Fibronectin glomerulopathy complicated with persistent cloaca and congenital esophageal atresia: a case report and literature review.

BACKGROUND: Fibronectin glomerulopathy is a rare, inherited, autosomal dominant, glomerular disease characterized by proteinuria, microscopic hematuria, hypertension, massive glomerular deposits of fibronectin, and slow progression to end-stage renal failure. Because the incident of fibronectin glomerulopathy is extremely low, the pathophysiology, genetic abnormalities, epidemiology, and mechanisms remain to be elucidated. CASE PRESENTATION: We report a 21-year-old woman with fibronectin glomerulopathy, who had been diagnosed with persistent cloaca and congenital esophageal atresia at birth. She developed proteinuria and hematuria 7 months before admission. Urinary protein and serum creatinine levels were 3.38 g/gCr and 0.73 mg/dL. Renal biopsy showed severe mesangial widening due to massive deposits, which was positive periodic acid-Schiff and negative methenamine silver. Immunostaining was negative for immunoglobulin but positive for fibronectin. Electron microscopy showed diffuse mesangial granular deposits. Thus she was diagnosed with fibronectin glomerulopathy, despite a negative family history of kidney disease and lack of any known missense mutations of fibronectin 1 gene. CONCLUSION: We report a patient who developed fibronectin glomerulopathy during the clinical course of extremely rare congenital malformations, including persistent cloaca and congenital esophageal atresia. We describe a case of this condition in detail and summarize the 75 case reports of fibronectin glomerulopathy.

Heterochronic spontaneous rupture of bilateral renal cell carcinomas in a hemodialysis patient.

A 64-year-old man undergoing chronic hemodialysis was admitted under a shock state with macrohematuria and fatigue lasting for two hours. A blood analysis revealed severe anemia. Computed tomography disclosed a large right-sided perirenal hematoma. The patient was successfully treated with radical nephrectomy, leading to a histological diagnosis of spontaneous rupture of renal cell carcinoma (RCC). One year after rupture of the right RCC, he again developed macrohematuria and computed tomography revealed a left-sided perirenal hematoma. Radical nephrectomy followed by a histological examination revealed spontaneous rupture of the left-sided RCC. This case emphasizes the importance of conducting periodic imaging evaluations of chronic hemodialysis patients with renal cystic masses.

Diabetes influences peritoneal morphology in uremic patients at the initiation of peritoneal dialysis.

BACKGROUND: The peritoneum begins to undergo morphologic changes before the start of peritoneal dialysis (PD), particularly in diabetic patients. The present study was conducted to investigate the effects of diabetes on the peritoneum. METHODS: This study involved 17 patients who began receiving PD and had diabetes as an underlying disease (DM group), and 30 patients without diabetes who served as a control group (nonDM group). At the start of PD, the parietal peritoneum was sampled to assess submesothelial connective tissue thickness, number of capillaries and postcapillary venules, and indications of vasculopathy (grades 0 - 3). RESULTS: Submesothelial connective tissue thickness was significantly greater in the DM group than in the nonDM group (p < 0.01). The number of capillaries was significantly greater in the DM group (p < 0.01). Based on multivariate linear regression analysis, diabetes was identified as a significant independent variable of both submesothelial connective tissue thickness and number of capillaries (p < 0.01). CONCLUSIONS: In diabetic patients, morphologic changes of the peritoneum are marked at the start of PD.

Pseudorenal failure due to intraperitoneal bladder rupture after blunt trauma: usefulness of examining ascitic fluid sediment.

A 42-year-old man noted decreased urine output and visited our emergency department. He said that 3 days previously, he had gotten drunk and fallen down a set of stairs. Blood tests and abdominal contrast-enhanced computed tomography revealed no abnormalities. A serum creatinine level of 5.89 mg/dL led to a diagnosis of acute renal failure and his hospitalization. After admission, his ascitic fluid level gradually increased, suggesting urine leakage into the peritoneal cavity. Microscopic examination of his ascitic fluid sediment revealed the presence of hyaline casts enclosing renal tubular epithelial cells. Cystography demonstrated contrast medium leakage into the peritoneal cavity, which led to a diagnosis of bladder rupture. Examination of ascitic fluid sediment is simple and very useful for diagnosing bladder rupture.

