Relationship Between Rectal Swab and Tissue Samples in Mucosa-associated Microbiota in Patients With Inflammatory Bowel Disease.

BACKGROUND: Gut mucosa-associated microbiota is more closely correlated with disease phenotypes than fecal microbiota; however sampling via tissue biopsy is more invasive and uncomfortable. Rectal swab may be a suitable substitute for tissue biopsy, but its effectiveness is controversial. This study aimed to evaluate differences in the microbiota at these sites in patients with inflammatory bowel disease (IBD). METHODS: Inflammatory bowel disease patients and a control group were enrolled when surveillance colonoscopy was scheduled. Samples of colon biopsy tissues, rectal swabs during colonoscopy, and feces before bowel preparation were collected to analyze microbial composition. To explore the short-term effects of bowel preparation on swab microbiota, prepreparation swab samples were also collected from 27 IBD patients. RESULTS: A total of 33 Crohn's disease, 54 ulcerative colitis, and 21 non-IBD patients were enrolled. In beta diversity analysis, fecal microbiota clearly differed from swab and tissue microbiota in the 3 disease groups. The swab microbiota was closer to, but still different from, the tissue microbiota. Consistently, we identified that swab samples differed more in abundant genera from feces than from tissue. Beta diversity analysis did not reveal a difference in swab microbiota before and after bowel preparation, but the genus composition of most individuals varied markedly. CONCLUSIONS: Swab microbiota more closely resembled tissue microbiota relative to fecal microbiota, but there were still differences. Bowel preparation did not alter the overall swab microbiota in the short term but markedly changed the microbial composition in most patients.

All-Cause Standardized Mortality Ratio in Hemodialysis and Peritoneal Dialysis Patients: A Nationwide Population-Based Cohort Study.

Patients with end-stage renal disease (ESRD) are at a higher mortality risk compared with the general population. Previous studies have described a relationship between mortality and patients with ESRD, but the data on standardized mortality ratio (SMR) corresponding to different causes of death in patients undergoing hemodialysis (HD) and peritoneal dialysis (PD) are limited. This study was designed as a nationwide population-based retrospective cohort study. Incident dialysis patients between January 2000 and December 2015 in Taiwan were included. Using data acquired from the Taiwan Death Registry, SMR values were calculated and compared with the overall survival. The results showed there were a total of 128,966 patients enrolled, including 117,376 incident HD patients and 11,590 incident PD patients. It was found that 75,297 patients (58.4%) died during the period of 2000-2017. The overall SMR was 5.21. The neoplasms SMR was 2.11; the endocrine, nutritional, metabolic, and immunity disorders SMR was 13.53; the circulatory system SMR was 4.31; the respiratory system SMR was 2.59; the digestive system SMR was 6.1; and the genitourinary system SMR was 27.22. Therefore, more attention should be paid to these diseases in clinical care.

Secreted Neutrophil Gelatinase-Associated Lipocalin Shows Stronger Ability to Inhibit Cyst Enlargement of ADPKD Cells Compared with Nonsecreted Form.

Polycystic kidney disease (PKD) is one of the most common inherited diseases and is characterized by the development of fluid-filled cysts along multiple segments of the nephron. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of PKD, which is caused by mutations in either PKD1 or PKD2 genes that encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. As ADPKD progresses, cysts enlarge and disrupt normal kidney architecture, eventually leading to kidney failure. Our previous study showed that overexpression of exogenous kidney-specific neutrophil gelatinase-associated lipocalin (NGAL) reduced cyst progression and prolonged the lifespan of ADPKD mice (Pkd1L3/L3, 2L3 for short). In this study, we attempted to explore the underlying mechanism of reduced cyst progression in the presence of NGAL using immortalized 2L3 cells. The results of MTT and BrdU incorporation assays showed that recombinant mouse NGAL (mNGAL) protein significantly decreased the viability and proliferation of 2L3 cells. Flow cytometry and western blot analyses showed that mNGAL inhibited activation of the ERK and AKT pathways and induced apoptosis and autophagy in 2L3 cells. In addition, a 3D cell culture platform was established to identify cyst progression in 2L3 cells and showed that mNGAL significantly inhibited cyst enlargement in 2L3 cells. Overexpression of secreted mNGAL (pN + LS) and nonsecreted mNGAL (pN - LS) repressed cell proliferation and cyst enlargement in 2L3 cells and had effects on markers involved in proliferation, apoptosis, and autophagy. However, secreted mNGAL had a more pronounced and consistent effect than that of nonsecreted form. These results reveal that secreted mNGAL has stronger ability to inhibit cyst enlargement of ADPKD cells than that of nonsecreted form. These findings could help to identify strategies for the future clinical treatment of ADPKD.

