Chronic Interstitial Nephritis Research Articles

A NEPHROPROTECTIVE EFFECT OF CARISSA SPINARUM AGAINST GENTAMICIN INDUCED OXIDATIVE NEPHROTOXICITY

One of the most prevalent issues with the kidneys is nephrotoxicity, which happens when the body is exposed to a toxin or medicine. With the growing availability of powerful therapeutic medications such as aminoglycoside antibiotics, chemotherapeutic agents, and nonsteroidal anti-inflammatory drugs (NSAIDs), a variety of pharmaceuticals can have a negative impact on the kidney, leading to acute renal failure, chronic interstitial nephritis, and nephritic syndrome. Ethiopian native Carissa spinarum (Apocynaceae) is traditionally used to treat skin conditions, rheumatism, diarrhoea, chicken pox, and stomachaches. The herbal plant Carissa spinarum possesses antioxidant qualities. The term "nephrotoxicity" describes the detrimental effects that different drugs can have on the kidneys, which can result in damage and dysfunction. This illness offers a serious risk to kidney health and can be brought on by exposure to specific medicines, chemicals, or poisons. Understanding the methods by which these substances affect the structure and function of the kidneys—such as oxidative stress, inflammation, and interference with essential cellular processes—is necessary to comprehend the abstract idea of nephrotoxicity. Nephrotoxicity management also involves establishing prevention and management strategies, identifying, and tracking possible nephrotoxic substances, and managing and preventing nephrotoxicity. All things considered, an abstract comprehension of nephrotoxicity entails investigating the complex pathways and circumstances that lead to renal injury and formulating strategies to lessen or offset these detrimental effects on kidney function.

Systematic Review of Kidney Injury Biomarkers for the Evaluation of CKD of Uncertain Etiology

IntroductionChronic kidney disease of uncertain etiology (CKDu) is an incompletely defined phenotype of CKD affecting young individuals mostly in agricultural communities in Central America and South Asia. CKDu is a diagnosis of exclusion made in individuals from endemic regions. MethodsWe conducted a systematic review of the primary literature on urinary and plasma kidney injury biomarkers measured in the setting of CKDu (through February 2023). Literature was identified via a Web of Science search and hand search of the references of previously identified literature. Search terms included “CKDu,” “Mesoamerican Nephropathy,” “CKD of unknown etiology,” “Chronic Interstitial Nephritis in Agricultural Communities,” “biomarker,” “urin*,” and/or “plasma.” ResultsA total of 25 papers were included. The two most frequently measured biomarkers were urinary kidney injury molecule-1 and urinary neutrophil gelatinase-associated lipocalin. There was substantial variability in study design, laboratory assay methods, and statistical methodology which prohibited meta-analysis. ConclusionBiomarkers that identify tubulointerstitial disease early and accurately may substantially accelerate progress in the study of CKDu and facilitate public health approaches that eventually lead to its prevention and elimination. To date, the literature is limited by relatively small sample sizes and methodological limitations which should be addressed in future studies.

Models of gouty nephropathy: exploring disease mechanisms and identifying potential therapeutic targets.

Gouty nephropathy (GN) is a metabolic disease with persistently elevated blood uric acid levels. The main manifestations of GN are crystalline kidney stones, chronic interstitial nephritis, and renal fibrosis. Understanding the mechanism of the occurrence and development of GN is crucial to the development of new drugs for prevention and treatment of GN. Currently, most studies exploring the pathogenesis of GN are primarily based on animal and cell models. Numerous studies have shown that inflammation, oxidative stress, and programmed cell death mediated by uric acid and sodium urate are involved in the pathogenesis of GN. In this article, we first review the mechanisms underlying the abnormal intrinsic immune activation and programmed cell death in GN and then describe the characteristics and methods used to develop animal and cell models of GN caused by elevated uric acid and deposited sodium urate crystals. Finally, we propose potential animal models for GN caused by abnormally high uric acid levels, thereby provide a reference for further investigating the methods and mechanisms of GN and developing better prevention and treatment strategies.

Nephrological Detrimental Impacts Resulting From Novel Immunotherapy Drugs Used in the Treatment of Cancer: A Systematic Review.

