Most cases of type III hyperlipoproteinemia are accounted for by apolipoprotein E2 (apoE2) homozygotes, a genetic mutation of apoE (Arg158Cys). Glomerulopathy with homozygous apoE2 is rare and characterized by marked foam cell infiltration in the glomerular capillaries and mesangium. Here, we report 3 cases of apoE2 homozygote glomerulopathy diagnosed by renal biopsy and DNA analysis. All 3 cases were middle-aged or elderly males complicated with diabetes for at least a decade. The kidney biopsies showed massive foam cell infiltration in the glomerular capillaries and expanded mesangium accompanied by histological findings of diabetic glomerulosclerosis. The lipid profiles showed type III hyperlipoproteinemia and phenotypic/genetic analyses revealed homozygosity of apoE2. Two of the cases showed nephrotic proteinuria and progressed to renal failure in 3 and 8 years after the diagnosis of kidney disease.

ABSTRACT:Transplantation-associated thrombotic microangiopathy (TA-TMA) is relatively rare and requires immediate intervention to avoid irreversible organ damage or death; however, consensus regarding the treatment approach is lacking. Atypical haemolytic uraemic syndrome (aHUS) is a rare disease caused by dysregulation of the alternative complement pathway resulting in TMA. aHUS is histologically similar to TA-TMA; approximately 60% of TA-TMA patients have complement dysregulation. Eculizumab, a humanized anti-C5 monoclonal antibody, inhibits terminal membrane-attack complex formation and TMA progression. Eculizumab has been successfully used to treat aHUS posttransplant. We present two cases of kidney TA-TMA due to unknown causes, suspected antibody-mediated rejection, or calcineurin inhibitor (CNI)-related toxicity that developed on day 1 or 2 post-kidney transplantation. Low platelet count and haemoglobin level with red cell fragments were detected. Despite steroid pulse, plasma exchange (PE), and intravenous immunoglobulin therapy, TA-TMA did not improve; therefore, eculizumab was administered despite no genetic testing. Laboratory data, including renal function, improved immediately. TA-TMA treatment primarily involves PE initiation or CNI discontinuation; eculizumab can be used to safely treat TA-TMA and then be ceased in the short term. Therefore, eculizumab administration might be beneficial for kidney TA-TMA as early as the diagnosis of refractory to PE.

Millions worldwide suffer from incurable lung diseases, and organ transplantation remains their only hope. However, there has been an absolute shortage of donor lungs and unmet needs for transplantable lung generation composed of tissue-specific mesenchyme, epithelium, and endothelium. Elucidation of lung precursor traits during development can lead to solving this issue. Using lineage-tracing mice, we discovered that gastrulating Foxa2 lineage+ Pdgfrα+ mesendoderm forms the competitive mesenchymal lung niche. We further evidenced that Foxa2+Pdgfrα+ mesendoderm is an evolutionarily-conserved niche during human iPSC-derived lung differentiation. The Fgfr2 gene depletion, specifically in the Foxa2 lineage, showed lung agenesis phenotype. Strikingly, donor iPSCs injection into those blastocysts complemented endodermal and mesodermal defective lung organ niches that efficiently led to the entire lung generation. Together, targeting Foxa2 lineage for lung generation is a novel paradigm, holding a grand promise for future human whole lung generation in large animals using human iPSCs.

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BackgroundVancomycin is the first-line antibiotic for methicillin-resistant Staphylococcus aureus and coagulase-negative strains. The risk of vancomycin-induced acute kidney injury increases with plasma vancomycin levels. Vancomycin-induced acute kidney injury is histologically characterized by acute interstitial nephritis and/or acute tubular necrosis. However, only 12 biopsy-proven cases of vancomycin-induced acute kidney injury have been reported so far, as renal biopsy is rarely performed for such cases. Current recommendations for the prevention or treatment of vancomycin-induced acute kidney injury are drug monitoring of plasma vancomycin levels using trough level and drug withdrawal. Oral prednisone and high-flux haemodialysis have led to the successful recovery of renal function in some biopsy-proven cases.Case presentationWe present the case of a 41-year-old man with type 1 diabetes mellitus, who developed vancomycin-induced acute kidney injury during treatment for Fournier gangrene. His serum creatinine level increased to 1020.1 μmol/L from a baseline of 79.6 μmol/L, and his plasma trough level of vancomycin peaked at 80.48 μg/mL. Vancomycin discontinuation and frequent haemodialysis with high-flux membrane were immediately performed following diagnosis. Renal biopsy showed acute tubular necrosis and focal acute interstitial nephritis, mainly in the medullary rays (medullary ray injury). There was no sign of glomerulonephritis, but mild diabetic changes were detected. He was discharged without continuing haemodialysis (serum creatinine level, 145.0 μmol/L) 49 days after initial vancomycin administration.ConclusionsThis case suggests that frequent haemodialysis and renal biopsy could be useful for the treatment and assessment of vancomycin-induced acute kidney injury, particularly in high-risk cases or patients with other renal disorders.

