Tubule-interstitial Nephritis Research Articles

Acute Kidney Disease following Acute Kidney Injury in Children-A Retrospective Observational Cohort Study on Risk Factors and Outcomes.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding AKD in children are scarce. The purpose of our study was to explore the risk factors for developing AKD based on exposures and susceptibilities in children with AKI doubled by the biological parameters from the first day of identified AKI. In addition, we followed the trajectory of AKD following an acute kidney injury (AKI) episode in children during hospital admission and after discharge with special considerations towards mortality and progression to new-onset CKD. Methods: We retrospectively evaluated 736 children, ages between 2 and 18 years old, with identified AKI during hospital admission in a tertiary care hospital from west Romania over a 9-year period. Results: AKD incidence following an AKI episode was 17%. Patients who developed AKD were older, with higher baseline serum creatinine, urea, C reactive protein and lower proteins, haemoglobin and sodium levels. In the adjusted model, no biological parameters influenced AKD development. Regarding certain exposures and personal susceptibilities in children with AKI, only anaemia independently increased the risk of AKD development by 2.47 times. However, out of the AKI causes, only the intrinsic causes of AKI independently increased the risk of progressing to AKD (glomerulonephritis by 4.94 and acute tubule-interstitial nephritis by 2.76 times). AKD increased the overall mortality by 2.6 times. The factors that independently increased the risk of CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: Only anaemia, glomerulonephritis and acute tubule-interstitial nephritis increased the risk of AKD development in children with AKI. AKD was an independent risk factor for mortality and new-onset CKD in children.

#2668 New treatments, new challenges: nephrotoxicity associated to naxitamab in patients with high-risk neuroblastoma

Abstract Background and Aims Neuroblastoma is the most common extracranial solid tumor in children, harboring a poor survival for those with high-risk (HR) tumors. Naxitamab (hu3F8) is a humanized monoclonal anti-disialoganglioside (GD2) antibody approved for the treatment of patients older than 1-year with refractory/relapsed HR-neuroblastoma limited to bone and/or bone marrow. First naxitamab (DanyelzaR) infusion was in 2017 in our institution and since then a large experience has been acquired with its use through several clinical trials as well as an expanded named patient access program. The objective is to describe the renal toxicity profile associated to naxitamab in patients with HR-neuroblastoma. Method Retrospective descriptive study including 244 patients treated with naxitamab (either on monotherapy or associated to chemotherapy) from June 2017 to December 2022 in whom renal involvement and/or hypertension (HT) was evaluated. Results Mean age of the cohort was 8 years (41% female -101- and 59% male -143-), presenting nephrotoxicity of some type up to 26.6% (n = 65): AHT (11.9%), acute renal damage (ARD 10.2%) and proteinuria (5.3%), developing all during the first 3 cycles. All of them were classified as mild adverse events (1-2) according to the Common Terminology Criteria for Adverse Events (CTCAE) scale, except for one patient with ARD grade 3 and two patients with HT grade 3. In the case of HT only in 6 patients an Ambulatory Blood Pressure Monitoring (ABPM) was performed, observing: 2 nocturnal-HT, 2 diurnal-HT without specific-pattern and 2 disautonomic-patterns. Among the ARD, all cases were tubular except for two patients who presented acute tubule-interstitial nephritis (AIN) (one with clinical-analytical pattern and another confirmed by biopsy). Eight of them (32%) had potential confounding factors (previous chemotherapy, ibuprofen or radiotherapy). Among patients with proteinuria (none in the nephrotic range): 38% tubular, 38% glomerular and 23% mixed. Two patients presented ARD + HT and 3 a combination of HT + ARD + proteinuria. All patients received prior chemotherapy and 2 developing chronic renal damage (CKD stage 2 and 3). Conclusion Short-and long-term follow-up, the systematic performance of ABPM, and the use of early markers of renal damage, could lead to a more efficient management of complications derived from this new treatment.

