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Objective To investigate the influence of transient receptor potential cation channel 6 (TRPC6) on renal tubulointerstitial inflammation in mice with diabetic kidney disease (DKD) and its mechanism. Methods A total of 36 male C57/BL6J mice, aged 6 weeks, were randomly divided into control group (group A), DKD model group (group B), DKD+normal saline intervention group (group C), DKD+mitophagy activator intervention group (group D), DKD+negative control lentivirus transfection group (group E), and DKD+TRPC6 knockdown lentivirus transfection group (group F), with 6 mice in each group. The mice in groups A and B were respectively given intraperitoneal injection of 0.1 mmol/L citrate buffer and 10 g/L streptozotocin (hereinafter referred to as administration); the mice in groups C and D were respectively given normal saline and 10 mmol/L urolithin A by gavage in addition to the treatment in group B; the mice in groups E and F were respectively injected with negative control lentivirus and TRPC6 knockdown lentivirus via the tail vein in addition to the treatment in group B. The levels of fasting blood glucose (FBG), urinary albumin-to-creatinine ratio (ACR), and blood urea nitrogen (BUN) were measured at week 12 after administration; PAS staining was used for the observation and scoring of renal tubular injury; RT-qPCR was used to measure the mRNA expression levels of inflammatory factors [interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α)] in renal tissue; immunohistochemical staining was used to measure the protein expression level of TRPC6 in renal tissue, and Western blotting was used to measure the relative expression levels of TRPC6, LC3B, P62, PINK1, and Parkin in renal tissue; transmission electron microscopy was used to observe the change in the number of mitophagosomes in renal tubular cells of mice. HK-2 cells were divided into high glucose+TRPC6 siRNA transfection+DMSO intervention group (group G, treated with TRPC6 siRNA+35.0 mmol/L glucose+0.06% DMSO) and high glucose+TRPC6 siRNA transfection+mitophagy inhibitor intervention group (group H, treated with TRPC6 siRNA+35.0 mmol/L glucose+12 μmol/L oroxylin A), and then RT-qPCR was used to measure the mRNA expression levels of inflammatory factors (IL-1β, MCP-1, and TNF-α) in cells. Results At week 12 after administration, compared with group A, group B had significantly higher whole blood FBG, ACR, BUN, renal tubular injury score, mRNA expression levels of inflammatory factors, and protein expression levels of TRPC6 and P62 in renal tissue (t=2.77-13.61,P

Acute interstitial nephritis (AIN) is a complication of drugs that may cause permanent kidney injury. AIN has been reported in patients with inflammatory bowel disease (IBD) treated with the integrin inhibitor vedolizumab. Through systematic review of existing literature, we aimed to identify and describe cases of AIN in patients with IBD treated with vedolizumab. We searched Medline, Embase, Cochrane, and Web of Science Core Collection between 1 January 2009 and 25 April 2023. The search yielded 1473 publications. Titles and abstracts were screened by two independent reviewers. Seventy publications were reviewed in full-text. Eight met the inclusion criteria. Clinical characteristics of AIN cases were extracted. Case causality assessment was performed according to two international adverse drug reaction probability assessment scales. Results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Nine biopsy-confirmed cases of AIN were reported in six patients with ulcerative colitis and three with Crohn's disease. Mean age at AIN onset was 36 years (range = 19–58) and the majority of patients were females (n = 6/9). Time from vedolizumab treatment initiation to AIN onset spanned from hours to 12 months. Common symptoms were fever and malaise. Creatinine levels were elevated in all patients. Five patients sustained permanent kidney injury. Our findings suggest that vedolizumab, although rarely, could cause AIN in patients with IBD. Awareness of laboratory findings and symptoms consistent with AIN, along with monitoring of the kidney function, could be warranted in patients with IBD treated with vedolizumab. [ABSTRACT FROM AUTHOR]

Macrophages are important cells involved in inflammatory damage in chronic kidney disease. The characteristic alteration of macrophage function due to changes in the local microenvironment is referred to as macrophage reprogramming. In recent years, altered macrophage reprogramming affecting inflammatory tissue injury has received increasing attention. This article reviews advances in the understanding of macrophage metabolic reprogramming pathways and studies that influence macrophage polarization and impact inflammatory injury in chronic kidney disease.

