Extracellular Vesicle Therapeutics in Regenerative Medicine.

Extracellular vesicles (EVs) are nano-sized, cell-released vesicles which contain lipids, proteins, and nucleic acids derived from the parental cells. EVs play an important role in intercellular communication and influence both physiological and pathological conditions. They are increasingly explored as potential therapeutic agents since they can cross biological barriers, their cargo is protected from degradation and they are involved in the transfer of bioactive components.

Rapidly progressive glomerulonephritis caused by tegafur/gimeracil/oteracil resulted in diabetes nephropathy, in a patient with minor risk of diabetes nephropathy: a case report.

A 79-year-old Japanese male with a history of type 2 diabetes mellitus (T2DM) for 16 years was admitted to evaluate possible renal disease. The T2DM was well controlled in this patient using nutrition therapy without the need for any diabetes medication, and both diabetes retinopathy and proteinuria were negative. At the age of 78 advanced colorectal cancer (stage IIIa) was diagnosed and laparoscopic-assisted colectomy was performed.

How to resolve confusion in the clinical setting for the diagnosis of heterozygous COL4A3 or COL4A4 gene variants? Discussion and suggestions from nephrologists.

Both thin basement membrane nephropathy (TBMN) and autosomal dominant Alport syndrome (ADAS) are types of hereditary nephritis resulting from heterozygous mutations in COL4A3 or COL4A4 genes. Although TBMN is characterized by hematuria and thinning of the glomerular basement membrane (GBM) with excellent renal prognosis, some patients develop end-stage renal disease (ESRD) later in life. In contrast, although AS is characterized by progressive nephropathy with lamellation of the GBM, there are some patients diagnosed with ADAS from a family history of ESRD but who only suffer from hematuria with GBM thinning.

Correction to: Isolation and Characterization of Extracellular Vesicles from Keratinocyte Cultures.

The original version of this chapter was inadvertently published with incorrect spelling of surname of the authors. The names should read Sebastian Sjöqvist, Aya Imafuku, Danu Gupta, and Samir EL Andaloussi, and not Sebastian Sjöqvist, Aya Imafuku, Dhanu Ghupta, and Samir E. L.

Rat Mesenchymal Stromal Cell Sheets Suppress Renal Fibrosis via Microvascular Protection.

Renal fibrosis is one of the largest global health care problems, and microvascular (MV) injury is important in the development of progressive fibrosis. Although conventional cell therapy suppresses kidney injury via the role of vasoprotective cytokines, the effects are limited due to low retention of administered cells. We recently described that transplantation of hepatocyte growth factor (HGF)-transgenic mesothelial cell sheets showed a remarkable cell survival and strong therapeutic effects in a rat renal fibrosis model.

Isolation and Characterization of Extracellular Vesicles from Keratinocyte Cultures.

Extracellular vesicles (EVs), including exosomes, are nano-sized membrane-bound particles which are released by cells. They have been found in all examined body fluids and can be isolated from conditioned cell culture media. These vesicles have gained increasing attention due to their importance in cellular cross talk, in both health and disease.

Significance of urinary albumin excretion in patients with cast nephropathy .

Background: This study was performed to determine whether the urinary albumin excretion rate (%UAE) could distinguish myeloma cast nephropathy (MCN) without glomerular amyloid deposition from MCN with glomerular amyloid deposition.

Materials And Methods: We retrospectively reviewed clinicopathological data on 16 patients with MCN diagnosed by renal biopsy at Toranomon Hospital from 2004 to 2014.

Results: A total of 10 patients had pure MCN without glomerular amyloid deposition (group 1), and 6 patients had MCN with glomerular amyloid deposition (group 2).

Exosomes derived from clinical-grade oral mucosal epithelial cell sheets promote wound healing.

The oral mucosa exhibits unique regenerative properties, sometimes referred to as foetal-like wound healing. Researchers from our institute have used sheets of oral mucosa epithelial cells (OMECs) for regenerative medicine applications including cornea replacement and oesophageal epithelial regeneration for stricture prevention. Here, we have isolated exosomes from clinical-grade production of OMEC sheets from healthy human donors ( = 8), aiming to evaluate the clinical potential of the exosomes to stimulate epithelial regeneration and to improve understanding of the mode-of-action of the cells.

