Successful treatment of a renal allograft abscess with antimicrobial agents alone and appropriate follow-up imaging.

A renal allograft abscess is a relatively rare condition. Appropriate antimicrobial therapy and drainage are recommended for treating renal abscesses. However, drainage can be challenging, depending on the location of the abscess. We present the case of a young female kidney transplant recipient who was successfully cured of a renal allograft abscess, using antimicrobial agents and appropriate follow-up imaging, without the need of any risky procedures.

Remarkable improvement of diabetic nephropathy in transplanted allograft after kidney transplantation.

Although glomerular damage caused by diabetic nephropathy was thought to be irre-versible, in recent years, there have been reports on improvement in glomerular damage with strict glycemic control. However, few reports are available on the pathologic course after renal transplantation of donor-derived grafts with findings of diabetic nephropathy. A 53-year-old woman underwent an ABO blood-type compatible living-donor renal transplant. The recipient had no history of diabetes, and fasting blood glucose and hemo-globin A1c (HbA1c) levels were both normal. The donor was a 57-year-old male who had received treatment for type 2 diabetes mellitus for 10 years. Transplant renal biopsy performed 1 h after revascularization showed mesangial matrix expansion and arterial hyalinosis due to diabetic nephropathy. The blood glucose level was within the normal range after transplantation. Mesangial matrix expansion and arterial hyalinosis disap-peared in allograft biopsy samples 7 years after transplantation. We observed significant improvement in the pathological findings of donor-derived diabetic nephropathy after renal transplantation in the subsequent follow-ups.

FGF21 and autophagy coordinately counteract kidney disease progression during aging and obesity.

Chronic kidney disease (CKD) has reached epidemic proportions worldwide, partly due to the increasing population of elderly and obesity. Macroautophagy/autophagy counteracts CKD progression, whereas autophagy is stagnated owing to lysosomal overburden during aging and obesity, which promotes CKD progression. Therefore, for preventing CKD progression during aging and obesity, it is important to elucidate the compensation mechanisms of autophagy stagnation. We recently showed that FGF21 (fibroblast growth factor 21), which is a prolongevity and metabolic hormone, is induced by autophagy deficiency in kidney proximal tubular epithelial cells (PTECs); however, its pathophysiological role remains uncertain. Here, we investigated the interplay between FGF21 and autophagy and the direct contribution of endogenous FGF21 in the kidney during aging and obesity using PTEC-specific fgf21- and/or atg5-deficient mice at 24 months (aged) or under high-fat diet (obese) conditions. PTEC-specific FGF21 deficiency in young mice increased autophagic flux due to increased demand of autophagy, whereas fgf21-deficient aged or obese mice exacerbated autophagy stagnation due to severer lysosomal overburden caused by aberrant autophagy. FGF21 was robustly induced by autophagy deficiency, and aged or obese PTEC-specific fgf21- and atg5-double deficient mice deteriorated renal histology compared with atg5-deficient mice. Mitochondrial function was severely disturbed concomitant with exacerbated oxidative stress and downregulated TFAM (transcription factor A, mitochondrial) in double-deficient mice. These results indicate that FGF21 is robustly induced by autophagy disturbance and protects against CKD progression during aging and obesity by alleviating autophagy stagnation and maintaining mitochondrial homeostasis, which will pave the way to a novel treatment for CKD.

A Case of Acute Kidney Injury Caused by Myoglobin Cast Nephropathy With Sars-Cov-2 Infection in a Living-Donor Kidney Transplant Recipient.

When COVID-19 affects patients with risk factors such as chronic kidney disease or on immunosuppressive drugs, they often rapidly become seriously ill. We describe a 50-year-old man who was affected with SARS-CoV-2 and had undergone an ABO-compatible living-donor kidney transplantation from his father 14 years ago because of end-stage renal failure due to hypertensive nephrosclerosis. He had continued on immunosuppressive drugs and completed vaccination twice (9 months ago and 6 months ago) with messenger RNA (mRNA) vaccines against SARS-CoV-2. However, he was temporarily on a mechanical ventilator due to respiratory failure and hemodialysis due to acute kidney injury (AKI). He was finally weaned from the ventilator and hemodialysis by taking steroid and antiviral drugs. Echo-guided renal biopsy revealed myoglobin cast nephropathy. We experienced 14 outpatients after living-donor kidney transplantation infected with SARS-CoV-2, but only this case developed AKI.