Large deletion of Wdr19 in developing renal tubules disrupts primary ciliogenesis, leading to polycystic kidney disease in mice.

WD repeat domain 19 (Wdr19) is a major component of the intraflagellar transport (IFT) machinery, which is involved in the function of primary cilia. However, the effects of Wdr19 on primary cilia formation, cystogenesis, and polycystic kidney disease (PKD) progression remain unclear. To study these effects, we generated three lines of kidney-specific conditional knockout mice: Wdr19-knockout (Wdr19-KO, Wdr19f/- ::Cdh16-CreTg/0 ), Pkd1-knockout (Pkd1-KO, Pkd1f/- ::Cdh16-CreTg/0 ), and Wdr19/Pkd1-double knockout (Wdr19&Pkd1-dKO, Wdr19f/- ;Pkd1f/- ::Cdh16-CreTg/0 ) mice. Ultrastructural analysis using transmission electron microscopy (TEM) indicated that the primary cilia were almost absent at postnatal day 10 in Wdr19-KO mice compared with Pkd1-KO and wild-type (WT) mice. However, the primary cilia appeared structurally normal even if malfunctional in Pkd1-deficient cysts. The Pkd1-KO mice had the most severe PKD progression, including the shortest lifespan (14 days) and the largest renal cysts, among the three knockout lines. Thus, the molecular mechanism of renal cystogenesis in Wdr19-KO mice (primary cilia abrogation) was different from that in Pkd1-KO mice (primary cilia malfunction). In summary, Wdr19 deficiency leads to primary cilia abrogation and renal cyst formation. Wdr19 is primarily proposed to participate in retrograde IFT and to be crucial for the construction of primary cilia, which are critical organelles for tubulogenesis in the developing kidneys. © 2022 The Pathological Society of Great Britain and Ireland.

Rhabdomyosarcoma in a child with nephrotic syndrome treated with cyclosporine: a case report with literature review.

BACKGROUND: In patients with frequently relapsing nephrotic syndrome, immunosuppressive therapy such as cyclosporine are often required to maintain remission. Cyclosporine has been noted to have tumorgenesis effects. In this case report, we present a child with relapsing nephrotic syndrom developed a rhabdomyosarcoma on her tongue after adout 4 years of continual immunosuppressive therapy. CASE PRESENTATION: A 2-year-old female child had nephrotic syndrome (urine protein-creatinine ratio 749.1 mg/mg; blood urea nitrogen 11 mg/dL; serum creatinine 0.3 mg/dL; and serum albumin 1.8 g/dL.) Proteinuria resolved on treatment with daily prednisolone for 4 weeks at the dose of 45 mg (2.5 mg/kg/day) but recurred with taper from 25 mg/day to 10 mg/day. At least five more episodes of relapse occurred within about a 3-year period. After the third relapse, she was treated with prednisolone and cyclosporine (at initial dose of 50 mg/day [1.7 mg/kg/day]) for immunosuppression. About 4 years after the diagnosis of nephrotic syndrome had been made, an embryonal rhabdomyosarcoma developed on her tongue. The cancer was treated with TPOG-RMS-LR protocol, with vincristine, actinomycin, and cyclophosphamide. Magnetic resonance imaging scan, performed about 3 years after the start of TPOG-RMS-LR therapy, revealed complete remission of the cancer. CONCLUSIONS: Although treatment with cyclosporine cannot be conclusively implicated as the cause the rhabdomyosarcoma in this patient, the association should prompt consideration of its use in the treatment of frequently relapsing nephrotic syndrome in children.