Spironolactone inhibits hyperglycemia-induced podocyte injury by attenuating ROS production.

BACKGROUND: Accumulating evidence suggests that mineralocorticoid receptor (MR) blockade effectively reduces proteinuria in diabetic nephropathy although the renin-angiotensin-aldosterone system is generally suppressed in diabetes. The present study was designed to confirm the antiproteinuric effect of MR blockade in diabetic rats and elucidate its mechanism. METHODS: The present study investigated whether MR blockade inhibits hyperglycemia-induced podocyte injury, focusing on the involvement of reactive oxygen species (ROS) production, in diabetic rats and cultured podocytes. Sprague-Dawley rats were divided into three groups: control, streptozotocin (STZ; 75 mg/kg)-injected diabetic and STZ treated with spironolactone (SPL; 50 mg/kg/day) and sacrificed after 8, 16 and 24 weeks. RESULTS: Rats gradually developed proteinuria from 8 weeks after induction of diabetes. Immunostaining for Wilms' tumor-1 (WT1) and synaptopodin, markers of podocytes, was attenuated, whereas immunostaining for desmin, a marker of podocyte damage, and 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress, was up-regulated in the glomeruli of diabetic rats. Diabetic rats showed hypoaldosteronemia compared to the control, whereas SPL decreased proteinuria, ROS production and podocyte damage. To elucidate the paradox between hypoaldosteronemia and effect of SPL under hyperglycemia, the role of high glucose in MR activation and podocyte injury was explored. In cultured MR-expressing podocytes, high glucose significantly enhanced Sgk1 expression, activated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and ROS production and induced podocyte apoptosis. All these effects were inhibited by SPL. CONCLUSION: We conclude that hyperglycemia in diabetes, independent of plasma aldosterone concentration, induces podocyte injury through MR-mediated ROS production and leads to proteinuria. SPL inhibits hyperglycemia-induced podocyte injury by attenuating ROS production.

Successful initiation and maintenance of hemodialysis in an adult patient with complete transposition of the great arteries.

Cyanotic congenital heart disease (CCHD) is a life-threatening cardiac defect that requires palliative or corrective surgery in early life. Major advances in medical and surgical management have resulted in the survival of CCHD patients to adulthood with or without corrective surgery, though some are at risk of development of end-stage renal disease (ESRD) due to cyanotic nephropathy (CN). There is little or no information on the initiation and maintenance of hemodialysis (HD) in such patients. We present here a case of a 44-year-old man with complete transposition of the great arteries and CN-related ESRD. He had only received a bi-directional Glenn's operation and still suffered persistent severe hypoxemia and impaired cardiac function. ESRD was successfully treated with HD over more than 4 years. The case emphasizes the need for special attention in the selection and initiation of renal replacement therapy.

Involvement of p53-transactivated Puma in cisplatin-induced renal tubular cell death.

AIMS: The tumor suppressor protein p53 plays a critical role as a determinant of cell survival when cells are exposed to various toxic stresses, by preventing growth arrest, replication of damaged DNA, and apoptosis. A novel p53-dependent proapoptotic gene, Puma (p53 upregulated modulator of apoptosis) is thought to participate in this process. Recently, p53 was reported to play an essential role in cisplatin-induced renal tubular cell (RTC) death. The objective of the present study was to elucidate the roles of p53 and Puma in cisplatin-induced RTC death. MAIN METHODS: We examined the in vivo expression of p53 and Puma-alpha in the kidney and evaluated the modification of Puma-alpha expression and RTC death by in vitro treatment with pifithrin-alpha (PFT-alpha), a specific p53 inhibitor, or Puma-alpha-specific small interfering RNA (siRNA). KEY FINDINGS: While no immunoreactivity for anti-p53- and anti-Puma-alpha antibody was detected in the control rat kidney, de novo expression of p53 and Puma-alpha was identified in the proximal tubular cells of the outer medulla at 6 h after cisplatin injection. Upregulation of these proteins preceded severe RTC injury. In vitro experiments revealed that PFT-alpha inhibited upregulation of Puma-alpha, and inhibition of Puma-alpha, either by PFT-alpha or by Puma-alpha-specific siRNA, decreased RTC death induced by 24-h cisplatin exposure. SIGNIFICANCE: Our results indicated that p53 activation mediated cisplatin-induced RTC death through upregulation of Puma, and suggested that inhibition of p53 and Puma is beneficial for the prevention and treatment of cisplatin-induced acute renal failure.