Background: Lithium is considered the gold standard for the treatment of bipolar affective disorder for the prevention of recurrence of manic and depressive episodes and for augmentation treatment in unipolar severe depressive episodes. The indications for treatment with lithium do not differ for older or younger patients. Nevertheless, there are a number of aspects to be considered with respect to drug safety in the group of old patients. Objective: The aim was to give an overview of the current literature on lithium treatment in old age and from this to derive recommendations for action. Material and methods: A selective literature review on lithium treatment in old age was conducted to answer questions on drug safety, monitoring (particularly with respect to comorbidities) and potential alternatives to lithium. Results and discussion: Lithium is an effective and, if used correctly, safe drug also in old people; however, with respect to somatic comorbidities that increase with age, special caution is required when using lithium in order to prevent nephropathy and intoxication. [ABSTRACT FROM AUTHOR]

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Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction. Tubulointerstitial nephritis and uveitis syndrome is a rare oculo-renal disease characterized by the presence of bilateral, anterior uveitis and tubulointerstitial nephritis. The pathogenesis of this disease is still not completely clear. It is associated with prior drug use, infections and autoimmune diseases. The involvement of the cellular and humoral immune responses and genetic predisposition to the development of this syndrome are frequently mentioned in the literature. In a certain number of cases, despite extensive diagnostics, the cause remains unknown (idiopathic tubulointerstitial nephritis and uveitis syndrome). Case Report. A fifteen-year-old female patient was admitted to the Department of Nephrology due to complaints of headache in the temples that occasionally occurred in the previous months. Three days before admission, the patient presented with symptoms of upper respiratory tract infection and subfebrile temperature (to 37.8°C). Laboratory test results revealed the development of acute tubulointerstitial nephritis, and in the fifth week of the disease, bilateral anterior uveitis was detected. The diagnosis was confirmed by percutaneous kidney biopsy. Systemic and local corticosteroid therapy was introduced, and after a month it resulted in gradual normalization of kidney function, proteinuria reduction and withdrawal of the ophthalmic symptoms. Conclusion. Due to the fact that kidney damage is often self-limited and that uveitis tends to be recurrent, there is a high probability of untimely diagnosis. Early recognition, detection of potential causes and initiation of treatment, are crucial in the prevention of disease progression and development of chronic sequelae such as chronic renal failure and chronic uveitis. [ABSTRACT FROM AUTHOR]