Kidney-based in vivo model for drug-induced nephrotoxicity testing.

The need is critical and urgent for a real-time, highly specific, and sensitive acute kidney injury biomarker. This study sought to establish a sensitive and specific Miox-NanoLuc transgenic mouse for early detection of drug-induced nephrotoxicity. We generated Miox-NanoLuc transgenic mice with kidney-specific NanoLuc overexpression. Our data showed that Miox-NanoLuc-produced luminescence was kidney-specific and had good stability at room temperature, 4 °C, - 20 °C, and repeated freeze-thaw cycles. Serum levels of BUN and creatinine were significantly increased at day 2 or 3 in cisplatin-treated mice and at day 5 in aristolochic acid (AAI)-treated mice. Particularly, the serum and urine Miox-NanoLuc luminescence levels were significantly increased at day 1 in cisplatin-treated mice and at day 3 in AAI-treated mice. Renal pathological analysis showed that the kidney sections of cisplatin-treated mice at day 5 and AAI-treated mice at day 13 showed cytolysis and marked vacuolization of tubular cells. In conclusion, we developed a new platform to early quantify drug-induced nephrotoxicity before serum BUN and creatinine levels increased and pathological tubular cell injury occurred. This model may serve as an early detection for drug- and food-induced nephrotoxicity and as an animal model to investigate tubular cell injury.

Factors associated with long-term progression of pediatric chronic kidney disease of nonglomerular etiologies.

BACKGROUND/PURPOSE: The aims of this study were to determine the long-term associated factors for chronic kidney disease (CKD) progression in a pediatric group with non-glomerular (non-GN) etiologies. METHODS: Pediatric patients with a presumptive diagnosis of CKD were enrolled to this study. Recorded information included demographic and laboratory information. We included the patients with non-GN etiologies and investigated the factors including systolic and diastolic blood pressure (BP), proteinuria, and anemia status in association with reductions in the estimated glomerular filtration rate (eGFR). RESULTS: A total of 308 children were enrolled and the mean duration of follow-up was 4.40 ± 3.53 years. Median baseline age was 5 years old and the males represented 55% of all patients. One-unit increased baseline systolic BP z-score was associated with 1.2 ml/min per 1.73 m2 (95% CI = -2 to -0.5) faster rate of eGFR decline. The presence of baseline proteinuria and anemia were also associated with 4.1 ml/min per 1.73 m2 (95% CI = -5.7 to -2.5) and 2.2 ml/min per 1.73 m2 (95% CI = -3.6 to -0.8) more rapid eGFR declination, respectively. Hypertension, anemia and proteinuria during the follow-up were also associated with 3.25 ml/min per 1.73 m2 (95% CI = -5.32 to -1.18), 4.34 ml/min per 1.73 m2 (95% CI = -7.25 to -1.43) and 4.97 ml/min per 1.73 m2 (95% CI = -8.23 to -1.71) more rapid eGFR declination, respectively. CONCLUSION: Elevated systolic BP, proteinuria, and anemia are independently associated with CKD progression in pediatric patients with non-GN etiologies.

Safe Nanocomposite-Mediated Efficient Delivery of MicroRNA Plasmids for Autosomal Dominant Polycystic Kidney Disease (ADPKD) Therapy.

There is currently no cure for gene mutation-caused autosomal dominant polycystic kidney disease (ADPKD). Over half of patients with ADPKD eventually develop kidney failure, requiring dialysis or kidney transplantation. Current treatment modalities for ADPKD focus on reducing morbidity and mortality from renal and extrarenal complications of the disease. MicroRNA has been shown to be useful in treating ADPKD. This study combines anti-miRNA plasmids and iron oxide/alginate nanoparticles for conjugation with antikidney antibodies. These nanocomposites can specifically target renal tubular cells, providing a potential treatment for ADPKD. Magnetic resonance imaging and in vivo imaging system results show effective targeting of renal cells. Anti-miRNA plasmids released from the nanocomposites inhibit cell proliferation and cyst formation in the PKD cellular and animal models. The results suggest the novel combination of the anti-miRNA plasmids and nanomaterials provides potential clinical implications for ADPKD treatment.