Millions of people suffer from end-stage refractory diseases. The ideal treatment option for terminally ill patients is organ transplantation. However, donor organs are in absolute shortage, and sadly, most patients die while waiting for a donor organ. To date, no technology has achieved long-term sustainable patient-derived organ generation. In this regard, emerging technologies of chimeric human organ production via blastocyst complementation (BC) holds great promise. To take human organ generation via BC and transplantation to the next step, we reviewed current emerging organ generation technologies and the associated efficiency of chimera formation in human cells from the standpoint of developmental biology.

<b><i>Introduction:</i></b> Extra efferent arterioles, also known as polar vasculosis (PV), are often observed in the glomerular vascular pole and are associated with glomerular hypertrophy, indicating early recurrent diabetic kidney disease (DKD) in renal allografts. However, its significance in patients without diabetes remains uncertain. <b><i>Methods:</i></b> A total of 9,004 renal allograft biopsy specimens obtained between January 2007 and December 2017 at Tokyo Women’s Medical University were retrospectively analyzed to examine the clinical and pathological significance of PV in renal allografts. PV was identified in 186 biopsy specimens obtained from 165 patients. The PV group comprised 46 patients; 35 patients without DKD and 11 patients with DKD as the initial cause of ESRD, whose clinical information was available and treated with the calcineurin inhibitor (CNI) tacrolimus. The non-PV group comprising patients with renal allografts matched for age and postoperative day included 93 patients without DKD and 16 patients with DKD as the initial cause of ESRD. <b><i>Results:</i></b> In patients with nondiabetic renal allografts, systolic blood pressure was significantly higher in the PV group than in the non-PV group. The trough tacrolimus levels during the overall study period and at 2 weeks, 1 month, and 2 years after transplantation were significantly higher in the PV group compared with the non-PV group. Glomerulomegaly was significantly more common. Moreover, ah and aah scores in Banff score were significantly higher in the PV group than in the non-PV group. In those with diabetic renal allografts, although the clinical parameters and tacrolimus trough levels in all time periods were not significantly different between the PV and non-PV groups, the ah score was significantly higher in the PV group. <b><i>Conclusion:</i></b> PV was associated with CNI toxicity in nondiabetic but not in diabetic renal allografts. The pathogenesis of PV in renal allografts is considered to be multifactorial.

ABSTRACT:Immunoglobulin (Ig) A nephropathy (IgAN) is a known autoimmune disease due to abnormal glycosylation of IgA1, and occasionally, IgG co-deposition occurs. The prognosis of IgG co-deposition with IgAN is adverse, as shown in the previous studies. However, in the clinical setting, monoclonality of IgG codeposition with IgAN has not been observed. We describe a case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) combined with IgAN in a renal allograft. A-21-year-old man developed end-stage renal failure with unknown aetiology and underwent living-donor kidney transplantation from his mother 2 years after being diagnosed. One year after kidney transplantation, proteinuria 2+ and haematuria 2+ were detected; allograft biopsy revealed mesangial IgA and C3 deposits, indicating a diagnosis of IgAN. After tonsillectomy and steroid pulse therapy, proteinuria and haematuria resolved. However, 4 years after transplantation, pedal oedema, proteinuria (6.89 g/day) and allograft dysfunction (serum creatinine (sCr) 203.3 μmol/L) appeared. A second allograft biopsy showed mesangial expansion and focal segmental proliferative endocapillary lesions with IgA1λ and monoclonal IgG1κ depositions. Electron microscopic analysis revealed a massive amount of deposits, located in the mesangial and subendothelial lesions. A diagnosis of PGNMID complicated with IgAN was made, and rituximab and plasmapheresis were added to steroid pulse therapy. With this treatment, proteinuria was alleviated to 0.5 g/day, and the allograft dysfunction recovered to sCr 132.6 μmol/L. This case suggests a necessity for investigation of PGNMID and IgA nephropathy in renal allografts to detect monoclonal Ig deposition disease.Immunoglobulin (Ig) A nephropathy (IgAN) is the most common primary glomerular disease, and the incidence of recurrent IgAN is 50-60% in the 5 years after kidney transplantation. CASE REPORTA 21-year-old Japanese man was admitted to our hospital with exercise-induced dyspnoea and headache. The patient had