Renal tamponade in a patient with hydronephrosis-related Page kidney.

A 48-year-old woman presented with hyperreninemic hypertension and renal dysfunction and was diagnosed with hydronephrosis-related Page kidney. The pathophysiology was "renal tamponade", in which the kidney was compressed by the renal pelvis and Gerota's fascia, resulting in intrarenal microvascular ischemia. Ureteral stent placement promptly improved the hyperreninemic hypertension and renal dysfunction, and additional perirenal fluid drainage gradually improved these conditions. These observations indicated the following three points. First, renal compression-induced renin-angiotensin-aldosterone system upregulation plays an important role in the pathogenesis of Page kidney. Second, physicians should consider perirenal fluid drainage as a therapeutic option in addition to ureteral stenting in patients with hydronephrosis-related Page kidney. Third, bilateral perirenal subcapsular hematomas in this case could be caused by hydronephrosis. Hydronephrosis-induced intrarenal pressure elevation possibly caused chronic perirenal subcapsular hemorrhage at the vulnerable sites of the renal cortex and peeling of the renal capsule from the cortex, resulting in the bilateral massive subcapsular hematomas and Page kidney.

Seroma as a Rare Complication of Autologous Arteriovenous Fistula Creation in the Forearm of a Hemodialysis Patient: A Case Report.

Aim of the study: Seromas are rarely reported as complications of autologous arteriovenous fistula creation. Case description: An 89-year-old woman was hospitalized for hemodialysis and underwent an autologous arteriovenous fistula creation in the forearm. During cephalic vein expansion using a heparinized saline solution, leakage occurred. A suture was placed to control the leakage, and a Penrose drain was inserted. Serosanguineous drainage ceased on postoperative day two; however, a seroma occurred approximately two weeks after the surgery. Follow-up ultrasonography revealed no growth tendency; therefore, excision and aspiration were unnecessary. Conclusion: This seroma was associated with postoperative dead space, surgical technique, and patient clinical status. Sufficient preoperative ultrasonographic vascular mapping is required to avoid inappropriate handling of veins and prevent seroma formation. Postoperative ultrasonographic follow-up is recommended due to the future risk of fistula dysfunction and infection associated with seroma enlargement, which may necessitate surgical seroma excision.

Acute Brachial Arterial Embolic Occlusion Following Anticoagulant Discontinuation in a Renal Biopsy of a Nephrotic Syndrome Patient.

A 73-year-old woman with atrial fibrillation treated with rivaroxaban was hospitalized for nephrotic syndrome. After discontinuation of rivaroxaban to lower the risk of hemorrhagic events, a renal biopsy was performed. Rivaroxaban was scheduled to resume a week after the biopsy to prevent renal hemorrhaging. However, she developed acute brachial arterial embolic occlusion and mural thrombosis in the abdominal aorta before resuming rivaroxaban. If immune-mediated renal diseases are suspected in anticoagulated patients at a risk of thrombotic events, physicians should consider initiating glucocorticoid therapy without a renal biopsy in order to avoid hemorrhagic and thrombotic events.

Vancomycin Intoxication and Cefepime-induced Encephalopathy Treated by Abdominal Drainage of Massive Ascites in Addition to Online Hemodiafiltration.

A patient with recurrent plasmacytoma with massive ascites exhibited vancomycin intoxication and cefepime-induced encephalopathy due to renal dysfunction. The ascitic accumulation of these drugs was suspected because of the refractory intoxicated state. To remove these drugs that had accumulated in the blood and ascites, abdominal drainage was performed in addition to online hemodiafiltration. If patients with renal dysfunction and massive ascites develop vancomycin intoxication and cefepime-induced encephalopathy that cannot be improved by drug discontinuation, physicians should suspect ascitic accumulation and evaluate the ascitic concentration. Furthermore, if a high accumulation in massive ascites occurs, physicians should perform abdominal drainage along with blood purification.

Conditional Deletion of Smad1 Ameliorates Glomerular Injury in Progressive Glomerulonephritis.

