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A teenage girl presented with fever after aspirin use. Examination revealed no organ-specific symptoms. The serum creatinine level and urine analysis findings were normal. The drug lymphocyte stimulation test was positive for aspirin. Diffusion-weighted magnetic resonance imaging (DW-MRI) revealed hyperintensity in both kidneys although serum creatinine was only mildly elevated. A subsequent kidney biopsy confirmed acute interstitial nephritis (AIN). She later developed uveitis and the final diagnosis was tubulointerstitial nephritis and uveitis (TINU) syndrome, possibly triggered by aspirin, requiring systemic and topical corticosteroid therapies. TINU syndrome should be considered in young patients with fever of unknown origin and a history of nonsteroidal anti-inflammatory drug use. This is the first reported case suggesting the usefulness of DW-MRI, which is safe for children without exposure to ionising radiation, in detecting early-stage AIN before apparent kidney impairment.

A 67-year-old man was referred to the renal team following an episode of acute kidney injury on a background of chronic kidney disease. He had a 9-year history of steroid-sensitive arthritis, epigastric pain and isolated submandibular gland enlargement. He was noted to have a raised eosinophil count, total serum protein and total immunoglobulin G4 (IgG4) level as well as a serum hypocomplementaemia. A renal biopsy showed a tubulointerstitial nephritis with lymphoplasmacytic infiltrates, fibrosis and IgG4-positive plasma cells on immunohistochemistry. A diagnosis of IgG4-related disease was made based on clinical presentation and pathology. Renal function improved with glucocorticoids and the patient was successfully transitioned to azathioprine as a steroid-sparing agent.

Since their introduction into clinical practice a decade ago, immune checkpoint inhibitors (ICIs) have had an overwhelming impact on cancer treatment. Use of these agents in oncology continues to grow; however, the increased use of these agents has been associated with a parallel increase in ICI-associated immune-related adverse events, which can affect virtually any organ, including the kidneys. ICI-associated acute kidney injury (ICI-AKI) occurs in 2-5% of patients treated with ICIs. Its occurrence can have important consequences, including the temporary or permanent discontinuation of ICIs or other concomitant anticancer therapies and the need for prolonged treatment with corticosteroids. Various mechanisms have been proposed to underlie the development of ICI-AKI, including loss of tolerance to self-antigens, reactivation of drug-specific effector T cells, and the production of kidney-specific autoantibodies. ICI-AKI most commonly manifests as acute tubulo-interstitial nephritis on kidney biopsy and generally shows a favourable response to early initiation of corticosteroids, with complete or partial remission achieved in most patients. The evaluation of patients with suspected ICI-AKI requires careful diagnostic work-up and kidney biopsy for patients with moderate-to-severe ICI-AKI to ensure accurate diagnosis and inform appropriate treatment.

Medications are a common cause of AKI, especially for patients admitted to hospital wards and the intensive care unit. Although drug-related kidney injury occurs through different mechanisms, this review will focus on three specific types of tubulointerstitial injury. Direct acute tubular injury develops from several medications, which are toxic to various cellular functions. Their excretory pathways through the proximal tubules contribute further to AKI. Drug-induced AKI may also develop through induction of inflammation within the tubulointerstitium. Medications can elicit a T cell-mediated immune response that promotes the development of acute interstitial nephritis leading to AKI. Although less common, a third pathway to kidney injury results from the insolubility of drugs in the urine leading to their precipitation as crystals within distal tubular lumens, causing a crystalline-related AKI. Intratubular obstruction, direct tubular injury, and localized inflammation lead to AKI. Clinicians should be familiar with the pathogenesis and clinical-pathologic manifestations of these forms of kidney injury. Prevention and treatment of AKI relies on understanding the pathogenesis and judiciously using these agents in settings where AKI risk is high.

One of the common causes of acute kidney injury (AKI) is drug nephrotoxicity. A large group of drugs associated with AKI includes a considerable number of antimicrobials. Clinical manifestations range from mild forms of tubular damage to significant deterioration of renal function requiring renal replacement therapy. Several mechanisms have been described, although the most common are acute interstitial nephritis, acute tubular necrosis, crystalic nephropathy or proximal/distal tubulopathy with electrolyte abnormalities. General risk factors for antimicrobial-induced AKI include pre-existing chronic kidney disease and concomitant use of drugs with nephrotoxic potential. Prevention and early recognition of AKI are the standard approach to mitigate AKI and avoid morbidity.