Diabetic nephropathy with marked extra-capillary cell proliferation: a case report.

BACKGROUND: Extra-capillary hypercellularity is a common finding in crescentic glomerulonephritis (GN) and focal segmental glomerulosclerosis (FSGS). In diabetic nephropathy (DN), extra-capillary hypercellularity is often observed as a finding of complications such as IgA nephropathy or microscopic polyangiitis superimposed on DN. However, in rare cases, epithelial cell proliferation may accompany DN. We experienced a case of nodular diabetic glomerulosclerosis with marked extra-capillary hypercellularity and revealed the origin of this atypical lesion using immunostainings. CASE PRESENTATION: A man in his 50 s was admitted to the hospital with nephrotic syndrome, and a renal biopsy was performed. Diffuse nodular lesions and extra-capillary hypercellularity were observed, but the results of serological examination or immunofluorescent assays did not implicate any other crescentic GN. Immunostaining for claudin-1 and nephrin was performed to identify the origin of the extra-capillary lesions. Given the clinical course and pathological findings, a diagnosis of DN-associated extra-capillary cell proliferation was made. CONCLUSIONS: Extra-capillary hypercellularity, which resembles FSGS or crescentic GN, is a rare finding in DN and should therefore be treated with caution. In such cases, co-staining for claudin-1 and nephrin may facilitate the diagnosis of DN.

A Case Report of a Kidney Transplant Recipient With Organizing Pneumonia After Graft Loss.

We present a case of a 68-year-old male patient who underwent ABO-incompatible living kidney transplantation from his wife because of immunoglobulin A nephropathy 13 years ago. Over time, the patient showed a gradual decline in graft function and required reinitiation of hemodialysis because of fluid overload, which led to his admission to our hospital. An arteriovenous fistula was created, and subsequently, hemodialysis therapy was started. Because he had chronic cytomegalovirus retinopathy and thrombotic microangiopathy due to immunosuppressive therapy at admission, mycophenolate mofetil and tacrolimus were discontinued during hemodialysis initiation. Only low-dose prednisolone was continued. One week later, the patient had a fever, and chest computed tomography revealed bilateral pneumonia, which was not improved by antibiotics. The patient was diagnosed with organized pneumonia. After ruling out opportunistic infection, including pneumocystis pneumonia, increased doses of prednisolone resulted in the remission of organizing pneumonia.

TFEB-mediated lysosomal exocytosis alleviates high-fat diet-induced lipotoxicity in the kidney.

Obesity is a major risk factor for end-stage kidney disease. We previously found that lysosomal dysfunction and impaired autophagic flux contribute to lipotoxicity in obesity-related kidney disease, in both humans and experimental animal models. However, the regulatory factors involved in countering renal lipotoxicity are largely unknown. Here, we found that palmitic acid strongly promoted dephosphorylation and nuclear translocation of transcription factor EB (TFEB) by inhibiting the mechanistic target of rapamycin kinase complex 1 pathway in a Rag GTPase-dependent manner, though these effects gradually diminished after extended treatment. We then investigated the role of TFEB in the pathogenesis of obesity-related kidney disease. Proximal tubular epithelial cell-specific (PTEC-specific) Tfeb-deficient mice fed a high-fat diet (HFD) exhibited greater phospholipid accumulation in enlarged lysosomes, which manifested as multilamellar bodies (MLBs). Activated TFEB mediated lysosomal exocytosis of phospholipids, which helped reduce MLB accumulation in PTECs. Furthermore, HFD-fed, PTEC-specific Tfeb-deficient mice showed autophagic stagnation and exacerbated injury upon renal ischemia/reperfusion. Finally, higher body mass index was associated with increased vacuolation and decreased nuclear TFEB in the proximal tubules of patients with chronic kidney disease. These results indicate a critical role of TFEB-mediated lysosomal exocytosis in counteracting renal lipotoxicity.

A heterozygous LAMA5 variant may contribute to slowly progressive, vinculin-enhanced familial FSGS and pulmonary defects.