A case report of syndrome of inappropriate secretion of antidiuretic hormone with marked edema due to administration of hypertonic saline.

A 61-year-old man had hyponatremia (serum Na 112 mmol/L), which was associated with disturbance of consciousness. Therefore, administration of hypertonic saline was commenced. Eventually he was diagnosed with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Hypertonic saline was continued for 45 days, and plasma Na concentration rose to 138 mmol/L. At that time we were consulted regarding further administration of hypertonic saline. At the time of the consultation marked edema had developed affecting the whole body. The cardiothoracic ratio was increased and pleural effusion was evident on the chest X-ray. Administration of hypertonic saline was discontinued to prevent further worsening of the edema. Furthermore, water restriction (500 mL/day) was started. Body weight decreased by 4.3 kg in 7 days and the edema was diminished. However, plasma Na concentration decreased to 117 mmol/L. At that stage, we needed to balance the treatment of hyponatremia to the increased extracellular fluid volume (ECF). To normalize the ECF, we carried out ultrafiltration (UF) three times. Resolution of edema by using an extracorporeal UF method allowed the control of plasma Na concentration. In this case increased ECF volume hindered the adjustment of plasma Na concentration. The infusion of hypertonic saline is now used commonly by physicians. It is necessary to consider the potential risks of such treatment.

Expression of synaptopodin and GLEPP1 as markers of steroid responsiveness in primary focal segmental glomerulosclerosis.

The crucial involvement of podocyte failure in the development of hereditary focal segmental glomerulosclerosis (FSGS) indicates that specific podocyte proteins are closely related to podocyte function and biology. We hypothesized that podocyte failure, reflected by alteration of these proteins, leads not only to FSGS but also to resistance to steroid therapy. We investigated the association between expression of synaptopodin and glomerular epithelial protein 1 (GLEPP1) and response to corticosteroid therapy in primary FSGS. The subjects of this retrospective study were 17 adult patients with primary FSGS with nephrotic syndrome (NS) seen at Fukuoka Red Cross Hospital between 1979 and 2001. They were divided into two groups according to the response to steroid therapy at 6months: responders (n=10) and non-responders (persistence of nephrotic-range proteinuria, n=7). Expression levels of synaptopodin and GLEPP1 were examined immunohistochemically using image analysis software. Low expression levels of both proteins were associated with poor steroid responsiveness in FSGS. The average gray values for synaptopodin and GLEPP1 expression in responders vs. non-responders were 9.0+/-0.7 (mean+/-S.E.M.) vs. 6.3+/-0.9 (P=0.04) and 9.6+/-1.2 vs. 6.0+/-1.0 (P=0.04), respectively. The percentages of glomerular area staining for synaptopodin and GLEPP1 in responders vs. non-responders were 15.4+/-2.7% vs. 8.1+/-1.2% (P=0.045) and 11.9+/-1.6% vs. 6.0+/-1.3% (P=0.02), respectively. Synaptopodin expression correlated with the severity of proteinuria and with GLEPP1 expression. Reduced expression of both synaptopodin and GLEPP1 is associated with poor response to steroid therapy in primary FSGS.

Successful treatment of six patients with neuroleptic malignant syndrome associated with myoglobulinemic acute renal failure.