The most recent advancements in cancer therapycenter on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs) are antibodies that target cytotoxic thymus (T) lymphocyte antigen-4 (CTLA-4) and its receptor. They function by stimulating T-cell activity against malignancies. Immune-related adverse events (irAEs) are a distinct class of inflammatory side effects that are specific to a given organ. Antineoplastic medications can impact any part of the kidney, leading to the development of proteinuria, hypertension, electrolyte abnormalities, glomerulonephritis, and both acute and chronic interstitial nephritis. We reviewed the scientific literature regarding kidney problems that can arise from chemotherapy and immunotherapy for neoplasms, such as various cancers, melanoma, non-small cell lung cancer, and colorectal cancer. We discussed the pathophysiology, associated risk factors, management, and safety measures for patients experiencing acute renal injury after a new immunotherapy medication treatment. Antineoplastic drugs have the potential to damage the renal tubules, glomeruli, parenchyma, and blood vessels, among other kidney tissues. This can result in a broad spectrum of complications, spanning from a rise in serum creatinine levels without symptoms to the development of acute kidney injury (AKI). The research examined a range of risk factors associated with acute kidney injury (AKI). These factors encompassed age, gender, preexisting medical conditions (such as diabetes, hypertension, and chronic kidney disease), and the medications that patients were taking at the beginning of the study, which included non-steroidal anti-inflammatory drugs,renin-angiotensin system inhibitors, allopurinol, diuretics, corticosteroids, and proton pump inhibitors. The data suggests that patients who were receiving baseline treatment with proton pump inhibitors (PPIs) or corticosteroids had a higher risk of mortality. This study serves as an illustration of the effective management of acute kidney injury and proteinuria linked to novel immunotherapy drugs like pembrolizumab. The approach involved the use of corticosteroids tailored to the patient's condition. Furthermore, it references the recommendations outlined in the Common Terminology Criteria for Adverse Events (CTCAE). Prompt recognition and effective management of these side effects are essential to optimizingoutcomes for patients undergoing immunotherapy. Our results were refined and focused by utilizing Medical Subject Headings (MeSH) keywords in our search strategy. The MeSH keywords used were "renal side effects" OR "immunotherapy" OR "cancer treatment." The studies reviewed encompassed a total of 48,529 participants among the 21 studies examined.

An unintended connection – Radial arteriovenous fistula after coronary angiogram

Abstract The following case is of a 44-year-old female undergoing maintenance hemodialysis (MHD) due to chronic interstitial nephritis, utilizing a left brachiocephalic (BC) arteriovenous fistula (AVF). Following presentation with retrosternal anginal pain, diagnosed as high lateral wall myocardial infarction, coronary angiogram revealed normal coronaries. Subsequently, dilated veins along the right forearm were noticed, attributed to a patent right radiocephalic AVF. Despite being asymptomatic, the patient underwent a Doppler ultrasound confirming a blood flow of 400 ml/min through the AVF. No further intervention was planned as the patient continued MHD through the left BC AVF.

Efficacy of Reverse Osmosis in Reducing Chronic Kidney Disease of Unknown Etiology in Sri Lanka: A Narrative Review 

There has been an epidemic of Chronic Kidney Disease of Unknown Etiology (CKDu) affecting the agricultural communities in Sri Lanka, spanning three decades. The main pathological finding has been chronic interstitial nephritis. This narrative review focuses on the efficacy of Reverse Osmosis (RO) technology in purifying water and its impact in reducing CKDu. PubMed, Cochrane and Google Scholar were used to search for peer-reviewed articles from 2000 to 2023. The themes that emerged from the literature review were validated through the opinions of key informants and subject matter experts.There were anecdotal, as well as some research evidence to indicate that RO-treated water is efficacious in preventing and slowing down the progression of CKDu. This relationship needs further investigation with well-designed prospective studies. The literature review also revealed many social, technical and environmental issues related to the use of RO machines. Despite the potential benefits of RO machines, these issues must be resolved in order to prevent serious problems in the future.In conclusion, this review underscores the need for further research, interventions and regulatory measures related to the use of RO machines to reshape the CKDu trajectory in Sri Lanka.