The LAMA5 gene encodes laminin α5, an indispensable component of glomerular basement membrane and other types of basement membrane. A homozygous pathological variant in LAMA5 is known to cause a systemic developmental syndrome including glomerulopathy. However, the roles of heterozygous LAMA5 gene variants in human renal and systemic diseases have remained unclear. We performed whole-exome sequencing analyses of a family with slowly progressive nephropathy associated with hereditary focal segmental glomerulosclerosis, and we identified what we believe to be a novel probable pathogenic variant of LAMA5, NP_005551.3:p.Val3687Met. In vitro analyses revealed cell type-dependent changes in secretion of variant laminin α5 laminin globular 4-5 (LG4-5) domain. Heterozygous and homozygous knockin mice with a corresponding variant of human LAMA5, p.Val3687Met, developed focal segmental glomerulosclerosis-like pathology with reduced laminin α5 and increased glomerular vinculin levels, which suggested that impaired cell adhesion may underlie this glomerulopathy. We also identified pulmonary defects such as bronchial deformity and alveolar dilation. Reexaminations of the family revealed phenotypes compatible with reduced laminin α5 and increased vinculin levels in affected tissues. Thus, the heterozygous p.Val3687Met variant may cause a new syndromic nephropathy with focal segmental glomerulosclerosis through possibly defective secretion of laminin α5. Enhanced vinculin may be a useful disease marker.

Everolimus Reduces Cancer Incidence and Improves Patient and Graft Survival Rates after Kidney Transplantation: A Multi-Center Study.

Kidney transplantation can prevent renal failure and associated complications in patients with end-stage renal disease. Despite the good quality of life, de novo cancers after kidney transplantation are a major complication impacting survival and there is an urgent need to establish immunosuppressive protocols to prevent de novo cancers. We conducted a multi-center retrospective study of 2002 patients who underwent kidney transplantation between 1965 and 2020 to examine patient and graft survival rates and cumulative cancer incidence in the following groups categorized based on specific induction immunosuppressive therapies: group 1, antiproliferative agents and steroids; group 2, calcineurin inhibitors (CNIs), antiproliferative agents and steroids; group 3, CNIs, mycophenolate mofetil, and steroids; and group 4, mammalian target of rapamycin inhibitors including everolimus, CNIs, mycophenolate mofetil, and steroids. The patient and graft survival rates were significantly higher in groups 3 and 4. The cumulative cancer incidence rate significantly increased with the use of more potent immunosuppressants, and the time to develop cancer was shorter. Only one patient in group 4 developed de novo cancer. Potent immunosuppressants might improve graft survival rate while inducing de novo cancer after kidney transplantation. Our data also suggest that everolimus might suppress cancer development after kidney transplantation.

Incidence and mortality of post-transplant lymphoproliferative disorders after kidney transplantation: A real-world retrospective analysis in Japan.

OBJECTIVES: Post-transplant lymphoproliferative disorder is a potentially life-threatening complication that has a greater risk of occurrence in the setting of immunosuppression and oncogenic viral infections after transplant surgery. Few studies have reported the cumulative incidence, histological subtypes and clinical outcomes of this disorder in kidney transplant recipients. METHODS: We retrospectively investigated 34 post-transplant lymphoproliferative disorder patients diagnosed out of the 1210 kidney transplant recipients who had undergone the surgery at the two largest centers in Japan between January 1983 and December 2017. RESULTS: A total of 32 patients (94.1%) developed late-onset post-transplant lymphoproliferative disorder (diagnosed 1 year after transplantation). The cumulative incidence rates were 0.76% and 1.59% at 5 and 10 years post-transplantation, respectively. The central nervous system was the most common site (35.3%, 12/34). Overall survival was similar between patients with and without central nervous system lesions (P = 0.676). Of all of the cases, 23.5% (8/34) were detected through cancer screening. Importantly, patients with screening-detected post-transplant lymphoproliferative disorder had better overall survival than those with the disorder who had been symptom detected (P = 0.0215). Overall survival was significantly reduced in patients who developed the disorder compared with those who did not (P = 0.0001). CONCLUSIONS: Post-transplant lymphoproliferative disorder was more likely to occur in the late post-transplantation period, which showed that long-term medical examination for transplant recipients is required. Based on our findings, we propose vigilant, long-term, cancer screening in kidney transplant recipients.