A case of IgG4-related interstitial nephritis with ureteral obstruction: case report and literature review

BackgroundIgG4-related disease (IgG4-RD) is a newly discovered systemic disease that can affect any organ or tissue in the body. IgG4-related kidney disease (IgG4-RKD) is relatively rare but essential to IgG4-RD. However, there are few reports of IgG4-RD mimicking malignant ureteral tumors leading to hydronephrosis. We report here a rare case of IgG4-RD involving the ureter.Case presentationAn 87-year-old man presented to our nephrology department with anorexia, nausea, and acute kidney injury in November 2020. Urinary computed tomography (CT) examination revealed a right lower ureter mass with right renal and ureter hydronephrosis. The serum level of IgG4 was 1890 mg/dL, and the concurrently renal biopsy revealed extensive infiltration of IgG4-positive plasma cells in renal interstitium, which was diagnosed as IgG4-associated tubule-interstitial nephritis(IgG4-TIN). The renal function improved significantly after double-J tube implantation of the right ureter and moderate-dose hormone therapy. The serum IgG4 decreased to the normal range, and the right lower ureter mass almost disappeared after one year of low-dose hormone maintenance therapy.ConclusionIgG4-RD can present as a mass in the renal pelvis and (or) ureter, leading to hydronephrosis. Therefore, early recognition of this disease is significant. Most patients respond well to hormonal therapy to avoid surgical treatment due to misdiagnosis as malignant tumors, causing secondary harm to patients.

Patterns of renal toxicity from the combination of pemetrexed and pembrolizumab for advanced nonsquamous non-small-cell lung cancer (NSCLC): A single-center experience

ObjectivesThe combination of immune-checkpoint inhibitors (ICI) and platinum-pemetrexed chemotherapy (CT) in first-line setting improved survival outcomes of advanced non-small cell lung cancer (NSCLC) patients. Among the various adverse events, renal toxicity can be a relevant safety issue. Materials and methodsWe conducted a single-center, observational retrospective study including consecutive patients treated with upfront CT-ICI for advanced nonsquamous NSCLC to investigate incidence and clinical characteristics of acute kidney injury (AKI) using ‘Acute Kidney Injury Working Group of Kidney Disease: Improving Global Outcomes’ (KDIGO) definition. ResultsA total of 89 patients received a first-line CT/ICI. The median age was 69 years. 60.7 % were male, and 87.6 % had an ECOG PS of 0–1. 92.1 % had a baseline glomerular filtration rate of at least 60 ml/min. According to KDIGO criteria, 25 (28 %) patients developed AKI. Considering risk factors for AKI onset, patients receiving >10 cycles of CT/ICI were more likely to experience AKI (p < 0.001). No other associations were found with other variables, including concomitant medications. Any component of the treatment was discontinued (pemetrexed pembrolizumab or both) in 10 (40 %) patients, and 9 patients (36 %) were addressed to nephrological consultation. These patients had higher mean creatinine variation from baseline (1 vs 0.6 mg/dl, p = 0.025) and creatine level (1.8 vs 1.4 mg/dl, p = 0.015), but lower eGFR (35.7 vs 54.2 ml/min, p = 0.011) in comparison to patients not addressed. No patients had microscopic hematuria or pyuria, but mild proteinuria (<0.8 g/24 h) was found in 4 patients. A renal biopsy was performed on 3 patients, revealing acute tubule interstitial nephritis (ATIN), karyomegalic interstitial nephritis, and acute tubular necrosis (ATN). ConclusionRenal toxicity represents a challenging adverse event that could negatively impact outcomes of metastatic nonsquamous NSCLC patients receiving CT/ICI demanding a multidisciplinary approach.

Brief Communication PD1-related Nephrotoxicity: Optimizing Its Clinical Management Through Histopathologic Features.

Immune-related nephrotoxicity (ir-N) is a rare adverse event of immune-checkpoint(s) inhibitors (ICI) therapy and its clinical management is still debated. Among 501 consecutive ICI-treated patients at our Institution, 6 who developed an ir-N with clinical signs suggestive for an acute kidney injury underwent kidney biopsy. Histology showed an acute tubule-interstitial nephritis, simulating the scenario of acute T-cell-mediated kidney transplant rejection. Thus, the management of allograft kidney rejection routinely utilized at our clinic was implemented, leading to rapid renal function improvement. Histologic features supporting the definition of an immune-mediated acute kidney injury in ICI-treated patients may help optimizing the clinical management of ir-N.

