Distinct developmental reprogramming footprint of macrophages during acute kidney injury across species.

Acute kidney injury (AKI) is a common finding in hospitalized patients, particularly those who are critically ill. The development of AKI is associated with several adverse outcomes including mortality, morbidity, progression to chronic kidney disease, and an increase in healthcare expenditure. Despite the well-established negative impact of AKI and rigorous efforts to better define, identify, and implement targeted therapies, the overall approach to the treatment of AKI continues to principally encompass supportive measures. This enduring challenge is primarily due to the heterogeneous nature of insults that activate many independent and overlapping molecular pathways. Consequently, it is evident that the identification of common mechanisms that mediate the pathogenesis of AKI, independent of etiology and engaged pathophysiological pathways, is of paramount importance and could lead to the identification of novel therapeutic targets. To better distinguish the commonly modulated mechanisms of AKI, we explored the transcriptional characteristics of human kidney biopsies from patients with acute tubular necrosis (ATN), and acute interstitial nephritis (AIN) using a NanoString inflammation panel. Subsequently, we used publicly available single-cell transcriptional resources to better interpret the generated transcriptional findings. Our findings identify robust acute kidney injury (AKI-induced) developmental reprogramming of macrophages (MΦ) with the expansion of C1Q+, CD163+ MΦ that is independent of the etiology of AKI and conserved across mouse and human species. These results would expand the current understanding of the pathophysiology of AKI and potentially offer novel targets for additional studies to enhance the translational transition of AKI research.NEW & NOTEWORTHY Our findings identify robust acute kidney injury (AKI)-induced developmental reprogramming of macrophages (MΦ) with the expansion of C1Q+, CD163+ MΦ that is independent of the etiology of AKI and conserved across mouse and human species.

Daily dose of metformin caused acute kidney injury with lactic acidosis: a case report.

BACKGROUND: Metformin-induced lactic acidosis with acute kidney injury is rare but well known. Here we report a case of a Japanese patient taking metformin who experienced severe acute renal failure accompanied with significantly elevated metformin plasma concentrations and signs of lactic acidosis. CASE PRESENTATION: A 60-year-old Japanese man with type II diabetes, who was taking metformin (500 mg three times a day) along with several other medications, visited the emergency department with dizziness, malaise, and oliguria. The initial laboratory test results showed elevated levels of serum creatinine and blood urea nitrogen, although his renal function was normal approximately 2 weeks earlier. His lactate level was raised (4.27 mmol/L), and he was diagnosed with lactic acidosis. Considering the low creatinine clearance and elevated urinary albumin/serum creatinine ratio, urinary N-acetyl-ß-D-glucosaminidase level, and ß2-microglobulin level, the patient was further diagnosed with AKI (in other words, acute tubular necrosis). A renal biopsy performed on day 3 after admission revealed renal tubular epithelium necrosis, supporting this diagnosis. The patient underwent intermittent hemodialysis until he was discharged on day 13. The metformin concentrations on days 3, 5, and 7 were 8.95, 2.58, and 0.16 µg/mL, respectively, which is significantly higher than the maximal steady-state concentration of metformin at the recommended dosage (approximately 1 µg/mL). The calculated pharmacokinetic parameters of metformin suggested poor renal excretion and a low distribution volume at higher metformin levels. Other possible acute kidney injury-causing factors included dehydration, alcohol consumption, and the use of an angiotensin receptor blocker or SGLT2 inhibitor. CONCLUSIONS: This is the first reported case of acute kidney injury possibly caused by high levels of metformin with lactic acidosis in a patient treated with the recommended metformin dose. Thus, the development of metformin-induced acute kidney injury should be considered for patients with several acute kidney injury risk factors who are taking metformin.

Biopsy-proven first dose of oxaliplatin-induced acute tubular necrosis leading to end-stage renal failure: a case report.