Introduction: We report a case study of two male pediatric patients presenting with anterior uveitis and elevated renal function parameters. Both were diagnosed with tubulointerstitial nephritis and uveitis syndrome and subsequently developed diffuse cerebral symptoms such as headache, fatigue, and diziness., Methods: Magnetic resonance images (MRIs) of the brain showed T2-hyperintense lesions with and without gadolinium enhancement leading to brain biopsy and diagnosis of small-vessel central nervous system (CNS) vasculitis in both cases. Both patients were treated according to BrainWorks small-vessel vasculitis protocol and symptoms vanished over the course of treatment. Follow-up MRIs up to 12 months after initiation of therapy showed no signs of recurrence indicating a monophasic disease., Conclusion: Small-vessel CNS vasculitis can occur simultaneously to other autoimmune diseases (ADs) in the scope of polyautoimmunity. As clinical findings of CNS vasculitis are often unspecific, neurological symptoms in nonneurological ADs should be adressed thoroughly. Under suspicion of small-vessel CNS vasculitis brain biopsy is still the gold standard and only secure way of definitive diagnosis., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: 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 and Analysis: 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., Ethics and Dissemination: 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Introduction: 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., Conclusion: Vancomycin nephrotoxicity has a distinctive morphologic and clinical profile, which should facilitate diagnosis, guide treatment and prognostication, and confer pathogenetic insights., Competing Interests: The authors declare that no competing interests exist., (Copyright: © 2024 Nachiappa Ganesh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: BK viremia after kidney transplantation (KT) poses significant risk for BK virus-associated nephropathy and impacts graft survival. Conventional treatment involves reduction of immunosuppression, which in turn may increase risk for rejection. To address this dilemma, use of anti-viral therapy with immunosuppressive properties such as leflunomide is an attractive option., Methods: We performed a multi-center, retrospective chart review to report tolerability and effectiveness of leflunomide use for the eradication of BK viremia and prevention of BK virus-associated nephropathy in pediatric KT recipients., Results: Seventy patients prescribed leflunomide were included and were followed up from initiation until 1 year following leflunomide completion. BK viremia was eradicated in 64 (91.4%) patients including 8 of 11 with nephropathy (BKVN) on initial biopsy. Reduced anti-proliferative medication (AP) dosing was not associated with increase in biopsy proven rejection (BPAR). However, complete discontinuation of AP during leflunomide therapy was associated with increase in BPAR in uni- and multivariate logistic regression, as was targeted reduction in calcineurin inhibitor (CNI) trough goals. One graft was lost to BKVN. There was no significant association found between time to BK eradication and leflunomide trough concentration, mycophenolate dose reduction, or steroid use (univariate logistic regression). Few leflunomide adverse drug reactions (ADR) were reported (most commonly: gastrointestinal, hematologic)., Conclusion: Leflunomide is a promising adjunctive treatment to immunosuppression reduction for BK virus eradication with minimal ADR. AP reduction, not discontinuation, and judicious reduction in CNI trough goals with close monitoring, is a promising strategy for treatment of BK viremia with concomitant use of leflunomide therapy., (© 2024 Wiley Periodicals LLC.)

Approximately 1% of all patients with Sjögren's syndrome (SS) are children. Unlike the adult form, in which sicca syndrome is the main presentation, in children, the most common clinical finding is recurrent enlargement of the salivary glands. In pediatric SS, extraglandular manifestations represent a significant feature and, among these, kidney manifestations are relevant. Kidney involvement is observed in 5-20.5% of children with SS, most frequently tubulointerstitial nephritis. This injury can lead to serious phenotypes, including distal kidney tubular acidosis with the development of severe hypokalemia, which can lead to ECG abnormalities, weakness, and hypokalemic periodic paralysis. Kidney implications in pediatric SS also include nephrolithiasis, nephrocalcinosis, and various types of glomerular damage, which often require immunosuppressive therapies. Laboratory findings are usually comparable to adults, including hyperglobulinemia and high rates of antinuclear antibodies (ANA, 63.6-96.2%), and anti-Ro/SSA (36.4-84.6%). The current classification criteria for SS are inaccurate for the pediatric population, and more specific criteria are needed to improve the diagnostic rate. Due to the rarity of the disease, strong recommendations for treatment are lacking, and several therapeutic strategies have been reported, mostly based on glucocorticoids and disease-modifying antirheumatic drugs, with different outcomes. The aim of this paper is to provide an overview of the kidney implications of pediatric SS based on the latest evidence of the medical literature., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Abstract Background Tubulo-interstitial Nephritis and Uveitis (TINU) syndrome is a rare oculo-renal inflammatory disease. Renal tubular defects are usually found, but full proximal tubular abnormalities have rarely been described. Case presentation We report the case of a 55-year old woman, native from Morocco, presenting with bilateral, non-granulomatous, anterior uveitis, mild renal insufficiency, leucocyturia and glycosuria. Further work-up showed hypophosphatemia and hyperphosphaturia, hypouricemia and hyperuricosuria, and hyper aminoaciduria, consistent with Fanconi syndrome. A kidney biopsy was obtained and showed diffuse interstitial infiltrates with tubular necrosis. The patient improved after the initiation of a corticosteroid therapy, with tapering dose. Conclusions We reviewed the literature and found nine similar cases. This association mostly occurs in adult woman, without current evidence for an ethnic predilection, unlike previously reported. The renal prognosis seems favorable after corticosteroid therapy, even in case of severe renal injury. Nonetheless mild tubular defects may persist after treatment or spontaneous remission.