Matrix expansion and cell proliferation are concomitantly observed in various glomerular injuries. However, the molecular mechanisms responsible for these changes have not been fully elucidated. We have reported that Smad1 is a key signalling molecule that regulates the transcription of type IV collagen (Col4) in mesangial matrix expansion and is thereby involved in glomerular injury in an acute model of glomerulonephritis. In this study, we addressed the role of Smad1 signalling in accelerated nephrotoxic nephritis (NTN), a model of progressive glomerulonephritis, using conditional deletion of Smad1 in Rosa26CreERT2 mice (Smad1-CKO). Mesangial matrix expansion in the Smad1-CKO mice with NTN was significantly inhibited compared with that in wild type mice with NTN, which was consistent with the decrease in Col4 expression level. On the other hand, STAT3 activation and cell proliferation were not influenced by Smad1 deletion in the NTN model. Therefore, we investigated another factor that activates cell proliferation in the absence of Smad1. Id2 induced VEGF secretion and subsequent STAT3 activation, independently of Smad1 expression in mouse mesangial cells. Here we show that Smad1 plays an important role in the development of glomerular injury without affecting cell proliferation, in progressive glomerulonephritis.

Patient-Specific Relationship Between Hydraulic Permeability of Microvasculature and the Extent of Burden of Excess Fluid in Hemodialysis Patients.

We have reported a significant correlation between hydraulic permeability of microvasculature adjusted with ultrafiltration rate (AdjLpst) and excess fluid divided by dry weight (ExF/DW) in a cross-sectional study of hemodialysis patients. We aimed to study longitudinally whether a similar relationship between them exists in each patient. Twelve hemodialysis (HD) patients in whom AdjLpst and ExF/DW had been measured more than four times (total of 85 measurements) were enrolled. AdjLpst was calculated by monitoring blood volume during HD. ExF was calculated from the fluid volume measured via bioimpedance spectroscopy. The borders of overhydration were 1.66 mL/mm Hg per min for AdjLpst and a positive value for ExF/DW. There was a significant correlation between AdjLpst and ExF/DW (r = 0.517). When the 85 measurements were classified into four quadrants according to ExF/DW and AdjLpst, the evaluations of fluid status agreed in 66 measurements. In six patients, significant positive correlations were found. In nine patients, equal to or more than 80.0% of evaluations by AdjLpst and those by ExF/DW agreed. In only one patient was there neither significant correlation nor agreement. AdjLpst of two patients suffering from chronic heart failure and microscopic polyangiitis was reduced compared with that of others loaded with the same extent of excess fluid. We concluded that there was a significant correlation between AdjLpst and ExF/DW and high agreement between evaluation by AdjLpst and evaluation by ExF/DW in the majority of patients. However, the relationship between them was patient-specific to some extent.

Molecular Markers of Tubulointerstitial Fibrosis and Tubular Cell Damage in Patients with Chronic Kidney Disease.

In chronic kidney disease (CKD), progressive nephron loss causes glomerular sclerosis, as well as tubulointerstitial fibrosis and progressive tubular injury. In this study, we aimed to identify molecular changes that reflected the histopathological progression of renal tubulointerstitial fibrosis and tubular cell damage. A discovery set of renal biopsies were obtained from 48 patients with histopathologically confirmed CKD, and gene expression profiles were determined by microarray analysis. The results indicated that hepatitis A virus cellular receptor 1 (also known as Kidney Injury Molecule-1, KIM-1), lipocalin 2 (also known as neutrophil gelatinase-associated lipocalin, NGAL), SRY-box 9, WAP four-disulfide core domain 2, and NK6 homeobox 2 were differentially expressed in CKD. Their expression levels correlated with the extent of tubulointerstitial fibrosis and tubular cell injury, determined by histopathological examination. The expression of these 5 genes was also increased as kidney damage progressed in a rodent unilateral ureteral obstruction model of CKD. We calculated a molecular score using the microarray gene expression profiles of the biopsy specimens. The composite area under the receiver operating characteristics curve plotted using this molecular score showed a high accuracy for diagnosing tubulointerstitial fibrosis and tubular cell damage. The robust sensitivity of this score was confirmed in a validation set of 5 individuals with CKD. These findings identified novel molecular markers with the potential to contribute to the detection of tubular cell damage and tubulointerstitial fibrosis in the kidney.

Bone Morphogenetic Protein 4 and Smad1 Mediate Extracellular Matrix Production in the Development of Diabetic Nephropathy.