BACKGROUND: Oxaliplatin is an anticancer therapy for pancreatic, gastric, and colorectal cancers. It is also used in patients with carcinomas of unknown primary sites. Oxaliplatin is associated with less frequent renal dysfunction than other conventional platinum-based drugs such as cisplatin. Albeit, there have been several reports of acute kidney injury with frequent use. In all cases, renal dysfunction was temporary and did not require maintenance dialysis. There have been no previous reports of irreversible renal dysfunction after a single dose of oxaliplatin. CASE PRESENTATION: Previous reports of oxaliplatin-induced renal injury occurred after patients received multiples doses. In this study, a 75-year-old male with unknown primary cancer and underlying chronic kidney disease developed acute renal failure after receiving the first dose of oxaliplatin. Suspected of having drug-induced renal failure through an immunological mechanism, the patient was treated with steroids; however, treatment was ineffective. Renal biopsy ruled out interstitial nephritis and revealed acute tubular necrosis. Renal failure was irreversible, and the patient subsequently required maintenance hemodialysis. CONCLUSIONS: We provide the first report of pathology-confirmed acute tubular necrosis after the first dose of oxaliplatin which led to irreversible renal dysfunction and maintenance dialysis.

Pathological Features of Recovery or Progression in Acute Tubular Necrosis: Single Centre Study.

Acute tubular necrosis (ATN) is the most important and frequent cause of acute kidney injury (AKI). Controversy exists concerning the role of renal biopsy in the evaluation of ATN prognosis. We aim in our study to evaluate the role of renal biopsy for the detection of recovery and progression and rate of recovery of ATN. The study was designed to include all biopsies with the diagnosis in ATN in adults >21-year-old, from January 2016 to December 2018. Biopsies were recruited retrospectively and were reviewed by three pathologists and quantitated. Four histological ATN features were evaluated. Flattening cells, distension or dilatation, debris, and vacuolation and for each a score were attributed as follows: 0 = less than 5% of section, 1 = 6%-25%, 2 = 26%-50%, 3 = >50%. Thirty-five patients with 35 renal biopsies were analyzed. Flattening was seen <5% in nine patients, 6%-25% in 15 patients, 26%-50% in six patients. and >50% in five patients. Dilatation was seen <5% in 11 patient, 6%-25% in 10 patients, 26%-50% seen in six patients, and >50% in eight patients. The presence of debris was seen in <5% in 12 patients, 6%-25% in 12 patients, 26%-50% seen in six patients, and >50% seen in five patient. Vacuolation was seen in 5% in eight patients, 6%-25% in 14 patients, 26%-50% in seven patients, and >50% in six patients. It was found that flattening <5% and dilatation <5% and dilatation >50% in renal biopsy are the good indicators for recovery and good prognosis of cases of ATN, in addition debris <5% and >50% and vacuolation <5% are also good indicators for recovery and good prognosis of cases of ATN. On the other hand, flattening from 6% to 25% and from 26% to 50%, dilatation from 6% to 25%, debris from 26% to 50% and vacuolation >50% are also indicators for delayed recovery and poor prognosis of cases of ATN. Renal biopsy in AKI with the diagnosis of ATN with scoring system of flattening, dilatation, debris, and vacuolation can point to indication of recovery or progression of these cases.

Monitoring intracellular tacrolimus concentrations and its relationship with rejection in the early phase after renal transplantation.

INTRODUCTION: After kidney transplantation, rejection and drug-related toxicity occur despite tacrolimus whole-blood pre-dose concentrations ([Tac]blood) being within the target range. The tacrolimus concentration within peripheral blood mononuclear cells ([Tac]cells) might correlate better with clinical outcomes. The aim of this study was to investigate the correlation between [Tac]blood and [Tac]cells, the evolution of [Tac]cells and the [Tac]cells/[Tac]blood ratio, and to assess the relationship between tacrolimus concentrations and the occurrence of rejection. METHODS: In this prospective study, samples for the measurement of [Tac]blood and [Tac]cells were collected on days 3 and 10 after kidney transplantation, and on the morning of a for-cause kidney transplant biopsy. Biopsies were reviewed according to the Banff 2019 update. RESULTS: Eighty-three [Tac]cells samples were measured of 44 kidney transplant recipients. The correlation between [Tac]cells and [Tac]blood was poor (Pearson's r = 0.56 (day 3); r = 0.20 (day 10)). Both the dose-corrected [Tac]cells and the [Tac]cells/[Tac]blood ratio were not significantly different between days 3 and 10, and the median inter-occasion variability of the dose-corrected [Tac]cells and the [Tac]cells/[Tac]blood ratio were 19.4% and 23.4%, respectively (n = 24). Neither [Tac]cells, [Tac]blood, nor the [Tac]cells/[Tac]blood ratio were significantly different between patients with biopsy-proven acute rejection (n = 4) and patients with acute tubular necrosis (n = 4) or a cancelled biopsy (n = 9; p > 0.05). CONCLUSION: Tacrolimus exposure and distribution appeared stable in the early phase after transplantation. [Tac]cells was not significantly associated with the occurrence of rejection. A possible explanation for these results might be related to the low number of patients included in this study and also due to the fact that PBMCs are not a specific enough matrix to monitor tacrolimus concentrations.