Chronic Interstitial Nephritis in Agricultural Communities

Chronic Interstitial Nephritis in Agricultural Communities

Dilemma of chronic kidney disease of unknown origin

Over the past two decades, cumulative increases in the prevalence of chronic kidney disease (CKD) have been observed in selected geographic areas in several countries. The etiology of this CKD cannot be attributed to known or traditional causes or risk factors, and the term chronic kidney disease of unknown etiology (CKDu) has been used to describe this entity. These regional endemic nephropathies are commonly known as CKD of unidentified cause (CKDu) or CKD of nontraditional etiology (CKDnt) and, more recently, Chronic interstitial nephritis of agricultural communities (CINAC). Unlike the traditional causes of CKD (i.e., Hypertension, Diabetes, chronic glomerulonephritis, etc), CKDu has been associated with agricultural and arid regions. Also, the socioeconomic state of those regions is key. This review addresses the present status of the knowledge for different aspects of this regional health problem as well as summarizes available evidence on the risk factors, epidemiology, clinical features, diagnosis, treatment, and prevention of CKDu. It will also highlight the reasons why Africa should be concerned about this condition. Using the keywords “Africa, CKD of unknown origin,” a literature search was conducted on PubMed, Scopus, and Google Scholar, focusing on the research published between 2000 and 2022. Results from the literature show that predisposition to heat stress and dehydration, subclinical rhabdomyolysis, toxins from alcoholic beverages, agrochemicals, and heavy metals all result in acute kidney injury, and repeated exposures to these factors can then cause CKDu. Earlier studies in Sri Lanka nephropathy by Nanayakkara and his team in 2014 identified that a genetic variant of SLC13A3 (sodium-dependent dicarboxylate transporter member 3) is associated with CKDu. Later research conducted in 2015 discovered KCNA10 (a voltage-gated potassium channel) also as a gene implicated in CKDu; these genetic variances were discovered to be common among the populace suffering from kidney diseases, hence suggesting that, people with these genes have a high risk of developing kidney disease. Predisposition to heat stress and dehydration, subclinical rhabdomyolysis, and toxins from alcoholic beverages, agrochemicals, and heavy metals all results in acute kidney injury, and repeated exposures to these factors can then cause CKDu. Also, certain genes have been found to be associated with CKDu.

Chronic dehydration induces injury pathways in rats, but does not mimic histopathology of chronic interstitial nephritis in agricultural communities

CINAC-patients present renal proximal tubular cell lysosomal lesions which are also observed in patients experiencing calcineurin inhibitor (CNI) nephrotoxicity, suggesting that CINAC is a toxin-induced nephropathy. An alternative hypothesis advocates chronic dehydration as a major etiological factor for CINAC. Here, we evaluated histological and molecular changes in dehydrated versus toxin exposed rats. Wistar rats were divided in 3 groups. Group 1 (n = 6) had free access to drinking water (control group). Group 2 (n = 8) was water deprived for 10 h per 24 h, 5 days/week and placed in an incubator (37 °C) for 30 min/h during water deprivation. Group 3 (n = 8) underwent daily oral gavage with cyclosporine (40 mg/kg body weight). After 28 days, renal function, histopathology and proteomic signatures were analysed. Cyclosporine-treated rats developed focal regions of atrophic proximal tubules with associated tubulo-interstitial fibrosis. PASM staining revealed enlarged argyrophilic granules in affected proximal tubules, identified as lysosomes by immunofluorescent staining. Electron microscopy confirmed the enlarged and dysmorphic phenotype of the lysosomes. Overall, these kidney lesions resemble those that have been previously documented in farmers with CINAC. Dehydration resulted in none of the above histopathological features. Proteomic analysis revealed that dehydration and cyclosporine both induce injury pathways, yet of a clear distinct nature with a signature of toxicity only for the cyclosporine group. In conclusion, both cyclosporine and dehydration are injurious to the kidney. However, dehydration alone does not result in kidney histopathology as observed in CINAC patients, whereas cyclosporine administration does. The histopathological analogy between CINAC and calcineurin inhibitor nephrotoxicity in rats and humans supports the involvement of an as-yet-unidentified environmental toxin in CINAC etiology.

Chronic Interstitial Nephritis in Agricultural Communities: Observational and Mechanistic Evidence Supporting the Role of Nephrotoxic Agrochemicals.

Chronic interstitial nephritis in agricultural communities (CINAC) is an epidemic of kidney disease affecting specific tropical and subtropical regions worldwide and is characterized by progressive CKD in the absence of traditional risk factors, such as hypertension and diabetes. CINAC prevalence is higher among young, male agricultural workers, but it also affects women, children, and nonagricultural workers in affected areas. Biopsies from patients with CINAC across regions commonly demonstrate tubular injury with lysosomal aggregates, tubulointerstitial inflammation, and fibrosis and variable glomerular changes. Each endemic area holds environmental risk factors and patient/genetic milieus, resulting in uncertainty about the cause(s) of the disease. Currently, there is no specific treatment available for CINAC. We highlight survey findings of Houston-based migrant workers with CINAC and draw similarities between kidney injury phenotype of patients with CINAC and mice treated chronically with paraquat, an herbicide used worldwide. We propose potential pathways and mechanisms for kidney injury in patients with CINAC, which may offer clues for potential therapies.