POS-022 ACUTE TUBULO-INTERSTITIAL NEPHRITIS WITH EOSINOPHILS, SUSPECTED TO BE DRUG-INDUCED, AS SEEN ON NATIVE KIDNEY BIOPSIES: 10-YEAR EXPERIENCE FROM AN INDEPENDENT CENTRAL PATHOLOGY LABORATORY IN KENYA

Drug-induced acute tubulointerstitial nephritis (ATIN) is a well-recognised cause of unexplained AKI that can lead to CKD. The presence of eosinophils in the tubulo-interstitial inflammation associated with ATI is considered a hallmark of the diagnosis. There is scarcity of data on biopsy-proven drug-induced ATIN in Africa. The author set out to establish the extent of biopsy-proven drug-induced ATIN in native kidney biopsies a 10-year period from his experience at a pathology central referral laboratory that handles the highest number of kidney biopsies in the region. Histopathology reports in text form were searched for key words “tubulo-interstitial nephritis” and respective cases identified were further examined to confirm those that were acute or active tubule-interstitial nephritis with eosinophils present, which were deemed to be in keeping with a diagnosis of drug-induced acute tubulo-interstitial nephritis. Associated pathological findings present in the biopsies were also recorded. The results were tabulated and tallied on Excel spreadsheet to obtain the summary statistics. A total of 34 cases of suspected drug-induced ATIN were identified representing 3.2% of all native kidney biopsies in the 10-year period. The cases were reported in each year except for 2014, with 2011-2013 having a case each, 2015 had 4 cases, 2016 had 5 cases, while 2017-2019 had 6 cases each and 2020 had 4 cases. An equal gender distribution was noted with ½ the cases being males and ½ being females. The youngest patient was 15 years old and the oldest 69 years old, the mean age at 39.2 years and median of 40 years. The degree of inflammation and acute kidney injury was mild in 14 cases (41%), similarly moderate in 14 cases (41%) and severe in 6 cases (18%), while concurrent chronic kidney damage was minimal in 16 cases (47%), mild in 5 cases (15%), moderate in 12 cases (35%) and severe in 1 case (3%). All but 4 cases (12%) had an associated pathological diagnostic finding, of which the commonest associated pathological finding was hypertensive changes of benign nephrosclerosis in 6 cases (18%), membranous glomerulopathy 6 cases (18%), diabetic nephropathy 4 cases (12%), lupus nephritis 4 cases (12%), two cases each of AL amyloidosis, HIVAN and IgA nephropathy, and a case each of AA amyloidosis, primary FSGS, ascending infection and malignancy. The majority of biopsy-proven cases of drug-induced ATIN seen at this independent central laboratory in Kenya are associated with other renal pathologies on the same respective biopsies, and only 12% had no related renal pathologies on the biopsies thus only a minority of cases were 'purely' drug-induced ATIN as the primary pathology. The exact medication linked to the drug-induced ATIN was not indicated in the clinical details. Interestingly, none of the cases was actually clinically suspected pre-biopsy to be drug-induced ATIN. Although rare, biopsy-proven drug-induced ATIN is a significant cause of AKI, and based on this analysis, it appears that most cases of drug-induced ATIN compound or exacerbate other underlying renal pathologies with underlying hypertensive kidney disease, membranous nephropathy and diabetic nephropathy as the commonest associated pathologies. ATIN needs to be born in mind by nephrologists when working up patients for AKI, and also born in mind by pathologists when examining kidney biopsies.

Renal Complications Related to Checkpoint Inhibitors: Diagnostic and Therapeutic Strategies.

