10- to 15-year follow-up studies of kidney size revealed that the enlargement in the kidney due to acquired cysts persisted in male patients, but the rate of increase slowed after 13.0 years of hemodialysis, while the enlargement in the kidney in female patients became significant at 17.7 years of hemodialysis, revealing the slowly progressive nature of acquired cysts in women.

Rapidly progressive glomerulonephritis concomitant with diabetic nephropathy.

We describe a rare case of a rapidly progressive glomerulonephritis (RPGN) superimposed on diabetic nephropathy. A 68-year-old woman with non-insulin-dependent diabetes mellitus (NIDDM) complicated with diabetic triopathy demonstrated a rapid deterioration of renal function. Her urinary sediment contained many red blood cell (RBC) cells and casts, suggesting an additional renal disease accompanying diabetic nephropathy. Renal biopsy revealed crescent formation in many glomeruli characteristic of the pauci-immune type of RPGN. Steroid pulse therapy transiently halted the deterioration in renal function, but the patient died of pneumonia complicated with methicillin-resistant staphylococcus aureus (MRSA) infection. The unusual findings in diabetic nephropathy indicated the coexistence of primary glomerulonephritis and diabetic glomerulosclerosis in this case.

High incidence of common bile duct dilatation in autosomal dominant polycystic kidney disease patients.

Two autosomal dominant kidney disease (ADPKD) patients with cholecystitis or communicating extrahepatic dilatation of the common bile duct accompanied by tiny common bile duct stones prompted us to examine the incidence of gall stone disease and dilatation of the common bile duct in ADPKD patients. Computed tomography scans were examined retrospectively in 55 ADPKD patients and 55 age-, gender-, and duration of dialysis-matched non-ADPKD patients. The incidence of calcium-containing gall stones found on tomography scans was the same: eight of the 55 ADPKD patients and nine of the 55 non-ADPKD patients. However, common bile duct dilatation, defined as measuring more than 7 mm in diameter at the pancreatic head on CT scans, was found more frequently in the ADPKD patients (22 patients; 40.0%) than in the non-ADPKD patients (5 patients; 9.1%) (P = 0.0002). These results suggest that the high incidence of intrapancreatic common bile duct dilatation in ADPKD is a previously undescribed sign of extracellular matrix remodeling in ADPKD.

[A familial case of ADPKD with intracranial aneurysms detected by MR angiography].

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.

Risk factors for infection and immunoglobulin replacement therapy in adult nephrotic syndrome.

Infection has been recognized as an important cause of morbidity and mortality in children with nephrotic syndrome. However, the incidence and severity of infection and the mechanisms responsible for the increased susceptibility to infection are still unclear in adults. We studied 86 consecutive adult patients with nephrotic syndrome but no diabetic nephropathy. Risk factors for infection were evaluated by logistic regression analysis. Infections were found in 16 patients (19%), of whom six died of infection and two developed end-stage renal failure associated with infection. The relative risk for bacterial infection among patients with serum immunoglobulin G (IgG) levels below 600 mg/dL was 6.74 compared with that for patients with serum IgG levels over 600 mg/dL (95% confidence interval, 1.22 to 36.32; P = 0.029). In patients with serum creatinine levels over 2.0 mg/dL, the relative risk of bacterial infection was 5.31 compared with patients with serum creatinine levels below 2.0 mg/dL (95% confidence interval, 1.08 to 26.09; P = 0.040). Intravenous immunoglobulin (10 to 15 g) was administered prospectively every 4 weeks to 18 patients with serum IgG levels below 600 mg/dL until serum IgG levels increased to over 600 mg/dL. Administration of immunoglobulin resulted in a decreased rate of bacterial infections to a level equal to that in patients with endogenous levels over 600 mg/dL. These data indicate that hypogammaglobulinemia and renal insufficiency are independent risk factors for bacterial infection in adult patients with nephrotic syndrome. The effects of intravenous immunoglobulin suggest that maintenance of serum IgG levels over 600 mg/dL may reduce the risk of infection.

Prevention of proteinuria by the administration of anti-interleukin 8 antibody in experimental acute immune complex-induced glomerulonephritis.

Glomerular infiltration by neutrophils is a hallmark of acute glomerulonephritis. The pathophysiological role of interleukin 8 (IL-8), a potent neutrophil chemotactic cytokine (chemokine), was explored in an animal model of acute immune complex-mediated glomerulonephritis by administering a neutralizing antibody against IL-8. Repeated injection of bovine serum albumin (BSA) into rabbits caused the deposition of immune complexes consisting of BSA and rabbit IgG in glomeruli. Histological analyses revealed a small but significant number of neutrophils in glomeruli and the fusion of epithelial cell foot processes. Concomitantly, urinary levels of protein and albumin increased markedly (3.20 +/- 0.97 and 1.39 +/- 0.53 mg/h, respectively) compared with those of untreated animals (0.77 +/- 0.21 and 0.01 +/- 0.01 mg/h, respectively). Anti-IL-8 antibody treatment decreased the number of neutrophils in glomeruli by 40% and dramatically prevented the fusion of epithelial cell foot process. Furthermore, treatment with anti-IL-8 antibody completely normalized the urinary levels of protein and albumin (0.89 +/- 0.15 and 0.02 +/- 0.01 mg/h, respectively). These results indicated that IL-8 participated in the impairment of renal functions in experimental acute immune complex-mediated glomerulonephritis through activating as well as recruiting neutrophils.

Detection of urinary interleukin-8 in glomerular diseases.

To clarify the mechanism of neutrophil infiltration in glomerulonephritis, both urinary and plasma levels of a potent neutrophil chemotactic cytokine, interleukin-8 (IL-8), were measured in 40 healthy volunteers and 96 patients with various renal diseases. The plasma IL-8 levels were less than 16 pg/ml. The urinary IL-8 levels were elevated in several renal diseases including IgA nephropathy (17 of 43), acute glomerulonephritis (4 of 6), lupus nephritis (11 of 15), purpura nephritis (2 of 4), membranoproliferative glomerulonephritis (1 of 1), and cryoglobulinemia (2 of 2). IL-8 was detected immunohistochemically in diseased glomeruli, suggesting its local production. Elevated urinary IL-8 levels during the acute phase or exacerbations were found to be decreased during spontaneous or steroid pulse therapy-induced convalescence in all patients examined. The urinary IL-8 levels were higher in patients with glomerular leukocyte infiltration than in those without infiltration. Collectively, local production of IL-8 in diseased glomeruli might be involved in the pathogenesis of the glomerular diseases and measurement of IL-8 in the urine might be useful for monitoring the glomerular diseases.

[Shortening of life expectancy in patients with membranous nephropathy--based on 20 years follow up study].

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, p < 0.05, ALS x 100/LE: 22.5 +/- 8.0% in group I vs. 80.9 +/- 25.2% in group II, p < 0.05). 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 in diabetic patients undergoing cardioangiography].

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, P < 0.05). 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%, P < 0.05), 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, p < 0.01). 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.