Live Related Kidney Transplantation: Experience of 360 Patients in a Tertiary Care Hospital of Bangladesh

Background: Live related kidney transplantation is the most preferred form of renal replacement therapy worldwide including Bangladesh. However, it is challenging and also rewarding both for patients and treating physicians. BSMMU hospital has given maximum effort for its greater success. The aim of this study was to share our ten years’ experience regarding some aspects of live related renal transplantation. Methods: This retrospective study was conducted in nephrology department of BSMMU hospital from January 2002 to December 2015. Data were collected from hospital records and some previously conducted study on these transplant recipients. Results: A total of 360 live related kidney transplant recipients were evaluated during this period. Recipients Male: Female ratio was 1.57:1. Mean age of recipients were 39.58 ± 10.46 years. The causes of ESRD were chronic glomerulonephritis 220(61.60 %), diabetic nephropathy 58(16.24%), hypertensive nephrosclerosis 22 (6.16 %), chronic interstitial nephritis 11 (3.08 %), SLE 10(2.8%), ADPKD 6(1.68 %), unknown 19(5.32 %). Most of the donors were mother (21.84% %) followed by spouse mostly wife (20.44%) and sister (18.76 %). Almost all recipients were on MHD 352(97.78%), 2 were on CAPD and 06 were pre-emptive transplantation. Triple immunosuppressive protocol Cyclosporine or Tacrolimus, MPA or Azathioprine and Prednisolone were used in each patient. Recipients with poor HLA matching received Baciliximab in standard dose. CMV prophylaxis was given in selected patients and each patient received pneumocystis jirovecii prophylaxis. Common complications during post-operative period were ATN 41(11.48%), DGF 23(6.44%), Acute rejection 50(14%) and infection mainly urinary tract infection 46(12.88%) and RTI 14(3.92) followed by wound infection and other surgical complication. Presence of BK virus infection was studied in 29 transplant recipient and it was found to be positive in 6(20.7%) cases. Protocol biopsy was done in 37 transplant recipient in the 2008-2009 on day 14, and day 90 to see subclinical rejection and early graft dysfunction. On day 14th biopsy report showed 21(56.7%) normal histology, 5(13.5%) had subclinical rejection, 5(13.5%) had clinical rejection, 4(10.8 %) developed ATN, 2(5.2 % ) cyclosporine toxicity, and report at 3 month showed normal histology 18(48.60%), subclinical rejection 7(18.90%), clinical rejection 5(10.80%). Leading cause of chronic allograft dysfunction was chronic allograft nephropathy (CAN) 60(19.80%) followed by chronic cyclosporine toxicity 37(12.21%) and de-novo or recurrent glomerulonephritis. Mean post-transplant hospital stay was 18.46 ± 5.56 days. Mean duration of normalization of serum creatinine after surgery was 7.38 ± 3.88 days. At discharge 74.40% patients had normal renal function with mean serum creatinine 1.10 ± 0.26 mg/dl and 21.34% patients showed gradual improvement of renal function with mean serum creatinine 2.12 ± 0.97 mg/dl. In our study 1 year and 5 years’ graft survival was 93.88% and 75.16% respectively and 1 year and 5 years’ patient’s survival was 346(96.08%) and 290(81.2%). Conclusion: Our report shows that short and long term graft and patient survival is encouraging and comparable to other centers of both developing and some developed countries with limited resources and facilities.