Diabetic nephropathy is the leading cause of end-stage renal disease. It is pathologically characterized by the accumulation of extracellular matrix in the mesangium, of which the main component is α1/α2 type IV collagen (Col4a1/a2). Recently, we identified Smad1 as a direct regulator of Col4a1/a2 under diabetic conditions in vitro. Here, we demonstrate that Smad1 plays a key role in diabetic nephropathy through bone morphogenetic protein 4 (BMP4) in vivo. Smad1-overexpressing mice (Smad1-Tg) were established, and diabetes was induced by streptozotocin. Nondiabetic Smad1-Tg did not exhibit histological changes in the kidney; however, the induction of diabetes resulted in an ∼1.5-fold greater mesangial expansion, consistent with an increase in glomerular phosphorylated Smad1. To address regulatory factors of Smad1, we determined that BMP4 and its receptor are increased in diabetic glomeruli and that diabetic Smad1-Tg and wild-type mice treated with a BMP4-neutralizing antibody exhibit decreased Smad1 phosphorylation and ∼40% less mesangial expansion than those treated with control IgG. Furthermore, heterozygous Smad1 knockout mice exhibit attenuated mesangial expansion in the diabetic condition. The data indicate that BMP4/Smad1 signaling is a critical cascade for the progression of mesangial expansion and that blocking this signal could be a novel therapeutic strategy for diabetic nephropathy.

[A case of thrombotic microangiopathy with glomerular subendothelial IgA deposition due to bevacizumab].

Bevacizumab, an inhibitor of vascular endothelial growth factor, is approved for the treatment of various cancers, but the incidence of proteinuria as a side effect has been reported to be 2-64%. We report a case of renal impairment due to thrombotic microangiopathy (TMA) accompanied with glomerular subendothelial deposition of IgA resulting from bevacizumab administration. A 57-year-old female with advanced breast cancer, to whom bevacizumab had been administered from October 2012, developed proteinuria and epithelial casts in her urine about a month later. Serum creatinine remained at 0.7-0.8 mg/dL until June 2013, but gradually increased to 1.3 mg/dL in September. She was referred to our hospital because her renal function had not improved despite termination of bevacizumab, and a renal biopsy was performed in October. At that time, the levels of proteinuria, serum creatinine and serum IgA were high at 1.3 g/g x Cr, 1.6 mg/dL and 430 mg/dL, respectively. Histological examinations showed prominent IgA deposits in the subendothelial area and glomerular infiltration of CD68 positive cells in addition to features of TMA, such as narrowed glomerular capillary lumina and double contours of the basement membranes. In consideration of her clinical history, a diagnosis of bevacizumab-induced TMA was made. Through follow-up care without readministration of bevacizumab, epithelial casts in her urine disappeared, and proteinuria decreased to 0.62 g/g x Cr in November. Serum creatinine remains high at around 1.3 mg/dL, but has not elevated further. Serum IgA gradually decreased and reached 289 mg/dL in April 2014. TMA due to bevacizumab described in several other reports was also accompanied by glomerular IgA deposition, thus a differential diagnosis of IgA nephropathy is required. TMA was recently added to a section of "significant adverse effects" in the package insert of bevacizumab. Nephrologists should be fully aware of this drug-induced nephropathy.

Protein inhibitor of activated STAT, PIASy regulates α-smooth muscle actin expression by interacting with E12 in mesangial cells.

Phenotypic transformation of mesangial cells (MCs) is implicated in the development of glomerular disease; however, the mechanisms underlying their altered genetic program is still unclear. α-smooth muscle actin (α-SMA) is known to be a crucial marker for phenotypic transformation of MCs. Recently, E-boxes and the class I basic helix-loop-helix proteins, such as E12 have been shown to regulateα-SMA expression. Therefore, we tried to identify a novel E12 binding protein in MCs and to examine its role in glomerulonephritis. We found that PIASy, one of the protein inhibitors of activated STAT family protein, interacted with E12 by yeast two-hybrid screens and coimmunopreciptation assays. Overexpression of E12 significantly enhanced theα-SMA promoter activity, and the increase was blocked by co-transfection of PIASy, but not by a PIASy RING mutant. In vivo sumoylation assays revealed that PIASy was a SUMO E3 ligase for E12. Furthermore, transforming growth factor-ß (TGF-ß) treatment induced expression of both PIASy and E12, consistent with α-SMA expression. Moreover, reduced expression of PIASy protein by siRNA specific for PIASy resulted in increased TGF-ß-mediated α-SMA expression. In vivo, PIASy and E12 were dramatically upregulated along with α-SMA and TGF-ß in the proliferative phase of Thy1 glomerulonephritis. Furthermore, an association between PIASy and E12 proteins was observed at day 6 by IP-western blotting, but not at day 0. These results suggest that TGF-ß up-regulates PIASy expression in MCs to down-regulateα-SMA gene transcription by the interaction with E12.