Drug-induced kidney injury has historically been associated with renal tubule injury related to small molecule pharmaceuticals such as nonsteroidal anti-inflammatory drugs, antineoplastic agents, or antibiotics, but as a greater number of alternative classes of medicines such as biotherapeutics, molecular-targeted antineoplastic drugs, chimeric antigen receptor T-cell therapies, antibody-drug conjugates, oligonucleotide therapies, or other immunomodulatory drugs come to market, the presentation of drug-induced nephrotoxicity is changing. This review article describes the potential rare clinical events in drug-induced kidney injury that might be noted with these new therapies and their potential impact on patients. Potential pathogenic mechanisms related to immunogenicity, immune complex formation, and stimulation of downstream proinflammatory pathways with some of these alternative medicine classes have resulted in the potential for glomerulonephritis, acute interstitial nephritis, renal vasculitis, and other immune-mediated renal disorders in humans. This contrasts with nonclinical toxicity studies, where biologic therapies more often result in vasculitis and glomerulonephritis associated with antidrug antibodies and immunomodulatory pharmacology, and which are not always predictive of clinical effects. While nonclinical antidrug antibody-related renal disease is generally not clinically relevant, other immune-mediated nephrotoxicities associated with immunomodulatory drugs may be predictive of clinical adverse events. Fortunately, these conditions are still rare and account for a small percentage of serious adverse events in kidneys of patients.

Tubulointerstitial nephritis (TIN) is an important cause of acute kidney injury (AKI) and advanced CKD. Only a limited number of studies have reported etiology-based differences in the clinical and/or histopathological properties and kidney outcomes of the biopsy-proven TIN.Patients with biopsy-proven TIN identified from 2005 to 2016 in five hospitals were categorized based on the etiologies and were retrospectively analyzed in relation to the clinicopathological findings and kidney outcomes.Among 4815 biopsy cases screened, 153 Japanese TIN patients were identified, of whom 139 patients with ≥ 6 months of follow-up data (median 58 years old, 45.3% female, median 31.5 months follow-up) were further analyzed. TIN was drug-induced in 32.4%, autoimmune-related in 24.5%, of unknown etiology in 27.3% and other disease-related in 15.8%. Non-steroidal anti-inflammatory drugs and antibiotics were major causative drugs in drug-induced TIN, and IgG4-related disease, Sjögren's syndrome and sarcoidosis were common in autoimmune-related TIN. Among etiology groups, drug-induced TIN showed advanced AKI with elevated serum creatinine (sCr) and increased C-reactive protein levels at the diagnosis. TIN patients with autoimmune diseases showed less-severe AKI, but were more frequently treated with corticosteroids than others. Tubulointerstitial injury expansion in biopsy specimens was comparable among the groups. Complete or partial kidney function recovery at 6 months was more frequent in drug-induced and autoimmune-related TIN than in others. sCr levels at 6 months were similar among the groups.This largest case series study of the biopsy-proven TIN in Japan provides detailed information regarding both etiology-based clinicopathological properties and kidney outcomes.

Acute kidney injury occurs in about 30% of patients hospitalized with coronavirus disease 2019 (COVID-19) and is one of the most common extrapulmonary complications of this disease. The highest risk of acute kidney injury is found in hospitalized patients who require mechanical ventilation. The pathogenesis of acute kidney injury in COVID-19 is multifactorial and seems to not be fully understood. Both direct and indirect mechanisms of kidney injury caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be considered. The histological picture of kidney specimens obtained from patients with acute kidney injury in the course of COVID-19 is dominated by acute tubular necrosis. Some patients also have acute interstitial nephritis, blood clots in the kidney vessels and focal segmental glomerulosclerosis (the variant with collapsing vascular loops). Acute kidney injury in COVID-19 is primarily caused not by direct viral effect, but by indirect pathophysiological mechanisms. The histopathological findings in these patients does not differ from the majority of the other patients with acute kidney injury. The main pathophysiological mechanisms underlying acute kidney injury in COVID-19 are: hemodynamic abnormalities, hypoxia and cytokine storm. The methods of treating the underlying disease, i.e., COVID-19 in patients with acute kidney injury and those without acute kidney injury are similar. However, it should be stressed that in the treatment of COVID-19 accompanied by acute kidney injury, the contraindication to remdesivir is estimated using glomerular filtration rate (eGFR)30 mL/min/1.73 m2. The general principles of management in patients with both, COVID-19 and acute kidney injury do not differ from the principles of management in patients with acute kidney injury due to the other causes.