#5158 AUTOSOMAL DOMINANT TUBULAR KIDNEY DISEASE: FROM PHENOTYPE TO GENOTYPE

Abstract Background and Aims Autosomal dominant tubulointerstitial kidney disease (ADTKD) represent a recently described group of kidney diseases, characterized by chronic interstitial nephritis (CIN), in most cases hereditary, with an autosomal dominant inheritance pattern, subclassified according to its genetic cause, when identified. Mutations in UMOD, MUC1, REN and HNF1B genes have been implicated in their pathogenesis. Recent molecular diagnostic technologies, such as Next-Generation Sequencing (NGS), and particularly the use of restriction and Snapshot method for the detection of a cytosine insertion on the coding variable-number tandem repeat (VNTR) sequence in the MUC1 gene encoding mucin 1, have allowed the nephrologists to diagnose renal diseases of previously unknown cause, with a real prevalence probably underestimated. We present the cohort of patients identified with ADTKD in the Nephrogenetics’ clinic from the Nephrology department of our hospital from 2015 to 2022. Method Patients with chronic kidney disease (CKD) of unknown etiology and renal phenotype suggesting CIN (bland urine analysis, hyperuricemia and/or anemia unrelated to the degree of CKD, hypo/hypercalcemia, acidemia, urinary concentration defects, absent hypertension, renal cysts), especially with a family history of similar CKD, were referred for the Nephrogenetics’ clinic and ADTKD was investigated. In these cases, we performed a genetic study of ADTKD by the following steps: 1) UMOD, REN, HNF1B mutations studied through NGS; 2) if negative, search for the insertion of a single cytosine of the repeat unit comprising the extremely long (∼1.5-5 kb), GC-rich (>80%) coding variable-number tandem repeat (VNTR) sequence in the MUC1 gene encoding mucin 1 (see Kirby et al Nat Genet. 2013). It is used a restriction and Snapshot method. 3) if negative, search for HNF1B Large deletion, detected by MLPA (kit P241-D2, MRC-Holland). Pre-genetic counselling was performed by the nephrologist, and post-genetic counselling was performed by the nephrologist and geneticist, namely to proceed with family screening of potentially affected family members when a pathogenic mutation was identified or when segregation studies were necessary. Results 31 families were studied and a confirmed genetic diagnosis was obtained in 11 (35%), allowing the identification of 30 patients with ADTKD; the mutations identified were in MUC1 in 4 families (13 patients), UMOD in 4 families (11 patients), HNF1B (2 families, 5 patients) and REN: 1 patient with a phenotype compatible with ADTKD but with a genotype compatible with renal tubular dysgenesis (two mutations in REN gene from each of the parents). One patient with HNF1B deletion also presented with a heterozygous variant of unknown significance in PKD1 gene, and a pathogenic variant of SLC12A3, heterozygous. Three families are still under study: 2 families are being studied with segregation studies to evaluate the pathogenicity of mutations in UMOD (1 family) and HNF1B (1 family), and 1 family with a phenotype of ADTKD (3 young patients with positive family history) with negative results for mutations in ADTKD genes is in study, with a negative result in WES. The study will be pursued in a specialized laboratory to better study MUC1, but at this moment we classify this family as ADTKD-NOS. If positive results are obtained for these 3 families, the percentage of families identified using this protocol will increase to 43,3% of the families studied through this model. Conclusion In our cohort, a genetic diagnosis was established in 35% of the families studied. MUC1 and UMOD are the most prevalent genes implicated in ADTKD at our center, similarly to what has been reported in other cohorts of ADTKD. Given the rarity of these diseases and the fact that they require specific molecular techniques for accurate diagnosis, we believe that Nephrogenetics’ clinics with dedicated nephrologists and geneticists in close cooperation are critical for an accurate diagnosis.

#3243 CANCER PATIENTS WITH END-STAGE KIDNEY DISEASE ON CHRONIC HEMODIALYSIS: CHANGING THE PARADIGM

Abstract Background and Aims In the last decade, new therapeutic regimens have dramatically improved the prognosis of cancer patients and changed the paradigm of a previously highly lethal disease, increasing the number of cancer patients with chronic kidney disease (CKD) who progress to end-stage kidney disease (ESKD). However decision-making regarding dialysis initiation in patients with cancer and ESKD remains however controversial. The aim of our study was to characterize the clinical course and evaluate survival outcomes of cancer patients on chronic hemodialysis (HD). Method We conducted a retrospective study of chronic HD patients in a single oncology hospital unit between January 1991 and November 2022. Outpatients on HD for more than one month, who underwent dialysis after the diagnosis of cancer were included. Univariate and multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were estimated using the Cox proportional hazards risk model. Results Two hundred and twelve patients were recruited. Mean age at HD initiation was 65.7±14.7 years. The most prevalent ESKD etiologies were cast nephropathy, chronic interstitial nephritis, and surgical removal of the kidney. The most common tumors were genitourinary, multiple myeloma (MM) and gastrointestinal corresponding to 80.6% of all cancers. There were 143 deaths over a median follow-up period of 23 months (IQR: 7.25 – 54). The overall survival rates were 76.5% at 1 year, 59.6% at 3 years and 39.2% at 5 years. The median survival time was 44 months (95% CI: 30.58 – 51.42). An increased mortality risk was observed in patients with MM (HR: 3.38; 95% CI: 1.01-11.39; p = 0.045) and in those who started HD from 2001 to 2011 (HR: 1.60; 95% CI: 1.06-2.42; p = 0.001). The presence of metastasis or multiple tumors was not associated with all-cause mortality. Conclusion Our results highlight the importance of considering cancer patients for renal support therapies, including those with multiple tumors and metastatic disease. In fact, with the new treatments available, many patients have chronic oncological disease non-fatal in the short term. To the best of our knowledge, this is the largest study of cancer patients on chronic HD.