Comparison of the psychosocial quality of life in hemodialysis patients between the elderly and non-elderly using a visual analogue scale: the importance of appetite and depressive mood.

AIM: The number of hemodialysis (HD) patients is increasing along with their mean age in Japan. The assessment of their psychosocial status and quality of life (QOL) is therefore becoming more and more important along with laboratory data or comorbidities. METHODS: We examined the psychosocial status of 211 HD patients (72 elderly and 139 non-elderly) and compared the difference between elderly and non-elderly patients using a visual analogue scale (VAS). We then examined how QOL affected mortality rate in 3-year prospective follow up. We assessed 10 items of QOL: health condition, appetite, sleep, mood, memory, family relationships, friendship, economical status, life satisfaction in daily life, and happiness with qualified self-evaluating questionnaires along with laboratory data and comorbidities. Furthermore, we investigated the correlation between the scores of mood and geriatric depression scale (GDS)-15. RESULTS: There was no difference in VAS scores between elderly and non-elderly patients. Lower VAS scores for appetite and mood correlated with higher mortality in HD patients, especially in the non-elderly. VAS scores for mood correlated with GDS-15 in HD patients. CONCLUSIONS: More attention should be paid to appetite and the diagnosis and therapy of depressive mood to improve the prognosis of HD patients, especially for the non-elderly.

SOX9 protein induces a chondrogenic phenotype of mesangial cells and contributes to advanced diabetic nephropathy.

Diabetic nephropathy (DN) is the most important chronic kidney disease. We previously reported that Smad1 transcriptionally regulates the expression of extracellular matrix in DN. Phenotypic change in mesangial cells (MCs) is a key pathologic event in the progression of DN. The aim of this study is to investigate a novel mechanism underlying chondrogenic phenotypic change in MCs that results in the development of DN. MCs showed chondrogenic potential in a micromass culture, and BMP4 induced the expression of chondrocyte markers (SRY-related HMG Box 9 (SOX9) and type II collagen (COL2)). Advanced glycation end products induced the expression of chondrocyte marker proteins downstream from the BMP4-Smad1 signaling pathway in MCs. In addition, hypoxia also induced the expression of BMP4, hypoxia-inducible factor-1α (HIF-1α), and chondrocyte markers. Overexpression of SOX9 caused ectopic expression of proteoglycans and COL2 in MCs. Furthermore, forced expression of Smad1 induced chondrocyte markers as well. Dorsomorphin inhibited these inductions. Glomerular expressions of HIF-1α, BMP4, and chondrocyte markers were observed in diabetic nephropathy mice. These positive stainings were observed in mesangial sclerotic lesions. SOX9 was partially colocalized with HIF-1α and BMP4 in diabetic glomeruli. BMP4 knock-in transgenic mice showed not only similar pathological lesions to DN, but also the induction of chondrocyte markers in the sclerotic lesions. Here we demonstrate that HIF-1α and BMP4 induce SOX9 expression and subsequent chondrogenic phenotype change in DN. The results suggested that the transdifferentiation of MCs into chondrocyte-like cells in chronic hypoxic stress may result in irreversible structural change in DN.

An autopsy case of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) with intestinal bleeding in chronic renal failure.