Immune checkpoint inhibitors (ICI) targeting CTLA-4 and the PD-1/PD-L1 axis have unprecedentedly improved global prognosis in several types of cancers. However, they are associated with the occurrence of immune-related adverse events. Despite their low incidence, renal complications can interfere with the oncologic strategy. The breaking of peripheral tolerance and the emergence of auto- or drug-reactive T-cells are the main pathophysiological hypotheses to explain renal complications after ICI exposure. ICIs can induce a large spectrum of renal symptoms with variable severity (from isolated electrolyte disorders to dialysis-dependent acute kidney injury (AKI)) and presentation (acute tubule-interstitial nephritis in >90% of cases and a minority of glomerular diseases). In this review, the current trends in diagnosis and treatment strategies are summarized. The diagnosis of ICI-related renal complications requires special steps to avoid confounding factors, identify known risk factors (lower baseline estimated glomerular filtration rate, proton pump inhibitor use, and combination ICI therapy), and prove ICI causality, even after long-term exposure (weeks to months). A kidney biopsy should be performed as soon as possible. The treatment strategies rely on ICI discontinuation as well as co-medications, corticosteroids for 2 months, and tailored immunosuppressive drugs when renal response is not achieved.

Immune checkpoint inhibitors-induced nephropathy: a French national survey.

Immune checkpoint inhibitors (ICIs), aiming to foster cancer-targeted immune response, proved to be effective in several advanced malignancies at the price of immune-related adverse events affecting various organs, notably the kidneys. Herein, a retrospective descriptive analysis was performed on all biopsy-confirmed cases of ICI-induced nephropathy notified to the French Pharmacovigilance database to date. Data were gathered about patients' characteristics, acute kidney injuries and histopathological features. A total of 63 biopsy-proven cases were included for analysis. Immune-related nephropathy occurred after a mean of 105.5 ± 98.6 (standard deviation) days after the introduction of the ICI. Kidney Disease: Improving Global Outcomes acute kidney injury stage 3 occurred in 36.5% of patients, and the mean peak serum creatinine was 288µmol/L. Histopathology suggested acute tubule-interstitial nephritis in 52 patients (83%), while signs of acute tubular necrosis were found in 18 (29%) and glomerular involvement in 5 of them (8%). Another immune-related adverse event was documented in 25 patients (39.7%). Patients were treated with corticosteroids in 88.9% of cases. All in all, 27.0% fully recovered, 54.0% partially recovered, 12.7% did not recover. Rechallenge was attempted in 19 patients and one patient relapsed. Three-quarters of patients received a medication known to cause acute tubule-interstitial nephritis. The major limits of this study are those inherent to pharmacovigilance studies, such as its retrospective nature and incomplete data. Although it cannot pretend drawing any pathophysiological conclusion, this study depicts the clinical and histopathological pictures of ICI-induced nephropathies in a large cohort of biopsied patients with all grades of severity.

MO004PRIMARY BILIARY CHOLANGITIS PRESENTING WITH RENAL FANCONI SYNDROME: A FORGOTTEN PHENOTYPE

Abstract Background and Aims Primary biliary cholangitits (PBC) is an autoimmune liver disease, leading to liver fibrosis and cirrhosis. It is a rare disease affecting 1 in 3-4000 people and is more common in females. Symptoms may go unnoticed and include itch and fatigue. Most patients have anti-mitochondrial antibodies (AMA) as well as raised gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) levels. First line treatment for PBC is ursodeoxycholic acid and is usually continued lifelong. It improves liver biochemistry, histological progression of liver disease and liver transplant-free survival. Renal complications of PBC include distal renal tubular acidosis (RTA), tubule-interstitial nephritis (TIN) and renal Fanconi syndrome. Method We reviewed a case of PBC presenting with renal Fanconi syndrome. Results A 48-year-old female was referred to the renal clinic due to progressive decline in renal function since she was diagnosed with type 2 diabetes in 2007. She was also known to have AMA (&amp;gt;1:640) and previously had transient transaminitis. She was clinically well with no major symptoms but reported that she had had a few episodes of urinary tract infection in the previous year. Her diabetes was managed with lifestyle modifications in the past until a few months ago when Metformin was introduced. However, her HbA1c level had never been greater than 55 mmol/mol. Urine dipstick in the clinic showed pH of 6, blood+, glucose+++, protein+++ and ketone trace. The severity of glycosuria was inconsistent with her glycaemic control. There was a disparity between her urine albumin/creatinine ration (ACR) of 18.8g/mol and protein/creatinine ratio (PCR) of 124mg/mmol. Myeloma screen was negative and further urine analysis showed generalised aminoaciduria. She also had hypouricaemia, intermittent hypophosphataemia and non-anion gap metabolic acidosis. These results are in keeping with renal Fanconi syndrome. Her eGFR was 48 ml/min/1.72m2 in 2007 and was 21 ml/min/1.72m at the time of review. A renal biopsy was undertaken, and the appearances were suggestive of mild tubulo-interstitial nephritis; the glomeruli were unremarkable; there was mild chronic tubulo-interstitial damage. She was started on oral steroid, sodium bicarbonate and ursodeoxycholic acid. The course of steroid had a slight transitory beneficial effect on the renal function. Conclusion Distal RTA is the usual renal feature of PBC, occurring in 1/3 of cases with advanced disease. In contrast, proximal RTA associating with renal Fanconi syndrome occurs rarely. Like our case, the cases that have been previously reported show that Fanconi syndrome occurred during the early phase of PBC in the absence of marked hepatic abnormalities, and were associated with CKD. Fanconi syndrome and TIN are renal features of mitochondrial cytopathies and are perhaps a forgotten association of PBC. Antimitochondrial antibodies may play a role in the onset of tubulo-interstitial nephritis and Fanconi syndrome.