Chronic Tubulointerstitial Nephropathy of Agricultural Communities

Chronic interstitial nephritis in agricultural communities is an emerging public health concern affecting numerous agricultural communities in tropical countries, including regions in India, with a significant impact on the health and well-being of affected individuals. The affected individuals suffer from various psychosocial, nutritional, and metabolic challenges due to organ failure, which affects their quality of life. The etiology remains poorly understood, and various risk factors, which include various environmental and occupational hazards, have been implicated in its development. The recent discovery of lysosomal proximal tubulopathy has reignited interest in its pathogenesis. Along with the representative feature of chronic interstitial nephritis, changes suggestive of tubular injury have also been reported. It is suggested to use the term “chronic tubulointerstitial nephropathy of agricultural community” instead of chronic interstitial nephritis of the agricultural communities. Chronic tubulointerstitial nephropathy in agricultural communities is a slowly progressive disease that initially does not cause any symptoms in patients and most patients have a delayed onset of symptoms. Several diagnostic criteria have been introduced over the past years and one introduced by the Ministry of Health of Sri Lanka is widely used. The management of this chronic illness is no different from other causes of chronic interstitial nephritis and our focus should be on implementing various preventive strategies to reduce its incidence in agricultural communities and protect the health and well-being of agricultural workers. By disseminating knowledge about chronic tubulointerstitial nephropathy in agricultural communities, we can contribute to the development of evidence-based interventions to reduce the burden of the disease on affected communities. Moreover, we would like to sensitize physicians to this entity to increase awareness and identify potential endemic areas in various agricultural communities.

Afectación renal por fármacos, medios diagnósticos y tóxicos

Some drugs, diagnostic media and toxic substances can cause structural kidney damage, with a negative effect on their function. This is fundamentally because the kidneys are highly vascularized organs and the main means of eliminating many metabolites. Furthermore, the urinary concentration process means that these substances may accumulate in the tubules and interstices, leading to lesions at this level. In general, non-specific harm is caused in the tubulointerstitial parenchyma, with three characteristic lesion patterns: acute interstitial nephritis, chronic interstitial nephritis and acute tubular necrosis. Vascular or glomerular damage occurs less often. To prevent this pathology it is necessary to know which components can be nephrotoxic and how we should use them in patients who are at risk. Withdrawal of the toxic agent is the key to resolving the symptoms.

Enfermedades renales tubulointersticiales. Nefritis intersticial crónica

Interstitial kidney disease covers a group of disorders which cause interstitial inflammation associated with tubular damage. Traditionally, interstitial nephritis has been classified morphologically and clinically as either acute or chronic. Acute interstitial nephritis (AIN) usually induces rapid deterioration of kidney function, with a marked inflammatory interstitial response that is characterized by the infiltration of mononuclear cells with or without eosinophils, interstitial oedema and tubular involvement. On the other hand, chronic interstitial nephritis (CIN) follows a more indolent course, and it is characterized by interstitial fibrosis, tubular atrophy and, almost always, interstitial infiltrate of mononuclear cells. The tubulointerstitial lesion is clinically important because it is a predictor of present and future kidney function.