A 50-year-old man who underwent hemodialysis (HD) at local outpatient HD center due to end-stage renal disease (ESRD) was transferred to our hospital because of pneumonia. He had severe emaciation and past history of congestive heart failure. Presenting symptoms almost consistently involved difficulty in hearing and recurrent attacks of migraine-like headaches. He was diagnosed with dilated cardiomyopathy, showing diastolic mechanical dyssynchrony by tissue Doppler echocardiography. On the day of death, he had hematemesis and hemorrhagic shock. Autopsy revealed perforation of duodenum, and genetic analysis using mitochondrial DNA from cardiac muscle and iliopsoas muscle revealed a 3243A > G mutation in the mitochondrial tRNA(Leu(UUR)) gene, which is related to mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Multiple organ failure due to the mutation of mitochondrial DNA with gastrointestinal bleeding is not a common.

Activation of Src mediates PDGF-induced Smad1 phosphorylation and contributes to the progression of glomerulosclerosis in glomerulonephritis.

Platelet-derived growth factor (PDGF) plays critical roles in mesangial cell (MC) proliferation in mesangial proliferative glomerulonephritis. We showed previously that Smad1 contributes to PDGF-dependent proliferation of MCs, but the mechanism by which Smad1 is activated by PDGF is not precisely known. Here we examined the role of c-Src tyrosine kinase in the proliferative change of MCs. Experimental mesangial proliferative glomerulonephritis (Thy1 GN) was induced by a single intravenous injection of anti-rat Thy-1.1 monoclonal antibody. In Thy1 GN, MC proliferation and type IV collagen (Col4) expression peaked on day 6. Immunohistochemical staining for the expression of phospho-Src (pSrc), phospho-Smad1 (pSmad1), Col4, and smooth muscle α-actin (SMA) revealed that the activation of c-Src and Smad1 signals in glomeruli peaked on day 6, consistent with the peak of mesangial proliferation. When treated with PP2, a Src inhibitor, both mesangial proliferation and sclerosis were significantly reduced. PP2 administration also significantly reduced pSmad1, Col4, and SMA expression. PDGF induced Col4 synthesis in association with increased expression of pSrc and pSmad1 in cultured MCs. In addition, PP2 reduced Col4 synthesis along with decreased pSrc and pSmad1 protein expression in vitro. Moreover, the addition of siRNA against c-Src significantly reduced the phosphorylation of Smad1 and the overproduction of Col4. These results provide new evidence that the activation of Src/Smad1 signaling pathway plays a key role in the development of glomerulosclerosis in experimental glomerulonephritis.

Angio-embolization of renal artery pseudoaneurysm after renal biopsy: a case report.

Renal artery pseudoaneurysm is a rare clinical entity that has been reported after renal biopsy, percutaneous renal surgery, penetrating trauma, and rarely blunt renal trauma. We present the case of a 37-year-old man with ruptured renal artery pseudoaneurysm accompanied by massive gross hematuria, urinary clot retention, and bladder tamponade, which were the presenting signs seven hours after renal biopsy. Abdominal CT scan showed a large perinephric, intracapsular hematoma of left kidney. His angiogram revealed a left renal segmental artery pseudoaneurysm that measured 1 cm x 1 cm. He was successfully treated by selective embolization of the arterial branch supplying the pseudoaneurysm.

Involvement of lupus enteritis in a patient with lupus cystitis and nephritis.

We present the case of a patient with lupus enteritis accompanied by both lupus cystitis and lupus nephritis without a history of systemic lupus erythematosus. The patient had a 2-month history of diarrhea and pollakiuria and was admitted to our hospital. Physical examination showed abdominal tenderness. Laboratory data revealed reductions in both total protein and albumin, elevated serum creatinine levels, and elevated antinuclear and anti-Smith antibodies. Urinalysis revealed proteinuria. Stool and urine cultures were negative. Abdominal computed tomography revealed diffuse edematous wall thickening, dilatation of the small intestine suggesting paralytic ileus, and irregular wall thickening of the urinary bladder. Histological results of the cystic and renal biopsies revealed interstitial cystitis and membranous nephropathy which were suggestive of lupus cystitis and lupus nephritis, respectively. The patient's gastrointestinal symptoms were finally diagnosed as resulting from lupus enteritis. After initiating 30 mg oral prednisolone daily, the diarrhea and pollakiuria subsided, and renal function became normal. Lupus enteritis should always be considered in the differential diagnosis when patients complaining of chronic diarrhea of unknown etiology are encountered.