BACKGROUND: Acute kidney injury (AKI) is a critical condition with a complex aetiology and different outcomes, where haemodynamic dysfunction, renal hypoperfusion and inflammation serve as key contributors to its development and progression. Early and accurate diagnosis is vital for initiating targeted treatments like fluid resuscitation, vasoactive agents or steroid therapy, which are essential for improving patient outcomes. Intravoxel incoherent motion (IVIM) MRI assesses both capillary perfusion and tissue water diffusion, while arterial spin labelling (ASL) MRI measures renal blood flow without the need for contrast. Research on combined use of IVIM and ASL MRI in patients with AKI is rare. This study aims to investigate the MRI characteristics of IVIM and ASL in patients with tubulointerstitial nephritis (TIN) and to explore their relationship with pathological findings and renal recovery.
METHODS: Single-centre, prospective, observational cohort study of 30 patients with biopsy-proven TIN. Participants will undergo renal IVIM and ASL MRI within 7 days post-biopsy. The pathological assessments of active and chronic tubulointerstitial injuries will be semiscored using modified Banff criteria. The estimated glomerular filtration rate (eGFR) during follow-up and prevalence of chronic kidney disease at 3 and 6 months will be reported. An eGFR below 45 mL/min is considered a poor renal outcome.
BACKGROUND: The study has been reviewed and approved by the Ethics Committee of Peking University First Hospital and written informed consent will be obtained from all participants (2022Y503). The study results will be disseminated through publication in a relevant peer-reviewed journal and presentation at academic meetings to increase awareness and share findings with the scientific community.

BACKGROUND: Vancomycin, a commonly prescribed antibiotic particularly in the setting of multi-drug resistant infections, is limited by its nephrotoxicity. Despite its common occurrence, much remains unknown on the clinicopathologic profile as well as the pathogenesis of vancomycin nephrotoxicity. Clinical studies included patients often with severe comorbidities and concomitant polypharmacy confounding the causal pathogenesis. Animal models cannot recapitulate this complex clinical situation. Kidney biopsy was not commonly performed.
METHODS: To address this limitation, we studied 36 patients who had renal biopsies for acute kidney injury (AKI) for suspicion of vancomycin nephrotoxicity. Detailed renal biopsy evaluation, meticulous evaluation of clinical profiles, and up-to-date follow-up allowed for a diagnostic categorization of vancomycin nephrotoxicity (VNT) in 25 patients and absence of vancomycin nephrotoxicity (NO-VNT) in 11 patients. For careful comparison of these two groups, we proceeded to compile a clinicopathologic and morphologic profiles characteristic for each group.
RESULTS: Patients with VNT had a characteristic clinical profile including a common clinical background, a high serum trough level of vancomycin, a rapidly developed and severe acute kidney injury, and a recovery of renal function often shortly after discontinuation of vancomycin. This clinical course was correlated with characteristic renal biopsy findings including acute tubulointerstitial nephritis of allergic type, frequent granulomatous inflammation, concomitant and pronounced acute tubular necrosis of nephrotoxic type, and vancomycin casts, in the absence of significant tubular atrophy and interstitial fibrosis. This clinico-pathologic profile was different from that of patients with NO-VNT, highlighting its role in the diagnosis, management and pathogenetic exploration of vancomycin nephrotoxicity.
CONCLUSIONS: Vancomycin nephrotoxicity has a distinctive morphologic and clinical profile, which should facilitate diagnosis, guide treatment and prognostication, and confer pathogenetic insights.