[Kidney damage in COVID-19]. / Les atteintes rénales de la COVID-19.

COVID-19 is a disease caused by the RNA virus SARS-CoV-2. It is characterised by an attack mainly affecting the respiratory system. There is renal involvement which is characterised by three main types of damage, acute tubular necrosis occurring in the most severe cases, proximal tubulopathy which is a prognostic marker of the disease and segmental and focal hyalinosis occurring in a genetically predisposed terrain. The pathophysiology of SARS-CoV-2 renal involvement is not yet defined. The direct role of the virus is debated, whereas the cytokine storm and the hypoxic and thrombotic complications seem more important. The long-term outcome of the renal damage appears to be quite good. Long-term follow-up will allow us to say whether the renal damage is part of the long COVID.

Renal Considerations in COVID-19: Biology, Pathology, and Pathophysiology.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged into a worldwide pandemic of epic proportion. Beyond pulmonary involvement in coronavirus disease 2019 (COVID-19), a significant subset of patients experiences acute kidney injury. Patients who die from severe disease most notably show diffuse acute tubular injury on postmortem examination with a possible contribution of focal macro- and microvascular thrombi. Renal biopsies in patients with proteinuria and hematuria have demonstrated a glomerular dominant pattern of injury, most notably a collapsing glomerulopathy reminiscent of findings seen in human immunodeficiency virus (HIV) in individuals with apolipoprotein L-1 (APOL1) risk allele variants. Although various mechanisms have been proposed for the pathogenesis of acute kidney injury in SARS-CoV-2 infection, direct renal cell infection has not been definitively demonstrated and our understanding of the spectrum of renal involvement remains incomplete. Herein we discuss the biology, pathology, and pathogenesis of SARS-CoV-2 infection and associated renal involvement. We discuss the molecular biology, risk factors, and pathophysiology of renal injury associated with SARS-CoV-2 infection. We highlight the characteristics of specific renal pathologies based on native kidney biopsy and autopsy. Additionally, a brief discussion on ancillary studies and challenges in the diagnosis of SARS-CoV-2 is presented.

Urinary NGAL as a Diagnostic and Prognostic Marker for Acute Kidney Injury in Cirrhosis: A Prospective Study.

INTRODUCTION: Urinary neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in differentiating acute tubular necrosis (ATN) from other types of acute kidney injuries (AKIs) in cirrhosis, particularly hepatorenal syndrome (HRS). However, NGAL is not currently available in clinical practice in North America. METHODS: Urinary NGAL was measured in a prospective cohort of 213 US hospitalized patients with decompensated cirrhosis (161 with AKI and 52 reference patients without AKI). NGAL was assessed for its ability to discriminate ATN from non-ATN AKI and to predict 90-day outcomes. RESULTS: Among patients with AKI, 57 (35%) had prerenal AKI, 55 (34%) had HRS, and 49 (30%) had ATN, with a median serum creatinine of 2.0 (interquartile range 1.5, 3.0) mg/dL at enrollment. At an optimal cutpoint of 244 µg/g creatinine, NGAL distinguished ATN (344 [132, 1,429] µg/g creatinine) from prerenal AKI (45 [0, 154] µg/g) or HRS (110 [50, 393] µg/g; P < 0.001), with a C statistic of 0.762 (95% confidence interval 0.682, 0.842). By 90 days, 71 of 213 patients (33%) died. Higher median NGAL was associated with death (159 [50, 865] vs 58 [0, 191] µg/g; P < 0.001). In adjusted and unadjusted analysis, NGAL significantly predicted 90-day transplant-free survival (P < 0.05 for all Cox models) and outperformed Model for End-Stage Liver Disease score by C statistic (0.697 vs 0.686; P = 0.04), net reclassification index (37%; P = 0.008), and integrated discrimination increment (2.7%; P = 0.02). DISCUSSION: NGAL differentiates the type of AKI in cirrhosis and may improve prediction of mortality; therefore, it holds potential to affect management of AKI in cirrhosis.