Is there different risk of cancer among end-stage renal disease patients undergoing hemodialysis and peritoneal dialysis?

Cancer is a global issue in recent decade. Despite this alarming increase in the incidence of cancer, to date, whether the risk of developing cancer differs among peritoneal dialysis (PD) and hemodialysis (HD) patients is still uncertain. In this retrospective cohort study, data were obtained from the National Health Insurance Research Database of Taiwan, which provides coverage to almost 99% of the nation's population. After matching, a total of 4491 (or 3369) incident PD patients and 8982 (or 6738) incident HD patients between 2000 and 2009 were enrolled from the database. In addition, 22,455 (or 16,845) nondialysis patients were selected as a control group. The patients were monitored for the occurrence of cancer until 2010, and their data were analyzed using several different models. In general, the results showed that the risks of hepatocellular, kidney, bladder, extra kidney/bladder urinary tract, and thyroid cancers were higher in dialysis patients. We also compared the risk of cancer between two dialysis groups by using the HD patients as the reference group. The result showed that there is no significant different for each cancer risk between two dialysis groups. In conclusion, dialysis patients had a higher risk of certain types of cancer than those in the nonuremia group. However, there was no significant difference in the cancer risk between the two dialysis groups when compared directly.

Overexpression of exogenous kidney-specific Ngal attenuates progressive cyst development and prolongs lifespan in a murine model of polycystic kidney disease.

Neutrophil gelatinase-associated lipocalin (Ngal) is a biomarker for acute and chronic renal injuries, including polycystic kidney disease (PKD). However, the effect of Ngal on PKD progression remains unexplored. To study this, we generated 3 strains of mice with different expression levels of Ngal within an established PKD model (Pkd1L3/L3): Pkd1L3/L3 (with endogenous Ngal), Pkd1L3/L3; NgalTg/Tg (with endogenous and overexpression of exogenous kidney-specific Ngal) and Pkd1L3/L3; Ngal-/- mice (with Ngal deficiency). Knockout of endogenous Ngal had no effect on phenotypes, cystic progression, or survival of the PKD mice. However, the transgenic mice had a significantly longer lifespan, smaller (but not fewer) renal cysts, and less interstitial fibrosis than the mice without or with endogenous Ngal. Western-blot analyses showed significant increases in Ngal and cleaved caspase-3 and decreases in α-smooth muscle actin, hypoxia-inducible factor 1-α, pro-caspase 3, proliferating cell nuclear antigen, Akt, mammalian target of rapamycin, and S6 Kinase in the transgenic mice as compared with the other 2 strains of PKD mice. Thus, overexpression of exogenous kidney-specific Ngal reduced cystic progression and prolonged the lifespan in PKD mice, was associated with reductions in interstitial fibrosis and proliferation, and augmented apoptosis.

Quantitative analysis of tissue inflammation and responses to treatment in immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, and review of literature.

BACKGROUND/PURPOSE: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a severe autoimmune disease that is caused by regulatory T cell deficiency due to FOXP3 gene mutations. The long-term outcome can be variable depending on the extent of tissue damage caused by autoimmunity and infections, the use of immunosuppressive treatment or sequela of bone marrow transplantation. METHODS: We used immunohistochemical staining to analyze cell types infiltrating the tissue of affected organs from a classic IPEX patient with a splicing mutation (c.736-2A>C) in the FOXP3 gene. Expression of transcription factors that are critical for immune responses including T-bet, GATA-3, RORγt, and FOXP3 were evaluated in various tissue samples. For objective analysis of the distribution of different cell types in tissues, we used an automated microscope-based image acquiring system to assess quantitatively the different cell types by investigating the histopathological changes in the patient's biopsy samples obtained from the intestine and the kidneys before and after treatment. RESULTS: The percentages of cells expressing the TH2-associated transcription factor GATA3 were higher in the IPEX patient before treatment than in controls, suggesting that TH2-type cells contribute to the tissue inflammation of the gut and kidneys in IPEX syndrome. Immunosuppressive treatment effectively decreased the number of effector cells in the kidneys and intestine of the IPEX patient. CONCLUSION: This study provides quantitative evidence that the inflamed intestinal and renal tissues of the IPEX patient contain TH2-type immune effector cells, which decreased in number after immunosuppressive treatment was initiated and the clinical symptoms had improved.