Incidence and risk factors of new-onset hypertrophic pachymeningitis in patients with anti-neutrophil antibody-associated vasculitis: using logistic regression and classification tree analysis.

Objectives: Hypertrophic pachymeningitis (HP) is a rare complication in patients with anti-neutrophil antibody-associated vasculitis (AAV); its clinical features, incidence, and risk factors remain unknown. We aimed to clarify the prevalence, clinical features, and factors associated with new-onset HP in patients with AAV.

Method: A retrospective cohort study involving 93 patients with AAV was conducted.

Acute Kidney Injury by Renal Hemosiderosis Secondary to Primary Cold Agglutinin Disease Associated with an Excessive Alcohol Intake.

Renal hemosiderosis occurs in the context of severe intravascular hemolysis, with the most common cause being paroxysmal nocturnal hematuria. Patients with cold agglutinin disease (CAD) have relatively mild hemolysis, and acute kidney injury (AKI) due to renal hemosiderosis has not been reported. We encountered a patient with CAD caused by lymphoplasmacytic lymphoma who developed AKI secondary to renal hemosiderosis after an excessive alcohol intake.

Detection of Splicing Abnormalities and Genotype-Phenotype Correlation in X-linked Alport Syndrome.

Background: X-linked Alport syndrome (XLAS) is a progressive hereditary nephropathy caused by mutations in the gene. Genotype-phenotype correlation in male XLAS is relatively well established; relative to truncating mutations, nontruncating mutations exhibit milder phenotypes. However, transcript comparison between XLAS cases with splicing abnormalities that result in a premature stop codon and those with nontruncating splicing abnormalities has not been reported, mainly because transcript analysis is not routinely conducted in patients with XLAS.

Primary Central Nervous System Post-transplant Lymphoproliferative Disorder Diagnosed by Peripheral Facial Nerve Palsy.

Although primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) causes various symptoms depending on the tumor region, there has been no previous report of PCNS-PTLD in the cerebellopontine angle that was diagnosed due to peripheral facial nerve palsy. We herein report a case involving a 62-year-old man with PCNS-PTLD in the cerebellopontine angle who was diagnosed due to peripheral facial nerve palsy. The reduction of immunosuppressive therapy, whole-brain radiotherapy, intrathecal chemotherapy, and rituximab were effective in treating this patient.

Risk factors of ceftriaxone-associated biliary pseudolithiasis in adults: influence of renal dysfunction.

Background: Ceftriaxone (CTRX) is a known cause of biliary pseudolithiasis (BPL) mainly in children. Biliary elimination of CTRX increases in patients with renal dysfunction. However, the influence of renal dysfunction on the incidence of CTRX-associated BPL has not been well investigated.

Autosomal dominant form of type IV collagen nephropathy exists among patients with hereditary nephritis difficult to diagnose clinicopathologically.

Aim: Type IV collagen nephropathies include Alport Syndrome and thin basement membrane nephropathy (TBMN), which are caused by mutations in COL4A3/A4/A5 genes. Recently, reports of patients with heterozygous mutations in COL4A3/A4 have been increasing. The clinical course of these patients has a wide variety, and they are diagnosed as TBMN, autosomal dominant Alport syndrome (ADAS), or familial focal segmental glomerular sclerosis.

Multicentric Castleman's disease associated with IgA vasculitis (Henoch-Schönlein purpura) responding well to tocilizumab: a case report.

A 41-year-old man was referred to our hospital for the evaluation of hypergammaglobulinemia (IgG 2898 mg/dL and IgA 587 mg/dL), inflammation (CRP 6.7 mg/dL and serum interleukin-6 (IL-6) 15.1 ng/L), and anemia (Hb 10.

Intracystic magnetic resonance imaging in patients with autosomal dominant polycystic kidney disease: features of severe cyst infection in a case-control study.

Background: The purpose of this study was to investigate the usefulness of intracystic MRI features for detection of severe cyst infection that is usually refractory to antibiotic therapy alone in patients with autosomal dominant polycystic kidney disease.

Methods: Seventy-six patients (88 episodes) with positive cyst cultures treated from January 2006 to December 2013 were enrolled as the cases for this case-control study, while 147 patients who continued to attend our hospital from January 2011 to December 2013 and did not have cyst infection diagnosed during that period were enrolled as the controls. Intracystic MRI findings were investigated.