Autopsy Findings of Heterozygous Fabry Disease with the Severe Phenotype: A Case Report.

Fabry disease (FD) is an inherited X-linked lysosomal storage disorder, with hemizygous males being more severely affected than heterozygous females. Herein, we report a rare case of FD in a heterozygous female with a severe phenotype. The patient had obesity and hyperlipidemia and had her first cerebral infarction at the age of 33 years. She underwent renal biopsy and was diagnosed with FD with morphological features of focal segmental glomerulosclerosis nephropathy at the age of 34 years. Her leukocyte alpha-galactosidase A activity was 2.3 Agal/U (normal: >20 Agal/U), and genetic analysis revealed the presence of the classical phenotype. Enzyme replacement therapy (ERT) was initiated at the age of 35 years; however, peritoneal dialysis owing to end-stage renal failure occurred at the age of 37 years. The patient died of a cerebral hemorrhage at the age of 44 years. Her Mainz Severity Score Index at the time of death was 48/76, suggestive of the severe phenotype. Autopsy findings revealed remarkable globotriaosylceramide accumulation on electron microscopy, particularly in the major organs and their vascular smooth muscle cells. Regarding the vertebral arteries which sourced the cerebral hemorrhage, the effects of FD-induced vascular thickening and long-term renal failure-induced atherosclerosis were confirmed. Furthermore, the patient's vascular sclerosis was modified with acquired factors such as lifestyle-related disease associated with obesity. We recommend intensified treatment for metabolic factors simultaneous with ERT to help in delaying the progression of FD.

Rapid deterioration of renal function following coronavirus disease 2019 in a renal transplant recipient.

Introduction: The coronavirus disease 2019 pandemic emerged in December 2019. Renal transplant recipients receiving chronic immunosuppression are considered to be at a high risk of infection. Aside from upper respiratory tract symptoms, coronavirus disease 2019 has also been reported to cause acute kidney injury in 20-50% of infected cases. Case presentation: A 62-year-old male renal transplant recipient presented with high fever, diarrhea, and cough, concurrent with rapid deterioration of graft function. The patient tested positive for coronavirus disease 2019. The pathological findings of the graft biopsy revealed diffuse flattening of tubular epithelial cells and extensive loss of the brush border in proximal tubular cells. Mycophenolate mofetil was discontinued and sotrovimab, remdesivir, intravenous immunoglobulin, and intravenous methylprednisolone were administered, resulting in gradual improvements in clinical symptoms and renal function. Conclusion: We describe a case of a coronavirus disease 2019-infected kidney transplant recipient who developed severe acute kidney injury caused by severe acute tubular necrosis.

Quantitative Analyses of Foot Processes, Mitochondria, and Basement Membranes by Structured Illumination Microscopy Using Elastica-Masson- and Periodic-Acid-Schiff-Stained Kidney Sections.

INTRODUCTION: Foot process effacement and mitochondrial fission associate with kidney disease pathogenesis. Electron microscopy is the gold-standard method for their visualization, but the observable area of electron microscopy is smaller than light microscopy. It is important to develop alternative ways to quantitatively evaluate these microstructural changes because the lesion site of renal diseases can be focal. METHODS: We analyzed elastica-Masson trichrome (EMT) and periodic acid-Schiff (PAS) stained kidney sections using structured illumination microscopy (SIM). RESULTS: EMT staining revealed three-dimensional (3D) structures of foot process, whereas ponceau xylidine acid fuchsin azophloxine solution induced fluorescence. Conversion of foot process images into their constituent frequencies by Fourier transform showed that the concentric square of (1/4)2-(1/16)2 in the power spectra (PS) included information for normal periodic structures of foot processes. Foot process integrity, assessed by PS, negatively correlated with proteinuria. EMT-stained sections revealed fragmented mitochondria in mice with mitochondrial injuries and patients with tubulointerstitial nephritis; Fourier transform quantified associated mitochondrial injury. Quantified mitochondrial damage in patients with immunoglobulin A (IgA) nephropathy predicted a decline in estimated glomerular filtration rate (eGFR) after kidney biopsy but did not correlate with eGFR at biopsy. PAS-stained sections, excited by a 640 nm laser, combined with the coefficient of variation values, quantified subtle changes in the basement membranes of patients with membranous nephropathy stage I. CONCLUSIONS: Kidney microstructures are quantified from sections prepared in clinical practice using SIM.

