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Anemia and vitamin D deficiency are associated with allograft failure, and hence, are potential therapeutic targets among kidney transplant recipients (KTRs). We conducted a multicenter, two-by-two factorial, open-label, randomized clinical trial to examine the effects of anemia correction and vitamin D supplementation on 2-year change in eGFR among KTRs (CANDLE-KIT). We enrolled 153 patients with anemia and >1-year history of transplantation across 23 facilities in Japan, and randomly assigned them to either a high or low hemoglobin target (>12.5 vs. <10.5 g/dl) and to either cholecalciferol 1000 IU/day or control. This trial was terminated early based on the planned interim intention-to-treat analyses (α = 0.034). Among 125 patients who completed the study, 2-year decline in eGFR was smaller in the high vs. low hemoglobin group (i.e., -1.6 ± 4.5 vs. -4.0 ± 6.9 ml/min/1.73 m 2 ; P = 0.021), but did not differ between the cholecalciferol and control groups. These findings were supported by the fully adjusted mixed effects model evaluating the rate of eGFR decline among all 153 participants. There were no significant between-group differences in all-cause death or the renal composite outcome in either arm. In conclusion, aggressive anemia correction showed a potential to preserve allograft kidney function., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Non-immune injury leading to interstitial fibrosis and tubular atrophy (IF/TA) in renal allografts has various etiologies, but pathological means of verification have yet to be developed. Medullary ray injury (MRI) is a pathological feature of many non-immune injuries inducing IF/TA and pathological determination of calcineurin inhibitor (CNI) toxicity proceeding to striped fibrosis. We investigated the contribution of CNI toxicity to MRI and other non-immune etiologies related to IF/TA. In this study MRI is defined as fibrosis and inflammation localized exclusively to the medullary ray. Thirty-six protocol biopsies showing MRI were analyzed and classified histopathologically as following: MRI related to CNI toxicity; chronic obstruction or reflux nephropathy; and acute or chronic pyelonephritis. The etiology of MRI was CNI toxicity (n= 16, 44.4%), chronic obstruction (n= 13, 36.1%), acute or chronic pyelonephritis (n= 2, 5.6%), and other (n= 5, 13.9%). We performed cystography in seven cases of MRI related to chronic obstruction or reflux nephropathy and six cases showing vesicoureteral reflux. The ci+ct score showed significant progression after one year in 30 of the 36 cases (1.53 ± 1.04 vs. 3.03 ± 1.13, P < 0.01). MRI has various etiologies and may also predict changes in urological complications. The classification of MRI may be useful to determine the non-immune etiology leading to IF/TA., (© 2010 The Authors. Pathology International © 2010 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.)

Thyroidization (thyroid-like appearance) in renal tissue which is made up of a colloid-like hyaline cast formation of Tamm-Horsfall glycoprotein (THP) is a common finding in chronic pyelonephritis and obstructive nephropathy. This type of pathological change is sometimes observed in renal allograft specimens. We examined allograft specimens for thyroidization and other pathological findings related to thyroidization to characterize the conditions causing such changes. One-hundred three patients who underwent renal transplantation between January 2006 and April 2008 at Gifu University Hospital (251 renal allograft biopsy specimens) were enrolled in this study. Sixteen patients had thyroidization (11 mild, 4 moderate, and 1 severe). In four patients, THP reflux on Bowman's capsule was found, and in three patients interstitial THP deposits were observed. In four patients, tubulointerstitial nephritis was diagnosed. Fifteen of 16 patients were examined for vesicoureteral reflux (VUR) with voiding cystourethrography. Three of 15 patients had VUR. In the past medical histories of the 16 patients with thyroidization, three had low capacity bladders, two had prostate diseases, and six had previous urinary tract infections. In cases of thyroidization with additional findings, including THP reflux into Bowman's space and interstitial THP deposits, we need to examine the patients for the presence of urinary tract diseases. In cases of thyroidization and tubulointerstitial nephritis urinary tract infections were suspected. Such subclinical urological diseases in the grafts might affect the prognosis of renal function. Therefore, appropriate management of urinary tract diseases is required.

Dense deposit disease (DDD), also known as type II membranoproliferative glomerulonephritis (MPGN), is characterized by the presence of continuous intramembranous dense deposits. At present, the histogenesis of DDD is not well known. Reported herein are two cases of early recurrence of DDD in renal allografts, with marked endocapillary proliferation. In case 1 the first allograft biopsy revealed electron-dense deposits mainly in the subendothelial and mesangial areas along with subepithelial humps, but a continuous intramembranous deposition was not obvious. In the sequential biopsy, the deposits were more often seen in the intramembranous area and finally formed a continuous osmiophilic substance, which is a characteristic feature of DDD. In case 2, continuous intramembranous deposition already coexisted with endocapillary proliferation at the first biopsy. In both cases, endocapillary proliferation was alleviated slightly as time progressed. The present report suggests that endocapillary proliferative glomerulonephritis is the earliest lesion in some cases of DDD. Detailed review of a clinical history and a subsequent follow-up biopsy should be done to distinguish these lesions from other types of endocapillary proliferative glomerulonephritis.