Renal hemosiderosis presenting with acute kidney Injury and macroscopic hematuria in Immunoglobulin A nephropathy: a case report.

BACKGROUND: Macroscopic hematuria-associated acute kidney injury (AKI) is a well-known complication of immunoglobulin A (IgA) nephropathy. In such cases, intratubular obstruction by red blood cell (RBC) casts and acute tubular necrosis are mainly observed pathologically. Herein, we report the case of a patient with IgA nephropathy presenting with AKI following an episode of macrohematuria. The patient presented with severe renal tubular hemosiderosis and acute tubular necrosis and without any obvious obstructive RBC casts. CASE PRESENTATION: A 68-year-old woman, who was diagnosed with IgA nephropathy on renal biopsy 6 years ago, was admitted to our hospital after an episode of macroscopic glomerular hematuria and AKI following upper respiratory tract infection. Renal biopsy showed mesangial proliferation of the glomeruli, including crescent formation in 17 % of the glomeruli, and acute tubular necrosis without obvious hemorrhage or obstructive RBC casts. The application of Perls' Prussian blue stain showed hemosiderin deposition in the renal proximal tubular cells. Immunofluorescence showed granular mesangial deposits of IgA and C3. Based on these findings, she was diagnosed with acute tubular necrosis with a concurrent IgA nephropathy flare-up. Moreover, direct tubular injury by heme and iron was considered to be the cause of AKI. She was treated with intravenous pulse methylprednisolone followed by oral prednisolone. Thereafter, the gross hematuria gradually faded, and her serum creatinine levels decreased. CONCLUSIONS: IgA nephropathy presenting with acute kidney injury accompanied by macrohematuria may cause renal hemosiderosis and acute tubular necrosis without obstructive RBC casts. Hemosiderosis may be a useful indicator for determining the pathophysiology of macroscopic hematuria-associated AKI. However, renal hemosiderosis may remain undiagnosed. Thus, Perls' Prussian blue iron staining should be more widely used in patients presenting with hematuria.

The Role of Renal Pathology in the Prognosis and Recovery of Community-Acquired Acute Kidney Injury.

OBJECTIVES: The determinants leading to different renal outcomes in community-acquired acute kidney injury (CA-AKI) and the influence of renal histological damage on the prognosis and recovery of CA-AKI are scarcely reported. METHODS: Adult patients with CA-AKI admitted to Shanghai Changzheng Hospital with renal biopsy profiles from January 1, 2010, to December 31, 2018, were enrolled in our cohort. After 3 months of follow-up, clinical outcomes, including patient survival, dialysis requirement during hospitalization and at 3 months, CKD stage 3-5, and renal functional recovery at 3 months, were analyzed, and risk factors were identified. RESULTS: A total of 294 patients with CA-AKI with renal pathology were identified for this cohort. Among 282 patients who survived 3 months after AKI, 59.6% completely recovered, 21.3% partially recovered, 21.3% progressed to stage 3-5 CKD without dialysis, and 17.7% maintained dialysis. Moreover, 70.4% of patients in the cohort presented with de novo intrinsic renal disease, except acute tubular necrosis or acute interstitial nephritis, on renal biopsy. In the multivariate analyses, clinical factors were more related to short-term outcomes and severity of CA-AKI, represented by mortality, in-hospital dialysis, and CRRT requirement, while pathological elements were more involved with CKD progression, including dialysis-dependent or stage 3-5 CKD, and renal function recovery at the 3-month follow-up. The detrimental influence of glomerular and arterial lesions on renal prognosis of CA-AKI was as critical as tubular and interstitial lesions. CONCLUSIONS: Clinical and pathological parameters both contribute to patient and renal outcomes after CA-AKI. The value of renal biopsy should be recognized in prognostic prediction.