Cyclosporine A Treatment of Proteinuria in a New Case of MAFB-Associated Glomerulopathy without Extrarenal Involvement: A Case Report.

The MAFB gene encodes an important basic leucine zipper transcription factor that functions in glomerular podocytes, macrophages, and osteoclasts. Recently, MAFB was identified as the gene that was responsible for causing nephropathy with focal segmental glomerulosclerosis (FSGS) with multicentric carpotarsal osteolysis (MCTO) or Duane retraction syndrome (DRS). Here, we describe a patient with nephropathy associated with FSGS who exhibited a novel stop-gain variant in the MAFB gene (NM_005461:c.590C>A (p.Ser197Ter)). The patient's father exhibited proteinuria with FSGS with possible DRS, whereas the patient exhibited nephropathy with FSGS and nearly normal eye movement and hearing function, as well as intact bone structure in the extremities. Conventional oral steroids or immunosuppressive drugs have not demonstrated effectiveness for patients with nephropathy who exhibit pathogenic variants in MAFB, except for a patient with nephropathy with FSGS and MCTO who experienced attenuated proteinuria within the subnephrotic range in response to cyclosporine A (CyA) treatment for at least 4 years. Thus, we attempted administration of CyA in our patient. Unexpectedly, the patient demonstrated good and rapid responses to CyA, including a partial reduction in proteinuria from approximately 2.0 g/g Cr to proteinuria within the subnephrotic range (0.27 g/g Cr) after 13 months of observation. Our findings suggest that CyA may be a suitable treatment option for patients with nephropathy with FSGS who exhibit pathogenic MAFB variants.

The effect of cholecalciferol supplementation on allograft function in incident kidney transplant recipients: A randomized controlled study.

It is unknown whether cholecalciferol supplementation improves allograft outcomes in kidney transplant recipients (KTRs). We conducted a single-center randomized, double-blind, placebo-controlled trial of daily 4000 IU cholecalciferol supplementation in KTRs at 1-month posttransplant. The primary endpoint was the change in eGFR from baseline to 12-month posttransplant. Secondary endpoints included severity of interstitial fibrosis and tubular atrophy (IFTA) at 12-month posttransplant and changes in urinary biomarkers. Of 193 randomized patients, 180 participants completed the study. Changes in eGFR were 1.2 mL/min/1.73 m2 (95% CI; -0.7 to 3.1) in the cholecalciferol group and 1.8 mL/min/1.73 m2 (95% CI, -0.02 to 3.7) in the placebo group, with no significant between-group difference (-0.7 mL/min/1.73 m2 [95% CI; -3.3 to 2.0], p = 0.63). Subgroup analyses showed detrimental effects of cholecalciferol in patients with eGFR <45 mL/min/1.73 m2 (Pinteraction <0.05, between-group difference; -4.3 mL/min/1.73 m2 [95% CI; -7.3 to -1.3]). The degree of IFTA, changes in urine albumin-to-creatinine ratio, or adverse events including hypercalcemia and infections requiring hospitalization did not differ between groups. In conclusion, cholecalciferol supplementation did not affect eGFR change compared to placebo among incident KTRs. These findings do not support cholecalciferol supplementation for improving allograft function in incident KTRs. Clinical trial registry: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as UMIN000020597 (please refer to the links below). UMIN-CTR: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023776.

Eicosapentaenoic acid attenuates renal lipotoxicity by restoring autophagic flux.