BACKGROUND: BK polyomavirus (BKPyV) infection after kidney transplantation can lead to serious complications such as BKPyV-associated nephropathy (BKPyVAN) and graft loss. The aim of this study was to investigate the incidence of BKPyVAN after implementing a BKPyV screening program, to map the distribution of BKPyV genotypes and subtypes in the Uppsala-Örebro region and to identify host and viral risk factors for clinically significant events.
METHODS: This single-center prospective cohort study included kidney transplant patients aged ≥ 18 years at the Uppsala University Hospital in Sweden between 2016 and 2018. BKPyV DNA was analyzed in plasma and urine every 3 months until 18 months after transplantation. Also genotype and subtype were determined. A logistic regression model was used to analyze selected risk factors including recipient sex and age, AB0 incompatibility and rejection treatment prior to BKPyVAN or high-level BKPyV DNAemia.
RESULTS: In total, 205 patients were included. Of these, 151 (73.7%) followed the screening protocol with 6 plasma samples, while184 (89.8%) were sampled at least 5 times. Ten (4.9%) patients developed biopsy confirmed BKPyVAN and 33 (16.1%) patients met criteria for high-level BKPyV DNAemia. Male sex (OR 2.85, p = 0.025) and age (OR 1.03 per year, p = 0.020) were identified as significant risk factors for developing BKPyVAN or high-level BKPyV DNAemia. BKPyVAN was associated with increased viral load at 3 months post transplantation (82,000 vs. < 400 copies/mL; p = 0.0029) and with transient, high-level DNAemia (n = 7 (27%); p < 0.0001). The most common genotypes were subtype Ib2 (n = 50 (65.8%)) and IVc2 (n = 20 (26.3%)).
CONCLUSIONS: Male sex and increasing age are related to an increased risk of BKPyVAN or high-level BKPyV DNAemia. BKPyVAN is associated with transient, high-level DNAemia but no differences related to viral genotype were detected.

OBJECTIVE: We investigated the efficacy of a predetermined protocol that consisted of immunosuppressive drug reduction/withdrawal and intravenous immunoglobulin administration for the treatment of polyoma BK virus nephropathy.
METHODS: Patients with biopsy-proven polyoma BK virus nephropathy received a treatment regimen based on discontinuation of both calcineurin inhibitors and antiproliferative agents and switching to mTOR inhibitors accompanied by intravenous immunoglobulin administration.
RESULTS: Our study included 508 patients, with polyoma BK viremia detected in 80 patients. The mean age was 45.3 ± 9.5 years (range, 18-71 y), 64% were male, and mean follow-up was 37 ± 21 months (6-94 mo). All 16 patients who developed polyoma BK virus nephropathy and 9 patients who had highgrade polyoma BK viremia without nephropathy received intravenous immunoglobulin treatment. Compared with patients with viremia, patients with polyoma BK virus nephropathy had significantly higher rates of graft loss due to rejection (18.8% vs 1.6%; P = .024) and all-cause graft loss (31.2% vs 6.3%; P = .014). Histopathologically, viral inclusion bodies disappeared and SV40 became negative after treatment in all 13 patients who underwent protocol biopsies. Unfortunately, histopathologically complete recovery without chronic tubular and interstitial tissue damage was achieved in only 4 patients after treatment. In addition, 3 patients lost their grafts due to acute antibody-mediated or mixed-type rejection (18.8%).
CONCLUSIONS: In patients with polyoma BK virus nephropathy, clearance of viremia and SV40 should not be the sole outcomes to obtain. Aggressive reductions in maintenance immunosuppression and switching to double-drug therapy combined with high-dose intravenous immunoglobulin leads to high rates of graft loss/rejection and sequalae of chronic histological changes.

The interplay between gut microbiome genera and inflammatory kidney-related diseases, such as nephrotic syndrome, glomerulonephritis, tubulo-interstitial nephritis, and chronic kidney disease, has been observed. However, the causal relationships between specific bacterial genera and these renal diseases have not been fully elucidated.
To investigate the potential causal links between different genera of the gut microbiome and the susceptibility to various renal conditions utilizing two-sample Mendelian randomization (MR) analyses.
Genome-wide association study (GWAS) summary statistics of gut microbiota and inflammatory kidney-related diseases were obtained from published GWASs. Two-sample MR analyses were conducted using methods including inverse-variance weighted (IVW), MR Egger, and others to identify potential causal links between gut microbial genera and renal conditions. Sensitivity analyses, including Cochran\'s Q test and the MR-PRESSO global test, were performed to validate the robustness of the results and detect horizontal pleiotropy. In addition, a reverse MR analysis was conducted to assess reverse causation possibilities.
By synthesizing insights from both primary and sensitivity analyses, this study unveiled critical associations of 12 bacterial genera with nephrotic syndrome, 7 bacterial genera with membranous nephropathy, 3 bacterial genera with glomerulonephritis, 4 bacterial genera with acute tubulo-interstitial nephritis, 6 bacterial genera with chronic tubulo-interstitial nephritis, and 7 bacterial genera with chronic kidney disease. Various genera were pinpointed as having either positive or negative causal relationships with these renal conditions, as evidenced by specific ranges of IVW-OR values (all P< 0.05). The congruence of the sensitivity analyses bolstered the primary findings, displaying no marked heterogeneity or horizontal pleiotropy. Notably, the reverse MR analysis with nephritis as the exposure did not reveal any causal relationships, thereby strengthening the resilience and validity of the primary associations.
This study explored the causal associations between several gut microbial genera and the risk of several inflammatory kidney-related diseases, uncovering several associations between specific gut microbial genera and nephrotic syndrome, membranous nephropathy, glomerulonephritis, tubulo-interstitial nephritis, and chronic kidney disease. These findings enhance our understanding of the complex interplay between the gut microbiome and kidney diseases, and they will be beneficial for early diagnosis and subsequent treatment.