Acute Renal Failure Induced by Madder

Madder or Rubia Tincturium, called in Morocco ELFOUA is a plant belonging to the Rubiaceae family. Used in Morocco for its cosmetic food and therapeutic properties in particularly anemia and all blood diseases. It can be toxic if it is incorrectly dosed. We report 3 cases of nephrotoxicity collected in the nephrology and hemodialysis service of the IBNROCHD university hospital center in Casablanca: 3 women aged 15, 39 and 47 years, following the ingestion of infusion of this plant at doses indeterminate, presented with acute tubuleinterstitial nephritis. These new cases of nephrotoxicity at RUBIA TINCTURIUM must challenge the need to know how to evoke the diagnosis, to inform, to fight against the trivialization of its consumption, to encourage research on the traditional pharmacopoeia allowing to identify their therapeutic properties in order to formalize, rationalize and codify their prescriptions.

P1713A CASE OF DEVASTATING BARIATRIC SURGERY-RELATED ACUTE OXALATE NEPHROPATHY FIRST DIAGNOSED AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims Despite the obvious efficacy in achieving weight loss, traditional malabsorptive procedures (intestinal by-pass) used for the treatment of obesity, may be associated with enteric oxaluria. Enteric oxaluria, by causing calcium-oxalate stones and nephrocalcinosis, represents an under-recognized cause of end-stage kidney disease in patients with history of intestinal by-pass. Herein, we describe a patient with a long-standing history of intestinal by-pass who developed a devastating acute oxalate nephropathy first diagnosed after kidney transplantation. Method A white female aged 50, who started hemodialysis one year earlier because of tubule-interstitial nephritis on a kidney biopsy, and who had history of recurrent kidney stones (calcium oxalate), underwent urgent deceased-donor kidney transplantation because of exhausted vascular access for hemodialysis (tunneled CVC right giugular vein as the last resort). She had received intestinal by-pass surgery 20 yrs earlier, and had a pacemaker implantation in the left sublavian vein for AV block two years earlier. She was highly sensitized because of blood transfusions at the time of surgery. Results After transplantation, graft function had immediate recovery, serum creatinine decreasing to 2.0mg/dL (117 mmol/L) on post-operative day (POD) 3. Shortly after, serum creatinine started rising until it reached 4.0mg/dL (354mmol/L) on POD 5. Three graft biopsies (performed on POD 6, 9 and 15 post-transplant) revealed acute oxalate nephropathy ( Figure1-2 large oxalate crystals on fresh unfixed core of kidney tissue analyzed under bright field microscope using polarized light) with no sign of rejection. Serial monitoring of Luminex SAB did not reveal circulating anti-HLA donor specific antibodies. Fundus examination revealed two tiny mono-lateral retinal oxalate deposits, whereas bone biopsy did not reveal oxalate accumulation. Plasma oxalate levels were 43 mmol/L on POD 10 were urinary oxalate excretion was 29mg /day on POD 14. The patient slowly progressed to end-stage kidney disease 2-month post-transplantation despite daily high flux dialysis since POD 7, fat-free and oxalate-free diet, oral potassium and high dose pyridoxine supplements. Conclusion Patients on chronic dialysis with a previous history of bariatric surgery via intestinal by-pass may have oxalate nephropathy caused by enteric oxaluria as unknown primary renal disease. The disease may recur shortly after transplantation despite the adoption of prompt aggressive treatment for oxalate removal.