Recently, we identified a novel mechanism of lipotoxicity in the kidney proximal tubular cells (PTECs); lipid overload stimulates macroautophagy/autophagy for the renovation of plasma and organelle membranes to maintain the integrity of the PTECs. However, this autophagic activation places a burden on the lysosomal system, leading to a downstream suppression of autophagy, which manifests as phospholipid accumulation and inadequate acidification in lysosomes. Here, we investigated whether pharmacological correction by eicosapentaenoic acid (EPA) supplementation could restore autophagic flux and alleviate renal lipotoxicity. EPA supplementation to high-fat diet (HFD)-fed mice reduced several hallmarks of lipotoxicity in the PTECs, such as phospholipid accumulation in the lysosome, mitochondrial dysfunction, inflammation, and fibrosis. In addition to improving the metabolic syndrome, EPA alleviated renal lipotoxicity via several mechanisms. EPA supplementation to HFD-fed mice or the isolated PTECs cultured in palmitic acid (PA) restored lysosomal function with significant improvements in the autophagic flux. The PA-induced redistribution of phospholipids from cellular membranes into lysosomes and the HFD-induced accumulation of SQSTM1/p62 (sequestosome 1), an autophagy substrate, during the temporal and genetic ablation of autophagy were significantly reduced by EPA, indicating that EPA attenuated the HFD-mediated increases in autophagy demand. Moreover, a fatty acid pulse-chase assay revealed that EPA promoted lipid droplet (LD) formation and transfer from LDs to the mitochondria for beta-oxidation. Noteworthy, the efficacy of EPA on lipotoxicity is autophagy-dependent and cell-intrinsic. In conclusion, EPA counteracts lipotoxicity in the proximal tubule by alleviating autophagic numbness, making it potentially suitable as a novel treatment for obesity-related kidney diseases.Abbreviations: 4-HNE: 4-hydroxy-2-nonenal; ACTB: actin beta; ADGRE1/F4/80: adhesion G protein-coupled receptor E1; ATG: autophagy-related; ATP: adenosine triphosphate; BODIPY: boron-dipyrromethene; BSA: bovine serum albumin; cKO: conditional knockout; CML: N-carboxymethyllysine; COL1A1: collagen type I alpha 1 chain; COX: cytochrome c oxidase; CTRL: control; DGAT: diacylglycerol O-acyltransferase; EPA: eicosapentaenoic acid; FA: fatty acid; FFA: free fatty acid; GFP: green fluorescent protein; HFD: high-fat diet; iKO: inducible knockout; IRI: ischemia-reperfusion injury; LAMP1: lysosomal-associated membrane protein 1; LD: lipid droplet; LRP2: low density lipoprotein receptor-related protein 2; MAP1LC3: microtubule-associated protein 1 light chain 3; MTORC1: mechanistic target of rapamycin kinase complex 1; OA: oleic acid; PAS: periodic-acid Schiff; PPAR: peroxisome proliferator activated receptor; PPARGC1/PGC1: peroxisome proliferator activated receptor, gamma, coactivator 1; PTEC: proximal tubular epithelial cell; ROS: reactive oxygen species; RPS6: ribosomal protein S6; SDH: succinate dehydrogenase complex; SFC/MS/MS: supercritical fluid chromatography triple quadrupole mass spectrometry; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; TG: triglyceride; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling.

Urinary mulberry bodies as a potential biomarker for early diagnosis and efficacy assessment of enzyme replacement therapy in Fabry nephropathy.

BACKGROUND: The inability of enzyme replacement therapy (ERT) to prevent progression of Fabry nephropathy (FN) in the presence of >1 g/day proteinuria underscores the necessity of identifying effective biomarkers for early diagnosis of FN preceding proteinuria. Here we attempted to identify biomarkers for early detection of FN. METHODS: Fifty-one Fabry disease (FD) patients were enrolled. Urinary mulberry bodies (uMBs) were immunostained for globotriaosylceramide (Gb3) and renal cell markers to determine their origin. The association between semiquantitative uMB excretion and the histological severity of podocyte vacuolation was investigated in seven patients using the vacuolated podocyte:glomerular average area ratio. The association between the semiquantitative estimate of uMB excretion and duration of ERT was analyzed. A longitudinal study was conducted to assess the effect of ERT on uMB excretion. RESULTS: Thirty-two patients (63%) had uMBs, while only 31% showed proteinuria. The uMBs were positive for Gb3, lysosomal-associated membrane protein 1 and podocalyxin, suggesting they were derived from lysosomes with Gb3 accumulation in podocytes. We observed more severe podocyte vacuolation with increased uMB excretion (P = 0.03 for trend); however, the same was not observed with increased proteinuria. The percentage of patients with substantial uMB excretion increased with shorter ERT duration (P = 0.018). Eighteen-month-long ERT reduced uMB excretion (P = 0.03) without affecting proteinuria. CONCLUSIONS: uMB excretion, implying ongoing podocyte injury, preceded proteinuria in most patients. Semiquantitative uMB estimates can serve as novel biomarkers for early FN diagnosis and for monitoring the efficacy of FD-specific therapies.