BACKGROUND: Acute tubulointerstitial nephritis (ATIN) is a well-recognized cause of acute kidney injury (AKI) due to the tubulointerstitial inflammation. The aim of this study was to explore the clinical features, outcomes, and responses to corticosteroid treatment in patients with ATIN.
METHODS: Patients with biopsy-proven ATIN, who were diagnosed between 1994 and 2016 at the Department of Nephrology, Charles University, First Faculty of Medicine, and General University Hospital in Prague, were included in the study. Patient demographics, the aetiological and clinical features, the treatment given, and the outcome at 1 year of follow-up were extracted from patient records.
RESULTS: A total of 103 ATIN patients were analysed, of which 68 had been treated with corticosteroids. There was no significant difference in the median serum creatinine 280 (169-569) µmol/L in the conservatively managed group versus 374 (249-558) µmol/L in the corticosteroid-treated group, p = 0.18, and dependence on dialysis treatment at baseline at the time of biopsy (10.3 vs. 8.6%). During the 1 year of follow-up, those ATIN patients who had been treated with corticosteroids did better and showed greater improvement in kidney function, determined as serum creatinine difference from baseline and from 1 month over 1-year period (p = 0.001).
CONCLUSIONS: This single-centre retrospective cohort study supports the beneficial role of the administration of corticosteroid therapy in the management of ATIN.

Nephropathy due to BK virus infection is a major cause of graft dysfunction and loss. No specific treatment has been developed for the BK virus. Here, we compared the combination of intravenous immunoglobulin and leflunomide versus intravenous immunoglobulin to treat BK virus nephropathy after renal transplant.
This study was a randomized controlled clinical trial. Sixteen kidney transplant patients with BK virus infection were randomly divided into 2 groups; 1 group received intravenous immunoglobulin, and another group received leflunomide and intravenous immunoglobulin. P < .05 was considered statistically significant.
Results of a polymerase chain reaction test for BK virus after 2 months of treatment were negative in 3 patients in the intravenous immunoglobulin group and in 7 patients in the intravenous immunoglobulin + leflunomide group. The amount of BK virus decreased significantly in each group, and a significant difference was observed between the 2 groups after 3 months (P = .014). The average level of creatinine in the intravenous immunoglobulin group at 1, 2, and 3 months after treatment was 1.7 ± 0.23, 1.8 ± 0.5, and 1.5 ± 0.3, respectively, and in the intravenous immunoglobulin + leflunomide group was 2.1 ± 0.75, 1.76 ± 0.37, and 1.4 ± 0.18, respectively (P > .05).
Although BK viral load decreased significantly in both groups, there was a significant difference between patients who received intravenous immunoglobulin versus those who received the combination of intravenous immunoglobulin + leflunomide after 3 months. The addition of leflunomide to the intravenous immunoglobulin treatment seems to have a better effect in reducing BK viral load. However, further studies with a larger sample and longer duration are needed.

UNASSIGNED: East-European data on cancer in patients undergoing hemodialysis (HD) are scarce. This study aimed to assess the pattern of cancer and related mortality in patients with end-stage kidney disease (ESKD) undergoing HD.
UNASSIGNED: Retrospectively analyzing data from 7 HD centers, this study examined 1377 incident HD patients divided into three groups: no-cancers (NoC), cancers that occurred prior to HD initiation (CPI) and de novo cancer developed after HD initiation (DNC). Mortality risk and survival trends within groups were analyzed using Cox regression and Kaplan-Meier methods.
UNASSIGNED: In the cohort, 89.46% of the patients had no cancer (NoC group), 3.63% had cancer before (CPI group), and 6.89% had cancer after HD initiation (DNC group). The mean time from HD initiation to DNC diagnosis was 1 [2.75] years. Older age was associated with a higher risk of developing DNC (p < 0.001). Chronic tubulointerstitial nephritis (CTIN) is more prevalent in cancer patients. The most common cancer sites among DNC patients were the digestive (29.47%) and urinary tracts (18.95%), while those in CPI subjects were hematologic (22%) and digestive (20%). Cancer was an independent predictor of mortality risk (HR = 6.9, 95% [CI]:4.5-10.6, p < 0.001).
UNASSIGNED: East-European ESKD patients undergoing HD have a high incidence of de novo cancers whose primary cancer sites are the digestive and urinary tracts. Almost half of the HD patients with CPI have hematologic and digestive tract cancers. Age and CTIN were associated with cancer risk. Cancer is an independent risk factor for all-cause mortality in patients undergoing hemodialysis (HD).