Shorter daily dwelling time in peritoneal dialysis attenuates the epithelial-to-mesenchymal transition of mesothelial cells.

BACKGROUND: Peritoneal dialysis (PD) therapy is known to induce morphological and functional changes in the peritoneal membrane. Long-term exposure to conventional bio-incompatible dialysate and peritonitis is the main etiology of inflammation. Consequently, the peritoneal membrane undergoes structural changes, including angiogenesis, fibrosis, and hyalinizing vasculopathy, which ultimately results in technique failure. The epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MCs) plays an important role during the above process; however, the clinical parameters associated with the EMT process of MCs remain to be explored. METHODS: To investigate the parameters impacting EMT during PD therapy, 53 clinical stable PD patients were enrolled. EMT assessments were conducted through human peritoneal MCs cultured from dialysate effluent with one consistent standard criterion (MC morphology and the expression of an epithelial marker, cytokeratin 18). The factors potentially associated with EMT were analyzed using logistic regression analysis. Primary MCs derived from the omentum were isolated for the in vitro study. RESULTS: Forty-seven percent of the patients presented with EMT, 28% with non-EMT, and 15% with a mixed presentation. Logistic regression analysis showed that patients who received persistent PD therapy (dwelling time of 24 h/day) had significantly higher EMT tendency. These results were consistent in vitro. CONCLUSIONS: Dwelling time had a significant effect on the occurrence of EMT on MCs.

Invasive pneumococcal pneumonia is the major cause of paediatric haemolytic-uraemic syndrome in Taiwan.

AIM: Streptococcus pneumoniae-associated haemolytic uraemic syndrome (SP-HUS) is a major concern of paediatric acute renal failure in Taiwan; it leads to significant morbidity and mortality during the acute phase and to long-term morbidity after an acute episode. METHODS: Twenty children diagnosed with HUS between 1 May 1995, and 31 December 2008 was enrolled. Clinical variables related to laboratory data, organ involved, and outcomes were examined between patients with and without SP-HUS. RESULTS: Thirteen of the 20 (13/20, 65%) patients required dialysis, nine (9/20, 45.0%) developed hepatic dysfunction, disseminated intravascular coagulation (DIC), gastrointestinal bleeding, and hypertension, respectively. They were the second most common extrarenal complication except empyema (11/20, 55%). Two (10%) died and seven (35%) of the survivors developed long-term renal morbidity. Twelve of the 20 patients (60%) were diagnosed with SP-HUS. Younger age, female children, higher white blood cell count, higher alanine transaminase, higher lactate dehydrogenase and high incidence of DIC were significantly common in SP-HUS cases. All SP-HUS cases were complicated with pleural effusion, empyema, or both. Positive Thomsen-Freidenreich antigen (T-Ag) activation was 83% sensitive and 100% specific for SP-HUS, and a positive direct Coombs' test was 58% sensitive and 100% specific. CONCLUSION: Invasive pneumococcal infection is the most common cause of HUS in Taiwan. Positive T-Ag activation and a direct Coombs' test are rapid predictors of SP-HUS in children with invasive pneumonia.

Adjunctive oral methylprednisolone in pediatric acute pyelonephritis alleviates renal scarring.