TO017CLINICAL CHARACTERISTICS AND INDEPENDENT PREDICTORS OF CHECK POINT INHIBITORS-ASSOCIATED AKI: WHAT DO WE KNOW?

Abstract Background and Aims Checkpoint inhibitors (CPI) are used to treat solid organ malignancies. CPI–associated acute renal injury (AKI) is an adverse effect of these therapies and its incidence is 13-29%. Clinical data on this complication is scarce. The aim of our study is to define clinical characteristics and risk factors of CPI-associated AKI. Method Clinical and demographic data of all patients receiving immunotherapy between March 2018 and May 2019 at our center were evaluated. Patients were divided into two groups depending on the development of AKI during the study period. AKI was defined according to AKIN classification. We compared clinical and demographic characteristics between these two groups and patients who developed mild AKI and severe AKI. Results During the study period, 821 patients received CPIs. Mean age 62.03±12.06 years and 486(59.2%) men. Malignancies were lung in 249 (30.3%), urogenital tract in 168 (20.5%), melanoma in 89 (10.8%) and others in 315 patients (38.4%). 446(54.3%) patients received anti-PD1, 230(28%) anti-PDL1, 13 (1.6%) anti-CTLA4, 36 (4.4%) received other drug and 96(11.7%) were treated with both anti-CTLA4 and anti-PD1 or anti.PDL1. Baseline creatinine was 0.85±0.30 mg/dL and 188 (22.9%) patients presented creatinine&amp;gt;1 mg/dL before starting CPI. 125 patients (15.2%) developed AKI during the study period, 85(68%) men and mean age 65.1±10.7 years. Baseline creatinine of these patients 0.97±0.45 mg/dL and 44 (35.2%) presented basal creatinine&amp;gt;1mg/dL. Mean creatinine at the diagnosis of AKI 2.27±1.34 mg/dL and two patients required haemodialysis. Leukocyturia was present in 21 patients(16.8%) and haematuria in 12 (9.6%). 5 patients presented AKI secondary to obstructive uropathy. Mean time from CPI initiation to AKI was 5.6±5.8 months. Of those 125 patients, 23 (18.4%) were referred to Nephrology and 9 (7.2%) underwent kidney biopsy. 1 patient presented endocapillar proliferative non-CPI related glomerulonephritis and 8 (6.4%) acute tubule-interstitial nephritis (ATIN). 23 (18.4%) patients were treated with corticosteroids. Mean creatinine at 6 months after AKI was 1.04±0.34 mg/dL (data from 45 patients) and 40 patients (data from 45 patients) showed complete recovery of kidney function at 6 months. Patients who developed a severe AKI stage 2 or 3 were more frequently women (41.8% vs 24.3%, p=0.03), had lower basal creatinine (0.86±0.25 vs 1.06±0.54 mg/dL, p=0.0130), showed and increased latency from CPI initiation to AKI (6.9±6 vs 4.5±5.5 months, p=0.0267) and presented worse recovery of kidney function at 6 months than patients with AKI stage 1(creatinine 6 months 1.18±0.40 mg/dL, p=0.0398 and complete recovery of kidney function at 6 months 70.5% vs 93.3%, p=0.0353). There was no association between the severity of AKI and type of CPI and type of malignance. When comparing patients who developed AKI with patients whit patient who did not, patients with AKI were older (65.1±10.7 vs 62.03±12.06 years old, p=0.0017), more frequently men (68% vs 57.9%), p=0.0296) and presented higher baseline creatinine (0.97±0.45 vs 0.85±0.30 mg/dL, p&amp;lt;0.0001), as well as more frequently a baseline creatinine &amp;gt; 1 mg/dL (35.2% vs 20.7%, p=0.0004). Type of CPI and type of malignance were not associated with the presence of AKI. Older age (OR 1.020, CI 95% 1.002-1.038) and baseline creatinine (OR 3.293, CI 95% 1.678-6.461) were identified as independent predictors of AKI development in our CPI treated patients Conclusion CPI-associated AKI incidence in our centre is 15.2%. Of them, 44% developed severe AKI. Only 18.4% were referred to a nephrologist and kidney biopsy performed in 7.2%. ATIN was the most common diagnosis. 18.4% received corticosteroids. Older age and higher baseline creatinine were identified as independent predictors for AKI development in patients with cancer CPI-treated. Patients developing a severe AKI showed worse kidney function at 6 months.