Objectives: To report the ocular findings, laboratory results, and management of patients with tubulointerstitial nephritis and uveitis syndrome (TINU), whose numbers increased during the 2019 coronavirus disease (COVID-19) pandemic., Materials and Methods: Demographic characteristics, ophthalmic examination findings, laboratory results including polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), serum SARS-CoV-2 immunoglobulin G (IgG) antibody, and treatment of patients diagnosed with TINU between March 2020 and March 2022 were evaluated retrospectively., Results: The study included 19 eyes of 10 patients (6 female/4 male). The mean age was 13.5±2.4 years (range: 8-16 years). The mean follow-up duration was 13.5±6.1 months (range: 6-24 months). All patients presented with anterior uveitis. Anterior uveitis was bilateral in 9 patients (90%) and unilateral in 1 patient (10%). Posterior segment findings were normal in 8 patients (80%), and bilateral optic disc edema was observed in only 2 patients (20%). None of the patients had a previous SARS-CoV-2 infection and/or vaccination history. The SARS-CoV-2 PCR test was negative in all patients at presentation. The SARS-CoV-2 IgG antibody test was reactive in 7 patients (70%). Recurrent uveitis developed in 8 patients (80%) during follow-up. Systemic immunomodulatory therapy was required for the control of ocular inflammation in 7 patients (70%) with severe uveitis flare-ups., Conclusion: TINU is a multisystemic autoimmune disease, especially in response to environmental triggering factors such as viral infections. Although TINU is a rare disease, the number of cases increased during the COVID-19 pandemic. SARS-CoV-2 antibodies were detected at a significant rate of 70% in these patients, who did not have a history of SARS-CoV-2 infection and vaccination. Previous asymptomatic SARS-CoV-2 infection in children may be a triggering factor in the development of TINU., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2024 by the Turkish Ophthalmological Association / Turkish Journal of Ophthalmology published by Galenos Publishing House.)

Background: 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., Objective: 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., Materials and Methods: 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., Results: 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., Conclusion: 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Feng, Zhang, Lai, Jia, Wu and Chen.)

Diabetic nephropathy (DN) is the primary complication of diabetes mellitus. Ferroptosis is a form of cell death that plays an important role in DN tubulointerstitial injury, but the specific molecular mechanism remains unclear. Here, we downloaded the DN tubulointerstitial datasets GSE104954 and GSE30529 from the Gene Expression Omnibus database. We examined the differentially expressed genes (DEGs) between DN patients and healthy controls, and 36 ferroptosis-related DEGs were selected. Pathway-enrichment analyses showed that many of these genes are involved in metabolic pathways, phosphoinositide 3-kinase/Akt signaling, and hypoxia-inducible factor-1 signaling. Ten of the 36 ferroptosis-related DEGs (CD44, PTEN, CDKN1A, DPP4, DUSP1, CYBB, DDIT3, ALOX5, VEGFA, and NCF2) were identified as key genes. Expression patterns for six of these (CD44, PTEN, DDIT3, ALOX5, VEGFA, and NCF2) were validated in the GSE30529 dataset. Nephroseq data indicated that the mRNA expression levels of CD44, PTEN, ALOX5, and NCF2 were negatively correlated with the glomerular filtration rate (GFR), while VEGFA and DDIT3 mRNA expression levels were positively correlated with GFR. Immune infiltration analysis demonstrated altered immunity in DN patients. Real-time quantitative PCR (qPCR) analysis showed that ALOX5, PTEN, and NCF2 mRNA levels were significantly upregulated in high-glucose-treated human proximal tubular (HK-2) cells, while DDIT3 and VEGFA mRNA levels were significantly downregulated. Immunohistochemistry analysis of human renal biopsies showed positive staining for ALOX5 and NCF2 protein in DN samples but not the controls. These key genes may be involved in the molecular mechanisms underlying ferroptosis in patients with DN, potentially through specific metabolic pathways and immune/inflammatory mechanisms.

Introduction: 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., Methods: 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., Results: 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)., Conclusions: 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).

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)