We have described two clinical cases of severe malaria caused by different pathogens: Pl. falciparum and Pl. malaria, common to which there was a severe course, complicated by acute renal failure and hemolytic anemia. In a detailed analysis of both clinical cases, Patient 1 had acute kidney damage arose after the increase of anemia and thrombocytopenia, in combination with hemoglobinuria. This shows that the leading mechanism of kidney injure in this case is acute tubular necrosis, due to the toxic effects of free hemoglobin and sequestration in the capillaries of the glomerulus. A Patient 2 had a significant increase of anemia after appears of acute kidney damage; there was no hemoglobinuria, however, significant leukocytosis was observed. It seems, that the leading mechanism in this case is immune-mediated kidney injure or due to hypoperfusion of kidney tubules with the development of acute interstitial nephritis or immune complex glomerular injure with the development of glomerulonephritis, or a combination of them. A detailed analysis of the described two clinical cases of severe malaria caused by Pl. falciparum and Pl. malaria, respectively, and complicated by acute renal failure and hemolytic anemia, suggests that the pathogenetic mechanisms and severity of kidney damage depend on the type of malaria.

Drug abuse has become a major problem of the modern world where drug-induced kidney injury can be caused by both prescribed drugs for clinical conditions and illegal (illicit) drugs or drugs of abuse. Heroin, cocaine, nicotine and alcohol are the most commonly abused drugs but with the emergence of various synthetic drugs, numerous novel descriptions of their nephrotoxic effects have been described. This review summarizes the key renal manifestations of recreational drugs as reported in case reports and case. A comprehensive review of published case reports and case series in English language of renal toxicity related to recreational drugs/drugs of abuse was conducted using search engines like PubMed/Medline. Publications which reported renal injury with raised creatinine levels, clinically symptomatic patients, those with oliguria and with renal biopsies are chosen. The medical literature on recreational drugs is full of claims of renal complications including different glomerular diseases, acute kidney injury, rhabdomyolysis, interstitial nephritis, and debilitating irreversible conditions like renal infarction and end stage renal disease, even though the pathogenesis of drug- related renal manifestations are not available for all the newer agents. The outcome of this review paper will help multidisciplinary physicians to understand the renal side effects of recreational drugs, their pathophysiology, and most importantly, the clinical presentations of renal dysfunction in relation each drug. Emphasizing these adverse effects will prevent future unfavorable outcomes.

The presented clinical observation reflects the difficulties of differential diagnosis of progressive kidney damage in a patient with sarcoidosis who has undergone a new coronavirus infection. The differential circle included interstitial nephritis as an exacerbation of the underlying disease, acute drug-induced kidney injury, acute glomerulonephritis. Nephrobiopsy confirmed the diagnosis of acute sarcoid tubulointerstitial nephritis with acute tubular necrosis. Timely administration of corticosteroids led to the control of the sarcoidosis process, restoration of kidney function.В представленном клиническом наблюдении отражены трудности дифференциальной диагностики прогрессирующего поражения почек у больного саркоидозом, перенесшего новую коронавирусную инфекцию. Дифференциальный круг включал интерстициальный нефрит как обострение основного заболевания, острое лекарственное поражение почек, острый гломерулонефрит. Нефробиопсия подтвердила диагноз острого саркоидозного тубулоинтерстициального нефрита с острым канальцевым некрозом. Своевременное назначение кортикостероидов привело к контролю саркоидозного процесса, восстановлению функции почек.