Bone Histology of Two Cases with Osteomalacia Related to Low-dose Adefovir.

We performed a bone histomorphometric analysis in two patients demonstrating Fanconi syndrome with hypophosphatemia, adefovir-related bone disease and chronic hepatitis B infection. Both patients had osteomalacia, but showed two different histological patterns. The osteoid volume of the patient without risedronate increased with [(osteoid volume/ bone volume)×100=18.

Recurrent Cholangitis in a Patient with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and Caroli's Disease.

We herein present a rare case of an autosomal dominant polycystic kidney disease (ADPKD) patient with Caroli's disease, a congenital embryonic biliary tree ductal plate abnormality often associated with autosomal recessive polycystic kidney disease. A 76-year-old woman with ADPKD on hemodialysis was admitted to our hospital with recurrent cholangitis and hepatobiliary stones. Caroli's disease was diagnosed according to typical imaging findings of cystic intrahepatic bile duct dilatation and the central dot sign.

AA-negative and Kappa-positive Amyloidosis in a Patient with Rheumatoid Arthritis.

A 57-year-old Japanese woman with a 5-year history of rheumatoid arthritis (RA) was admitted to our hospital for an evaluation of nephrotic range proteinuria (4.8 g/day). A renal biopsy led to the diagnosis of amyloidosis according to strong positivity for Congo red staining and the detection of microfibrillar structures on electron microscopy that were negative for AA and positive for kappa light chain.

Acquired hemophilia A that developed during the induction of hemodialysis: the use of double-filtration plasmapheresis .

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies to coagulation factor VIII (FVIII). AHA onset during the induction of dialysis is extremely rare, and the management of blood access is difficult. We present a case of AHA that developed during induction of dialysis and treatment with double filtration plasmapheresis (DFPP).

A clinical staging score to measure the severity of dialysis-related amyloidosis.

Background: The ongoing effort to prevent dialysis-related amyloidosis (DRA) has been hampered by lack of any way to measure DRA's severity. Yet, such measurement is essential for assessing the effect of DRA treatment. Accordingly, we developed a scoring system focused on the physical manifestations of DRA.

Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport Syndrome.

Background And Objectives: Alport syndrome comprises a group of inherited heterogeneous disorders involving CKD, hearing loss, and ocular abnormalities. Autosomal dominant Alport syndrome caused by heterozygous mutations in collagen 4A3 and/or collagen 4A4 accounts for <5% of patients. However, the clinical, genetic, and pathologic backgrounds of patients with autosomal dominant Alport syndrome remain unclear.

Clinicopathological analysis of allogeneic hematopoietic stem cell transplantation-related membranous glomerulonephritis.

Allogeneic hematopoietic stem cell transplantation (HSCT)-related membranous glomerulonephritis (MGN) is poorly understood. A total of 830 patients who underwent HSCT at Toranomon Hospital from 2000 to 2012 were evaluated retrospectively, including 621 patients receiving umbilical cord blood transplantation (UCBT) and 208 patients receiving unrelated bone marrow transplantation. MGN was diagnosed in 5 patients after UCBT (versus none after bone marrow transplantation) and occurred concomitantly with chronic graft-versus-host disease after cessation of immunosuppression.

Effect of Proteinuria and Glomerular Filtration Rate on Renal Outcome in Patients with Biopsy-Proven Benign Nephrosclerosis.

Background: Reduced estimated glomerular filtration rate (eGFR) and proteinuria are risk factors for end-stage renal disease (ESRD), of which benign nephrosclerosis is a common cause. However, few biopsy-based studies have assessed these associations.

Methods: We performed retrospective cohort study of 182 Japanese patients who underwent renal biopsy from June 1985 through March 2014 and who were diagnosed with benign nephrosclerosis.

Suitability of Patients with Autosomal Dominant Polycystic Kidney Disease for Renal Transcatheter Arterial Embolization.

In patients with autosomal dominant polycystic kidney disease (ADPKD), massive renal enlargement is a serious problem. Renal transcatheter arterial embolization (TAE) can reduce renal volume (RV), but effectiveness varies widely, and the reasons remain unclear. We investigated factors affecting renal volume reduction rate (RVRR) after renal TAE in all 449 patients with ADPKD who received renal TAE at Toranomon Hospital from January of 2006 to July of 2013, including 228 men and 221 women (mean age =57.