Increased vascular permeability and severe renal tubular damage after ischemia-reperfusion injury in mice lacking adiponectin or T-cadherin.

Adiponectin (APN) is a circulating protein specifically produced by adipocytes. Native APN specifically binds to T-cadherin, a glycosylphosphatidylinositol-anchored protein, mediating the exosome-stimulating effects of APN in endothelial, muscle, and mesenchymal stem cells. It was previously reported that APN has beneficial effects on kidney diseases, but the role of T-cadherin has not been clarified yet. Here, our immunofluorescence study indicated the existence of both T-cadherin and APN protein in pericytes, subsets of tissue-resident mesenchymal stem/progenitor cells positive for platelet-derived growth factor receptor ß (PDGFRß), surrounding peritubular capillaries. In an acute renal ischemia-reperfusion (I/R) model, T-cadherin-knockout (Tcad-KO) mice, similar to APN-KO mice, exhibited the more progressive phenotype of renal tubular damage and increased vascular permeability than wild-type mice. In addition, in response to I/R-injury, the renal PDGFRß-positive cell area increased in wild-type mice, but opposingly decreased in both Tcad-KO and APN-KO mice, suggesting severe pericyte loss. Mouse primary pericytes also expressed T-cadherin. APN promoted exosome secretion in a T-cadherin-dependent manner. Such exosome production from pericytes may play an important role in maintaining the capillary network and APN-mediated inhibition of renal tubular injury. In summary, our study suggested that APN protected the kidney in an acute renal injury model by binding to T-cadherin.NEW & NOTEWORTHY In the kidney, T-cadherin-associated adiponectin protein existed on peritubular capillary pericytes. In an acute renal ischemia-reperfusion model, deficiency of adiponectin or T-cadherin exhibited the more progressive phenotype of renal tubular damage and increased vascular permeability, accompanied by severe pericyte loss. In vitro, adiponectin promoted exosome secretion from mouse primary pericytes in a T-cadherin-dependent manner. Adiponectin plays an important role in maintaining the capillary network and amelioration of renal tubular injury by binding to T-cadherin.

Recurrence of Proliferative Glomerulonephritis with Monoclonal Immunoglobulin G Deposits with a Striated Ultrastructure.

A 64-year-old man with nephrotic syndrome was admitted to another hospital where his renal biopsy revealed membranoproliferative glomerulonephritis (MPGN) with monoclonal immunoglobulin (Ig) G, subclass 1, κ light chain (IgG1κ) deposition on immunofluorescence (IF). Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) was suspected due to monoclonal IgG1κ deposits and the absence of hematological abnormalities. However, the typical PGNMID phenotype was not observed by electron microscopy. Instead, an organized and striated muscle-like structure was observed in the subendothelial space. Since a 2-year treatment with immunosuppressants did not improve his proteinuria, a second biopsy was performed at our hospital. It showed an MPGN-like phenotype; however, monoclonal Ig deposits on IF were no longer observed. One year after the second biopsy, he developed ESRD. Thus, he underwent living kidney transplantation from his wife. Allograft biopsy was performed as proteinuria was observed 3 months after transplantation, which again showed an MPGN-like phenotype with monoclonal IgG1κ deposits. The observed electron-dense deposits were similar to those in the native biopsies. Accordingly, the patient was diagnosed with recurrent MPGN. Adding methylprednisolone pulse therapy to conventional immunosuppressants did not improve the patient's renal function or proteinuria. He died of Legionella pneumonia 8 months after transplantation. Considering the patient's histological findings of MPGN with monoclonal IgG1κ deposits and early recurrence of glomerulonephritis after transplantation, he was diagnosed with PGNMID with novel electron-dense deposits.