Transplant glomerulopathy (TG) is a prominent feature of chronic rejection that is characterized by double contours of the glomerular capillaries (GC). In this report, we demonstrate that one of the histopathological features of TG is a phenotypic change of glomerular endothelial cells which is illustrated by increased caveolae formation. To verify the endothelial changes in this disease, we examined the expression of plasmalemmal vesicle‐associated protein‐1 (PV‐1), a glycoprotein associated with plasmalemmal vesicles (caveolae), in the glomeruli of TG patients using pathologische anatomie Leiden‐endothelium (PAL‐E) antibody. Twenty‐six cases of chronic allograft nephropathy (CAN) with TG were examined, compared with 16 cases of CAN without TG, type I MPGN (4 cases), and transplant glomerulitis (8 cases). Overall, 24 of 26 (92.3%), 4 of 16 (25%), 0 of 4, 0 of 8 cases were PAL‐E‐positive for GC, respectively. Further, the extent of glomerular PAL‐E expression was positively correlated with both the grade of TG (rs= 0.72, p = 0.0003) and proteinuria (g/day) (rs= 0.51, p = 0.02). A correlation was not observed between glomerular PAL‐E positivity and peritubular capillary C4d deposits (Yetes chi = 0.23, p = 0.89). In summary, the present study demonstrates expression of PV‐1 in the GC of TG which is correlated with the grade of TG and proteinuria.

Improvements in immunosuppression have reduced acute kidney allograft rejection and clinicians are now seeking ways to prolong allograft survival to 20 years and beyond. The primary cause of kidney allograft loss is still chronic rejection, followed by death with a functioning allograft and primary kidney disease recurrence. Thus, overcoming kidney allograft rejection remains the most important issue. Kidney allograft rejection can be classified into two types: T cell- and antibody-mediated rejection. Both are diagnosed pathologically based on the Banff 2013 classification. Other important pathological features in addition to rejection include calcineurin inhibitor toxicity, polyomavirus nephropathy, and recurrence of the primary kidney disease. Here, we review the diagnosis and representative features of histopathological findings in transplanted kidneys.

Background: Recurrence of IgA nephropathy (IgAN) in the transplanted kidney is associated with graft survival, but no specific treatment is available. Tonsillectomy (TE) reportedly arrests the progression of IgAN in the native kidney. Thus, we conducted a single-center retrospective cohort study to evaluate the effect of TE prior to IgAN recurrence.

Peritubular capillary basement membrane multilayering (PTCBMML) is a pathological landmark of chronic rejection‐induced transplant capillaropathy (TC), but its cellular mechanisms are not fully understood. We observed de novo caveolae formation in endothelial cells in TC under electron microscopy. To examine the role of caveolae and their structural components in TC, biopsy samples from cases of chronic rejection were double‐immunostained for Caveolin‐1 (Cav‐1) and Pathologische Anatomie Leiden‐endothelium (PAL‐E; a marker of peritubular capillary [PC]). Thirty‐two cases of chronic rejection (group I) were compared with 18 cases of interstitial fibrosis and tubular atrophy with no evidence of any specific etiology (IF/TA; group II) and eight cases of peritubular capillaritis (group III). The Cav‐1/PAL‐E immunoreactivities in groups I–III (%Cav‐1/PAL‐E) were 41.8±23.1%, 8.1±7.3% (p < 0.01 vs. group I) and 12.7±7.4% (p < 0.01 vs. group I), respectively. Furthermore, multiple linear regression models demonstrated that %Cav‐1/PAL‐E was independently associated with the PTCBMML grade and reduced PC number. No correlation was observed between %Cav‐1/PAL‐E and PC C4d deposition in group I. We conclude that de novo caveolae formation in PC endothelia is involved in TC in chronic rejection.

High protein intake can increase glomerular filtration rate (GFR) in response to excretory overload, which may exacerbate the progression of kidney disease. However, the direct association between glomerular hemodynamic response at the single-nephron level and dietary protein intake has not been fully elucidated in humans. In the present study, we evaluated nutritional indices associated with single-nephron GFR (SNGFR) calculated based on corrected creatinine clearance (SNGFR_Cr). We retrospectively identified 43 living kidney donors who underwent enhanced computed tomography and kidney biopsy at the time of donation at Jikei University Hospital in Tokyo from 2007 to 2018. Total nephron number was estimated with imaging-derived cortical volume and morphometry-derived glomerular density. SNGFR_Cr was calculated by dividing the corrected creatinine clearance by the number of non-sclerosed glomeruli (Nglom_NSG). The mean (± standard deviation) Nglom_NSG/kidney and SNGFR_Cr were 685,000 ± 242,000 and 61.0 ± 23.9 nL/min, respectively. SNGFR_Cr was directly associated with estimated protein intake/ideal body weight (p = 0.005) but not with body mass index, mean arterial pressure, albumin, or sodium intake. These findings indicate that greater protein intake may increase SNGFR and lead to glomerular hyperfiltration.

IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. IgAN progresses to end-stage kidney disease in 20–40% of patients within 20 years of diagnosis. Kidney transplantation is the most effective option for patients with end-stage kidney disease caused by IgAN, but recurrence can occur in the transplanted kidney. The IgAN recurrence rate varies from 1% to 10% per year and varies according to the follow-up period, diagnostic modality, and biopsy criteria. Of note, studies based on protocol biopsies have reported a higher incidence of recurrence, which also occurred earlier after transplantation. In addition, recent data show that recurrence of IgAN is a more significant cause of allograft failure than previously believed. Little is known about the pathophysiology of IgAN recurrence, but several potential biomarkers have been investigated. Among them, galactose-deficient IgA1 (Gd-IgA1), IgG anti-Gd-IgA1 antibodies, and soluble CD89 could play a pivotal role in disease activity. This review aims to describe the current status of recurrent IgAN, including the incidence, clinical characteristics, risk factors, and future perspectives, with a focus on the available therapeutic approaches.