Outcomes of Delayed Graft Function in Kidney Transplant Recipients Stratified by Histologic Biopsy Findings.

Delayed graft function (DGF) after kidney transplantation is associated with an increased risk of graft failure. We studied the histologic findings among adult kidney transplant recipients transplanted between January 2000 and June 2015 who had DGF and had a kidney biopsy within 14 days of transplant. Death censored graft failure (DCGF) and death at 1 and 3 years after transplant were examined. A total of 269 transplant recipients fulfilled our selection criteria, of which 152 (56.51%) had acute tubular necrosis (ATN), 44 (16.4%) had acute rejection (AR), mainly T-cell mediated rejection (n = 31), 35 (13%) had ATN with AR (mainly T-cell mediated rejection, n = 26), and 38 (14.1%) had other pathology. Compared with those with ATN alone, kidney transplant recipients with AR alone had a significantly higher risk of DCGF at 1 year post transplant (adjusted hazard ratio = 3.70; 95% confidence interval 1.5-9.5; P = .006). Those with AR alone had an increased risk of DCGF at 3 years post transplant (hazard ratio = 3.10; 95% confidence interval 1.3-8.5; P = .01) in crude analyses. There was no association between DGF etiology and mortality. Early renal biopsy can be used to distinguish AR, which has protocolized treatments, from other etiologies. This could potentially alter allograft survival within 1 year of transplant complicated by DGF.

Lansoprazole promotes cisplatin-induced acute kidney injury via enhancing tubular necroptosis.

Acute kidney injury (AKI) is the main obstacle that limits the use of cisplatin in cancer treatment. Proton pump inhibitors (PPIs), the most commonly used class of medications for gastrointestinal complications in cancer patients, have been reported to cause adverse renal events. However, the effect of PPIs on cisplatin-induced AKI remains unclear. Herein, the effect and mechanism of lansoprazole (LPZ), one of the most frequently prescribed PPIs, on cisplatin-induced AKI were investigated in vivo and in vitro. C57BL/6 mice received a single intraperitoneal (i.p.) injection of cisplatin (18 mg/kg) to induce AKI, and LPZ (12.5 or 25 mg/kg) was administered 2 hours prior to cisplatin administration and then once daily for another 2 days via i.p. injection. The results showed that LPZ significantly aggravated the tubular damage and further increased the elevated levels of serum creatinine and blood urea nitrogen induced by cisplatin. However, LPZ did not enhance cisplatin-induced tubular apoptosis, as evidenced by a lack of significant change in mRNA and protein expression of Bax/Bcl-2 ratio and TUNEL staining. Notably, LPZ increased the number of necrotic renal tubular cells compared to that by cisplatin treatment alone, which was further confirmed by the elevated necroptosis-associated protein expression of RIPK1, p-RIPK3 and p-MLKL. Furthermore, LPZ deteriorated cisplatin-induced inflammation, as revealed by the increased mRNA expression of pro-inflammatory factors including, NLRP3, IL-1ß, TNF-α and caspase 1, as well as neutrophil infiltration. Consistently, in in vitro study, LPZ increased HK-2 cell death and enhanced inflammation, compared with cisplatin treatment alone. Collectively, our results demonstrate that LPZ aggravates cisplatin-induced AKI, and necroptosis may be involved in the exacerbation of kidney damage.

[Therapeutics for acute tubular necrosis in 2020]. / Prise en charge de la nécrose tubulaire aiguë en 2020.

Acute kidney injury is a major cause of in-hospital morbidity and mortality because of the serious nature of the underlying illnesses and the high incidence of complications. The two major causes of acute kidney injury that occur in the hospital are prerenal disease and acute tubular necrosis. Acute tubular necrosis has a histological definition, even if a kidney biopsy is rarely performed. Kidney injuries occurring during acute tubular necrosis are underlined by different pathophysiological mechanisms that emphasize the role of hypoxia on the tubular cells such as apoptosis, cytoskeleton disruption, mitochondrial function and the inflammation mediated by innate immune cells. The microcirculation and the endothelial cells are also the targets of hypoxia-mediated impairment. Repair mechanisms are sometimes inadequate because of pro-fibrotic factors that will lead to chronic kidney disease. Despite all the potential therapeutic targets highlighted by the pathophysiological knowledge, further works remain necessary to find a way to prevent these injuries.