Karyomegalic interstitial nephritis as a rare cause of kidney graft dysfunction: case report and review of literature

Karyomegalic interstitial nephritis (KIN) is a rare cause of chronic interstitial nephritis characterized by enlarged renal tubular epithelial nuclei. The first case of KIN reported in a kidney graft was in 2019. Here, we report the first case of KIN in 2 brothers receiving kidneys from 2 different unrelated living donors. A male kidney transplant recipient with focal segmental glomerulosclerosis as the original kidney disease presented with graft impairment and proteinuria, and graft biopsy revealed KIN. This patient had a brother who was also a kidney transplant recipient and had one episode of graft impairment and was diagnosed with KIN as well.

24 A Case of Chronic Interstitial Nephritis From an Infiltrative Renal B-cell Lymphoma

24 A Case of Chronic Interstitial Nephritis From an Infiltrative Renal B-cell Lymphoma

Melatonin ameliorates glyphosate- and hard water-induced renal tubular epithelial cell senescence via PINK1-Parkin-dependent mitophagy

The combination of glyphosate (Gly) and hard water (Hwt) is a suspected risk factor for chronic interstitial nephritis in agricultural communities (CINAC). Accumulated mitochondrial damage and proximal tubular epithelial (PTE) cell senescence have been implicated in CINAC pathogenesis. Melatonin (Mel) has potential mitochondrial function and renoprotective properties, but its role and mechanism in CINAC are unknown. Here, we detected PTE cell senescence and PTEN-induced putative protein kinase 1 (PINK1)-parkin RBR E3 ubiquitin protein ligase (Parkin)-dependent mitophagy in mice orally administered with different doses of Gly combined with Hwt (Gly: 100 mg/kg·bw and 0.7 mg/L; Hwt: 2,500 mg/L CaCO3 and 250 mg/L Ca2+) for different durations (12 and 36 w) using histological examination, transmission electron microscopy (TEM), immunofluorescence (IF) analysis, and immunohistochemistry (IHC), immunoblotting, ELISA and biochemical assays with kits. The same assays were performed after combination treatment with Mdivi-1 (an inhibitor of mitophagy, i.p. 10 mg/kg·bw, twice a week for 12 w) or Mel (i.p. 10 mg/kg·bw, once a day for 12 w) under high-level exposure. Gly combined with Hwt (Gly-Hwt) significantly increased P16-P21-dependent PTE cell senescence, mitochondrial fission and oxidative stress, and activated PINK1-Parkin-mediated mitophagy, accompanied by defective autophagic flux at high doses but unaltered autophagic flux at low doses. Improved senescence occurred after Mdivi-1 administration, suggesting that mitophagy is involved in cellular senescence. Mel significantly decreased senescence induced by Gly-Hwt. Furthermore, PINK1-Parkin-dependent mitophagy and autophagic flux were markedly enhanced, and mitochondrial function was improved, as evidenced by reductions in mitochondrial fission and subsequent oxidative damage. Thus, Gly and Hwt synergistically promote PTE cell senescence through PINK1-Parkin-mediated mitophagy, and Mel exerts renoprotective effects by modulating mitophagy, suggesting therapeutic applications in ageing-related CINAC.

Kidney Disease in Ankylosing Spondylitis: a case series and review of the literature.

Kidney disease is a rare manifestation of ankylosing spondylitis (AS) and its pathological alterations remain poorly described. The aim of this study was to investigate the clinical presentation and pathological alterations on kidney biopsy of AS patients and review and discuss the current literature on the issue. We retrospectively studied the clinical presentation and kidney pathological alterations of 15 Caucasian AS patients submitted to kidney biopsy between October 1985 and March 2021. Patients were predominantly male (66.7%) with median age at the time of kideney biopsy of 47 years [IQR 34 - 62]. Median serum creatinine at presentation was 1.3 mg/dL [IQR 0.9 - 3] and most patients also had either proteinuria (85.7%) and/or hematuria (42.8%). The most common indication for kidney biopsy was nephrotic syndrome (33.3%), followed by acute or rapidly progressive kidney injury (20%) and chronic kidney disease of unknown etiology (20%). Chronic interstitial nephritis (CIN) (n=3) and AA amyloidosis (n=3) were the most common diagnosis. Others included IgA nephropathy (IgAN) (n=2), focal segmental glomerulosclerosis (n=2), membranous nephropathy (n=1), and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN)(n=1). We present one of the largest series of biopsy-proven kidney disease in Caucasian AS patients. We found a lower prevalence of IgAN than previously reported in Asian cohorts. We found a higher prevalence of CIN and a lower prevalence of AA amyloidosis than that described in previous series of Caucasian patients. We also present the first case of AS-associated IC-MPGN.