Neuroleptic malignant syndrome is a rare but potentially lethal, rare reaction to neuroleptics which is characterized by altered levels of consciousness, extrapyramidal effects, autonomic instability, hyperthermia, and elevated serum creatine phosphokinase levels. The most serious complication of neuroleptic malignant syndrome is acute renal failure. We investigated six cases of neuroleptic malignant syndrome associated with myoglobulinemic acute renal failure due to rhabdomyolysis and effect of hemodialysis or hemodiafiltration. The patients were five males and one female with a mean age of 43.5 yr. All of the patients, who developed acute renal failure induced from rhabdomyolysis, had previously received butyrophenone (haloperidol), phenothiazine, benzamide, iminomide, benzisoxazole, antidepressants, and hypnotics (benzodiazepine and barbiturate) for the treatment of schizophrenia. The clinical manifestations of neuroleptic malignant syndrome were characterized by altered consciousness, muscle rigidity and weakness, fever, and excessive perspiration. The peak laboratory data were blood urea nitrogen 102 +/- 26 (mean +/- SD) mg/dL, serum creatinine 9.1 +/- 2.1 mg/dL, serum creatine phosphokinase 229,720 +/- 289,940 IU/L, and all of them developed oliguric acute renal failure. Dantrolene sodium administration was given to five cases and hemodialysis or hemodiafiltration was performed in all of them. The serum creatinine level after hemodialysis or hemodiafiltration was 1.4 +/- 1.0 mg/dL. All patients were successfully cured of acute renal failure by hemodialysis or hemodiafiltration. As a result, myoglobulinemic acute renal failure associated with neuroleptic malignant syndrome was successfully treated by hemodialysis or hemodiafiltration.

Catastrophic antiphospholipid antibody syndrome following initiation of hemodialysis.

Antiphospholipid syndrome (APS) is associated with arterial and venous thrombosis, pregnancy morbidity, and thrombocytopenia. Some APS patients develop rapid and disseminated microthrombosis and are known as having catastrophic APS or CAPS. We document here a case of CAPS in a patient who presented with various clinical symptoms and serious abnormalities of blood coagulation following initiation of hemodialysis after bilateral nephrectomy due to renal cancer. The patient developed multiple organ symptoms, including melena, visual disturbances, skin eruptions, lymph node swelling, urinary tract bleeding, backache, arteriovenous fistula occlusion, and chest pain. Based on the clinical course and serological and histological examinations, a diagnosis of CAPS was established. The patient recovered by following intensive anticoagulation and steroid therapy. Although CAPS is rare, once symptoms develop the condition deteriorates rapidly. Because of the associated high mortality, early diagnosis and prompt treatment are necessary.

Up-regulated interleukin-4 production by peripheral T-helper cells in idiopathic membranous nephropathy.

BACKGROUND: Helper T (Th) cells are classified into Th1 and Th2 subsets based on cytokine production and the Th1/Th2 paradigm explains differences in inflammatory effector pathways in various human diseases. Membranous nephropathy (MN) is an immune complex disease associated with Th2 nephritogenic immune response. However, overproduction of interleukin (IL)-4, a principal Th2 cytokine, has not been demonstrated. We investigated Th1/Th2 cytokine production by peripheral Th cells and its association with the degree of proteinuria in MN. METHODS: We analysed production of Th1/Th2 cytokines, interferon (IFN)-gamma and IL-4 by peripheral Th cells, using an intracellular cytokine detection method with flow cytometry in patients with MN (n = 24). The data were compared with data from healthy subjects (n = 51), subjects with minimal change nephrotic syndrome (MCNS; n = 13) and subjects with focal segmental glomerulosclerosis (FSGS; n = 12). We compared the percentages of IFN-gamma+ and IL-4+ Th cells and the peripheral Th1/Th2 ratio (IFN-gamma/IL-4 ratio) among the four groups. We also examined the association of IFN-gamma and IL-4 production with clinical parameters of MN. RESULTS: The mean percentage of IL-4+ cells in MN (3.9+/-1.2%) was significantly higher than in the control (2.4+/-1.0%), MCNS (2.3+/-1.4%) and FSGS (2.3+/-1.2%) groups (P<0.001, respectively). The Th1/Th2 ratio was significantly lower in MN (5.3+/-2.0) than in the control (8.2+/-4.2, P<0.05), MCNS (10.0+/-5.3, P<0.01) and FSGS (10.2+/-5.3, P<0.01) groups. Moreover, the percentage of IL-4+ cells correlated significantly with the amount of proteinuria in MN (r = 0.57, P<0.01). CONCLUSIONS: IL-4 production by peripheral Th cells is up-regulated in patients with MN and correlated with the severity of proteinuria. Intracellular cytokine analysis could be a useful index in idiopathic MN.