Sarcoidosis is characterized by noncaseating granulomatous inflammation in multiple organs. Renal involvement is rare, and granulomatous interstitial nephritis (GIN) is the predominant histological feature. Renal sarcoidosis (RS) is usually diagnosed by exclusion, combining clinical and histological findings, and often remains misdiagnosed. This retrospective study aimed to describe the characteristics and prognosis of patients with RS in China.
Eighteen patients with RS from a single center were enrolled, of whom 15 had biopsy-proven tubulointerstitial nephritis. Their clinicopathological features and renal outcomes were analyzed to understand this rare disease better.
Eighteen patients (14 male/4 female) were included in our study. The median estimated glomerular filtration rate (eGFR) was 30.36 (11.57, 60.14) mL/min/1.73 m2. In 15 patients undergoing a renal biopsy, GIN was the most common pathological phenotype (66.67%). Seventeen patients had follow-up records, with a median follow-up of 24.07 (8.82, 60.90) months. One month after treatment, median eGFR increased significantly from 30.36 (11.57, 60.14) mL/min/1.73 m2 to 58.53 (39.35, 80.65) mL/min/1.73 m2, and proteinuria decreased from 1.10 (0.69, 1.58) g/24 h to 0.68 (0.52, 1.05) g/24 h. No patients relapsed or developed end-stage renal disease.
RS is a rare but important cause of tubulointerstitial injury, with a favorable long-term prognosis if properly diagnosed and treated promptly.

Polymorphisms of HLA genes may confer susceptibility to acute tubulointerstitial nephritis (ATIN), but small sample sizes and candidate gene design have hindered their investigation. The first genome-wide association study of ATIN identified two significant loci, risk haplotype DRB1*14-DQA1*0101-DQB1*0503 (DR14 serotype) and protective haplotype DRB1*1501-DQA1*0102-DQB1*0602 (DR15 serotype), with amino acid position 60 in the peptide-binding groove P10 of HLA-DR β 1 key. Risk alleles were shared among different causes of ATIN and HLA genotypes associated with kidney injury and immune therapy response. HLA alleles showed the strongest association. The findings suggest that a genetically conferred risk of immune dysregulation is part of the pathogenesis of ATIN.
Acute tubulointerstitial nephritis (ATIN) is a rare immune-related disease, accounting for approximately 10% of patients with unexplained AKI. Previous elucidation of the relationship between genetic factors that contribute to its pathogenesis was hampered because of small sample sizes and candidate gene design.
We undertook the first two-stage genome-wide association study and meta-analysis involving 544 kidney biopsy-defined patients with ATIN and 2346 controls of Chinese ancestry. We conducted statistical fine-mapping analysis, provided functional annotations of significant variants, estimated single nucleotide polymorphism (SNP)-based heritability, and checked genotype and subphenotype correlations.
Two genome-wide significant loci, rs35087390 of HLA-DQA1 ( P =3.01×10 -39 ) on 6p21.32 and rs2417771 of PLEKHA5 on 12p12.3 ( P =2.14×10 -8 ), emerged from the analysis. HLA imputation using two reference panels suggested that HLA-DRB1*14 mainly drives the HLA risk association . HLA-DRB1 residue 60 belonging to pocket P10 was the key amino acid position. The SNP-based heritability estimates with and without the HLA locus were 20.43% and 10.35%, respectively. Different clinical subphenotypes (drug-related or tubulointerstitial nephritis and uveitis syndrome) seemed to share the same risk alleles. However, the HLA risk genotype was associated with disease severity and response rate to immunosuppressive therapy.
We identified two candidate genome regions associated with susceptibility to ATIN. The findings suggest that a genetically conferred risk of immune dysregulation is involved in the pathogenesis of ATIN.