OBJECTIVE: To determine if glucocorticoids can prevent renal scar formation after acute pyelonephritis in pediatric patients. METHODS: Patients younger than 16 years diagnosed with their first episode of acute pyelonephritis with a high risk of renal scar formation (ie, inflammatory volume ≥ 4.6 mL on technetium-99m-labeled dimercaptosuccinic acid scan [DMSA] or abnormal renal ultrasonography results) were randomly assigned to receive either antibiotics plus methylprednisolone sodium phosphate (1.6 mg/kg per day for 3 days [MPD group]) or antibiotics plus placebo (placebo group) every 6 hours for 3 days. Patients were reassessed by using DMSA 6 months after treatment. The primary outcome was the development of renal scars. RESULTS: A total of 84 patients were enrolled: 19 in the MPD group and 65 in the placebo group. Patient characteristics were similar between the 2 groups, including the acute inflammatory parameters and the initial DMSA result. Renal scarring was found in 33.3% of children treated with MPD and in 60.0% of those who received placebo (P < .05). The median cortical defect volumes on follow-up DMSA were 0.0 mL (range: 0-4.5 mL) and 1.5 mL (range: 0-14.8 mL) for the MPD and placebo groups, respectively (P < .01). Patients in the MPD group experienced faster defervescence after treatment than the placebo group. CONCLUSIONS: Adjunctive oral MPD therapy reduced the occurrence and/or severity of renal scarring after acute pyelonephritis in these hospitalized children who had a high risk of renal scar formation.

Progressive renal distortion by multiple cysts in transgenic mice expressing artificial microRNAs against Pkd1.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common life-threatening inherited diseases, and the PKD1 gene is responsible for most cases of this disease. Previous efforts to establish a mouse model that recapitulates the phenotypic characteristics of ADPKD, which have used conventional or conditional knockout of the mouse orthologue Pkd1, have been unsuccessful or unreliable. In a previous study, we described the generation of a novel Pkd1 hypomorphic allele, in which Pkd1 expression was significantly reduced but not totally blocked. These Pkd1 homozygous mutant mice rapidly developed renal cystic disease, supporting the hypothesis that 'haploinsufficiency' explains development of the ADPKD phenotype. In the present study, we further investigated the Pkd1 haploinsufficiency effect by generating Pkd1 knockdown transgenic mice with co-cistronic expression of two miRNA hairpins specific to Pkd1 transcript and an Emerald GFP reporter driven by a human ubiquitin B promoter. Two transgenic lines which had ∼60-70% reduction of Pkd1 expression developed severe renal cystic disease at a rate similar to that of human ADPKD. These results further support the haploinsufficiency hypothesis, and suggest that the onset and progression of the renal cystic diseases are correlated with the level of Pkd1 expression. The two novel mutant lines of mice appear to be ideal models for the study of ADPKD.

Bacterial virulence factors are associated with occurrence of acute pyelonephritis but not renal scarring.

PURPOSE: We evaluated the influence of patient factors and virulence factors of uropathogenic Escherichia coli on the occurrence of acute pyelonephritis and subsequent renal parenchymal scarring. MATERIALS AND METHODS: We evaluated 80 boys and 45 girls 1 to 180 months old with febrile urinary tract infections who underwent renal scan to diagnose acute pyelonephritis and followup dimercapto-succinic acid scintigraphy at least 6 months later. Urinalysis, white blood cell count, uropathogenic E. coli genotype and vesicoureteral reflux were measured. Voiding cystourethrogram was investigated after acute pyelonephritis was confirmed by renal scan and acute inflammation subsided, about 2 to 4 weeks later. RESULTS: Acute pyelonephritis was significantly more likely to develop in children with urinary tract infections and persistent fever before and after hospitalization, elevated C-reactive protein or positive renal ultrasound findings. E. coli strains with the papG II and iha genes were significantly more likely to occur in patients with acute pyelonephritis. Patients with a fever for more than 3 days and C-reactive protein levels greater than 90.8 mg/l were significantly more likely to have renal scarring. Age was not an independent predictor of acute pyelonephritis, but modified the effect of virulence factors on the development of acute pyelonephritis. CONCLUSIONS: Bacterial virulence factors and host factors are associated with the occurrence of acute pyelonephritis. Host factors such as patient age and vesicoureteral reflux severity modify the influence of virulence factors, although only host factors are associated with the occurrence of renal scarring.