Spectrum of renal disease in HIV-infected children: report of five cases

There is a paucity of literature on renal diseases associated with HIV infection in Asian countries. Renal disease in HIV-infected children can involve the glomerulus, interstitium, tubules or blood vessels of the kidney. In this case series, five HIV-infected children with various forms of renal disease are reported. The renal pathology included HIV-associated nephropathy, collapsing focal segmental glomerulosclerosis without tubular changes, tubule-interstitial nephritis and minimal change disease (MCD). Case five fulfilled the classification criteria for childhood polyarteritis nodosa (PAN). It is important to screen all HIV-infected children for renal disease to enable detection at an early stage.

BK Virus nephropathy in living donor renal allograft recipients: An observational study from a large transplant center in India.

BK virus is a polyoma virus which remains in latent phase in the urinary tract, particularly in the renal tubular epithelial cells. In immunosuppressed patients, it is activated and manifests as tubule-interstitial nephritis causing renal allograft dysfunction. A total of 402 patients who underwent renal allograft biopsy from 2013 to 2016 were included in this study; six patients were diagnosed to have BK virus nephropathy. Histopathology showed ground glass intra-nuclear inclusions accompanied by acute tubular injury, interstitial inflammation, and varying degree of interstitial fibrosis and tubular atrophy. Patients were managed with reduction in the overall immunosuppression. Only one patient progressed to graft failure on follow-up. The overall prevalence of polyoma virus at our center is 1.49%.

The Unusually Complicated Wasp Stings

Wasp stings can cause severe morbidity and mortality. Anaphylaxis, acute kidney injury, multi organ dysfunction and uncommonly nervous system involvement are some of important complications of wasp stings. We report a rare case of wasp stings complicated by acute kidney injury due to possible acute tubule interstitial nephritis and intracerebral hemorrhage in the absence of aneurysm of vessels and coagulation abnormalities.

Nefritis túbulo intersticial por leflunomida

The link between renal Tubule Interstitial Nephritis and the use of Leflunomide has not been described in the literature yet, this drug is not recognized as a nephrotoxic; therefore tracking renal function is not usually performed. We report the case of a patient admitted to the University Hospital of Clinic San Rafael by non-specific clinical symptoms and rapid deterioration of renal function. After ruling out the usual causes, we performed a renal biopsy, documenting the presence of severe tubule interstitial nephritis. By the time the use of Leflunomide was the only unusual precedent. After we suspended the treatment, the patient showed full recovery of the renal function. It is our intention to describe this case to highlight the connection between renal Tubule Interstitial Nephritis and the use of Leflunomide in order to promote keeping track of similar cases.

Ultrasound findings of BK polyomavirus-associated nephropathy in renal transplant patients.