From 2000, Mesoamerican region has reached an important rate of chronic kidney disease of unknown etiology. Under the name of Meroamerican Nephropathy (MeN) several hypotheses (including dehydration, heat stress, environmental or toxic exposure or even infections) have tried to explain the etiology this new disease. MeN affects young men, agricultural workers exposed to high temperatures. MeN courses with unspecific symptoms as low-grade fever and dysuria and progressive kidney disease with impaired renal function and hydroelectrolyte disturbances. The diagnosis requires kidney biopsy showing tubule-interstitial nephritis (usually at chronic stage). Although MeN conditions a high morbi-mortality in endemic regions, there is a lack of specific treatment and only preventive measures have demonstrated some effect of prognosis (avoid heat stress, constant hydration). In this review we aim to summarize the available information of MeN, illustrating the information in a case report. Resumen: Desde el año 2000, la región de Mesoamérica ha presentado una elevada incidencia de casos de enfermedad renal crónica de origen desconocido. Bajo el nombre de nefropatía endémica mesoamericana (NeM) han concurrido numerosas hipótesis incluyendo la deshidratación, el estrés por calor, la exposición a contaminantes ambientales e incluso determinadas infecciones, sin que actualmente exista unanimidad en la etiología de dicha patología. La NeM afecta principalmente a varones jóvenes dedicados a actividades agrícolas con antecedente de exposición a temperaturas especialmente elevadas. Clínicamente cursa con síntomas inespecíficos como febrícula y disuria y analíticamente con deterioro de función renal y alteraciones hidroelectrolíticas. El diagnóstico exige de la realización de una biopsia renal que muestra invariablemente datos de nefritis tubulointersticial principalmente crónica. A pesar de que la NeM condiciona una elevada morbimortalidad en las regiones endémicas, no existe un tratamiento específico por lo que la prevención, basada en disminuir la exposición a elevadas temperaturas y asegurar el correcto estado de hidratación son de gran importancia. En la presente revisión, y basándonos en un caso clínico, actualizamos la evidencia disponible sobre un problema de salud pública con relevantes consecuencias renales.

Polyomavirus associated nephropathy (PyVAN) continues to be a burden in renal transplantation leading to allograft insufficiency or graft failure. A presumptive diagnosis of PyVAN is made based on the presence of BK polyomavirus in patients' plasma; however, kidney biopsy remains the gold standard to establish a definitive diagnosis. The Banff Working Group on PyVAN proposed a novel classification of definitive PyVAN based on polyomavirus replication/load level and the extent of interstitial fibrosis. The aim of our study was to test the newly defined classes of PyVAN using independent cohorts of 124 kidney transplant patients with PyVAN with respect to the initial presentation and outcome, and to compare our analysis to that previously reported. Detailed analysis of our cohort revealed that the proposed classification of PyVAN did not stratify or identify patients at increased risk of allograft failure. Specifically, while class 3 was associated with the worst prognosis, there was no significant difference between the outcomes in classes 1 and 2. We also found that the timing post-transplantation and inflammation in areas of interstitial fibrosis and tubular atrophy might be additional factors contributing to an unfavorable allograft outcome in patients with PyVAN.

The extracellular matrix (ECM) is a complex network of collagens, elastin, and interconnecting glycoproteins and proteoglycans that surround cells and provide structural support. The ECM is a dynamic structure, undergoing constant remodeling, and providing services beyond a simple barrier or scaffold (1). Recent studies have demonstrated that the ECM and the broad complement of interacting proteins ( e.g. the matrisome) play significant roles in inflammation and cell-to-cell interactions (2). Low-grade inflammation, a common feature of many kidney diseases, often contributes to aberrant ECM deposition and fibrosis. Significantly, renal fibrosis is a hallmark of renal dysfunction progression and CKD, leading to end-organ failure. Many of the proteins making up the renal ECM are spatially resolved into the glomerular (glomerular basement membrane, the mesangial matrix, and Bowman’s capsule) and tubulointerstitial (tubular basement membranes, tubular capillaries, and interstitial space) compartments. The most abundant proteins in the ECM are collagens, accounting for almost one third of ECM proteins (3). Type IV collagen is the most well described ECM protein in terms of kidney disease. Type IV collagen has six alpha chains that form three different trimer combinations, and the α3.α4.α5 heterotrimer is the most predominant in the glomerular basement membrane (3). Mutations in COL4A3 , COL4A4 , or COL4A5 genes are associated with Alport Syndrome, thin basement membrane disease, and familial FSGS (4,5). Proteomic analysis has identified collagens I, III, VI, VII, XII, XV, and XVIII within the glomerular ECM (6,7). Collagens I, II, III, V, VI, VII, and XV are normally expressed in the tubulointerstitium and increased expression have been associated with fibrosis (3). A recent proteomic analysis of kidneys across different age groups demonstrated consistent increases in collagen VI with aging kidneys (8). Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE), …