Urinary cytokines and renal Doppler study in Kawasaki disease.

OBJECTIVE: To investigate whether renal vasculitis is the sole cause or merely a contributing cause of renal inflammation in Kawasaki disease (KD). STUDY DESIGN: This prospective study in a university medical center in Taiwan enrolled 24 children with KD between June 2004 and November 2005. All patients underwent a technetium-99 m dimercaptosuccinic acid scintigraphy single-photon emission computed tomography scan, the results of which were used to group the patients with KD as with or without renal involvement. Urine samples underwent a cytokine analysis. Renal Doppler ultrasonography was used to evaluate renal vasculitis by measuring the pulsatility index (PI) and resistance index (RI). RESULTS: Ten of the 24 patients (42%) with renal inflammatory foci were the study group; the remainder composed the control group. Urinary interleukin (IL)-6 levels were significantly higher in the study group (496.7 +/- 310.9 vs 115.0 +/- 65.9 ng/g urinary creatinine; P < .01), as were PI values (1.85 +/- 0.70 vs 1.44 +/- 0.53; P < .05). Urinary IL-6 levels and PI values were significantly (P < .05) correlated. CONCLUSIONS: Increased urinary IL-6 and elevated renal Doppler measures suggest that immune-mediated vasculitis is one of the mechanisms causing renal inflammation in KD.

Mouse kidney progenitor cells accelerate renal regeneration and prolong survival after ischemic injury.

Acute tubular necrosis is followed by regeneration of damaged renal tubular epithelial cells, and renal stem cells are supposed to contribute to this process. The purpose of our study is to test the hypothesis that renal stem cells isolated from adult mouse kidney accelerate renal regeneration via participation in the repair process. A unique population of cells exhibiting characteristics consistent with renal stem cells, mouse kidney progenitor cells (MKPC), was isolated from Myh9 targeted mutant mice. Features of these cells include (1) spindle-shaped morphology, (2) self-renewal of more than 100 passages without evidence of senescence, and (3) expression of Oct-4, Pax-2, Wnt-4, WT-1, vimentin, alpha-smooth muscle actin, CD29, and S100A4 but no SSEA-1, c-kit, or other markers of more differentiated cells. MKPC exhibit plasticity as demonstrated by the ability to differentiate into endothelial cells and osteoblasts in vitro and endothelial cells and tubular epithelial cells in vivo. The origin of the isolated MKPC was from the interstitium of medulla and papilla. Importantly, intrarenal injection of MKPC in mice with ischemic injury rescued renal damage, as manifested by decreases in peak serum urea nitrogen, the infarct zone, and the necrotic injury. Seven days after the injury, some MKPC formed vessels with red blood cells inside and some incorporated into renal tubules. In addition, MKPC treatment reduces the mortality in mice after ischemic injury. Our results indicate that MKPC represent a multipotent adult stem cell population, which may contribute to the renal repair and prolong survival after ischemic injury.

In situ expression of T-helper type 2 immunoregulatory response in myofibroblast of a pediatric bladder inflammatory pseudotumor.

Inflammatory pseudotumor (IP) is generally considered to be a non-neoplastic, inflammatory response despite its gross and microscopic features of spindle cell neoplasm. Reported herein is a case arising from the muscularis propria of the urinary bladder in a 14-year-old girl who presented with gross hematuria and impending hypovolemic shock. The tumor consisted of proliferating myofibroblastic cells and various types of inflammatory cells. The immunoregulatory responses and reactions were investigated with regard to infiltration of inflammatory mononuclear cells being a documented finding in IP. Immunhistochemical and in situ hybridization studies for cytokines showed that the myofibroblastic cells were positive for interleukin (IL)-4, IL-5 and negative for interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha expression. The patient has been free of disease since excision of the tumor 34 months ago. Thus, cytokine production in IP suggests that it is reactive in nature and myofibroblasts may be the source of cytokines in the pathogenic process.