BK polyomavirus (BKV) is an emerging pathogen in immunocompromised patients. BKV infection occurs in 1-9% of renal transplants and causes chronic nephropathy or graft loss. Diagnosis of BKV-associated nephropathy (BKVAN) is based on detection of viruria then viremia and at least a tubule-interstitial nephritis at renal biopsy. This paper describes the ultrasound and color Doppler (US-CD) features of BKVAN. Seventeen patients affected by BKVAN were studied using a linear bandwidth 7-12MHz probe. Ultrasound showed a widespread streak-like pattern with alternating normal echoic and hypoechoic streaks with irregular edges from the papilla to the cortex. Renal biopsy performed in hypoechoic areas highlighted the typical viral inclusions in tubular epithelial cells. Our experience suggests a possible role for US-CD in the non-invasive diagnosis of BKVAN when combined with blood and urine screening tests. US-CD must be performed with a high-frequency linear probe to highlight the streak-like pattern of the renal parenchyma.

Administration of α-Galactosylceramide Improves Adenine-Induced Renal Injury.

Natural killer T (NKT) cells are a subset of lymphocytes that reacts to glycolipids presented by CD1d. Invariant NKT cells (iNKT) correspond to >90% of the total population of NKTs and reacts to α-galactosylceramide (αGalCer). αGalCer promotes a complex mixture of Th1 and Th2 cytokines, as interferon (IFN)-γ and interleukin (IL)-4. NKT cells and IFN-γ are known to participate in some models of renal diseases, but further studies are still necessary to elucidate their mechanisms. The aim of our study was to analyze the participation of iNKT cells in an experimental model of tubule-interstitial nephritis. We used 8-wk-old C57BL/6j, Jα18KO and IFN-γKO mice. They were fed a 0.25% adenine diet for 10 d. Both adenine-fed wild-type (WT) and Jα18KO mice exhibited renal dysfunction, but adenine-fed Jα18KO mice presented higher expression of kidney injury molecule-1 (KIM-1), tumor necrosis factor (TNF)-α and type I collagen. To analyze the role of activated iNKT cells in our model, we administered αGalCer in WT mice during adenine ingestion. After αGalCer injection, we observed a significant reduction in serum creatinine, proinflammatory cytokines and renal fibrosis. However, this improvement in renal function was not observed in IFN-γKO mice after αGalCer treatment and adenine feeding, illustrating that this cytokine plays a role in our model. Our findings may suggest that IFN-γ production is one of the factors contributing to improved renal function after αGalCer administration.

Adverse events: ART and the kidney: alterations in renal function and renal toxicity.

Renal dysfunction is common in HIV-positive patients who receive antiretroviral therapy (ART). Several antiretrovirals have been associated with kidney disease progression, inhibition of renal tubular transporters that mediate creatinine secretion or impaired reabsorption of phosphate and low-molecular weight proteins. These aberrations of renal function are typically non-treatment limiting and of unclear clinical significance. By contrast, severe renal toxicity is infrequent in well-managed patents. Tenofovir-DF and atazanavir may cause acute tubular injury, tubule-interstitial nephritis or nephrolithiasis. Discontinuation of the offending drug is required to mitigate the adverse effects on kidney or bone. This presentation will discuss ART-associated changes in renal function and treatment-limiting renal toxicity in terms of incidence, risk factors, putative mechanism and provide recommendations for clinical practice.

Macrophage trafficking as key mediator of adenine-induced kidney injury.

Macrophages play a special role in the onset of several diseases, including acute and chronic kidney injuries. In this sense, tubule interstitial nephritis (TIN) represents an underestimated insult, which can be triggered by different stimuli and, in the absence of a proper regulation, can lead to fibrosis deposition. Based on this perception, we evaluated the participation of macrophage recruitment in the development of TIN. Initially, we provided adenine-enriched food to WT and searched for macrophage presence and action in the kidney. Also, a group of animals were depleted of macrophages with the clodronate liposome while receiving adenine-enriched diet. We collected blood and renal tissue from these animals and renal function, inflammation, and fibrosis were evaluated. We observed higher expression of chemokines in the kidneys of adenine-fed mice and a substantial protection when macrophages were depleted. Then, we specifically investigated the role of some key chemokines, CCR5 and CCL3, in this TIN experimental model. Interestingly, CCR5 KO and CCL3 KO animals showed less renal dysfunction and a decreased proinflammatory profile. Furthermore, in those animals, there was less profibrotic signaling. In conclusion, we can suggest that macrophage infiltration is important for the onset of renal injury in the adenine-induced TIN.