Activity and short-term outcomes of kidney transplantation during the COVID-19 pandemic. / Actividad y resultados a corto plazo del trasplante renal durante la pandemia COVID-19.

INTRODUCTION: During the COVID-19 pandemic, the national transplant activity has been reduced due to the overload of the health system and concern for patient safety in this situation. The aim of our work is to expose the activity of kidney transplantation in Cantabria during the state of alarm, as well as to assess the safety of the transplantation program. MATERIAL AND METHODS: Retrospective study of kidney transplants performed in our Center from the beginning of the state of alarm until the beginning of the lockdown easing in Cantabria. Descriptive analysis of the demographic data of recipients and their donors, intraoperative data and postoperative outcomes. Comparative analysis with the data of the same period in 2017-2019, by means of the χ2 for categorical variables, Student's T and Mann-Whitney U tests in case of quantitative variables of normal and non-normal distribution, respectively. RESULTS: Fifteen kidney transplants were performed in the period described. Delayed renal function (DRF) was seen in 7.5% of patients, and 26.6% showed data of acute rejection; no patient presented COVID-19 disease. Comparative analysis showed a remarkable increase in the number of transplants in comparison with previous periods (15 vs 5.6), at the expense of donors from outside Cantabria (93.3%). We found no statistically significant differences in terms of cold ischemia time (p=0.77), DRF (p=0.73), need for dialysis (p=0.54), or appearance of post-surgical complications (p=0.61). CONCLUSIONS: The evolution of the pandemic in our region, and the adoption of strict protective measures has allowed the early and safe resumption of the renal transplantation program, increasing the number of transplants performed compared to previous years and maintaining comparable early post-operative results.

Nefropatía por tóxicos: la cocaína y su potente daño renal / Toxic nephropathy: cocaine and its potent kidney damage

Resumen El consumo de sustancias ilícitas en menores de 16 años y en adultos jóvenes se incrementa cada día en Colombia, por lo cual se presentan complicaciones asociadas que sería inusual encontrar en este grupo poblacional. El presente reporte de caso muestra cómo el uso de cocaína llevó a un paciente joven a desarrollar daño renal agudo con requerimiento de terapia de reemplazo renal, lo que en los hallazgos histológicos puede corresponder a una glomerulonefritis rápidamente progresiva o a una enfermedad tubulointersticial tipo necrosis tubular aguda o nefritis intersticial aguda.

Abstract In Colombia, the consumption of illicit substances increases daily. The increase and related consumption in the population involves both young people under 16 and young adults. Therefore, there are complications associated with the consumption of these substances that otherwise, would be unusual to find in this population group. In this case report, we will review how the use of cocaine led a young patient to the development acute kidney injury requiring renal replacement therapy, which in the histological findings may correspond to rapidly progressive glomerulonephritis, or tubulointerstitial disease either acute renal tubular necrosis or acute interstitial nephritis.

Investigating the threshold for early renal allograft biopsy: A South African single-centre perspective.

BACKGROUND: The most common clinical indication for renal biopsy in the early post-transplant period is early graft dysfunction (EGD), which may present either as delayed graft function (DGF) or acute graft dysfunction. Even though it is a valuable diagnostic tool, renal allograft biopsy is not without risk of major complications. Recent studies have suggested that, with modern immunosuppressive induction regimens and more accurate ways to determine high immunological risk transplants, early acute rejection (AR) is uncommon and routine biopsy for EGD does not result in a change in management. OBJECTIVES: To describe the histological findings and complications of renal allograft biopsies for EGD in our setting, and to determine whether our current threshold for biopsy is appropriate. METHODS: This study was a retrospective audit that included all patients who underwent renal allograft biopsy within the first 30 days of transplantation at Groote Schuur Hospital, Cape Town, South Africa, from 1 June 2010 to 30 June 2018. The indication for biopsy was any patient who showed significant EGD, characterised by acute graft dysfunction or DGF with dialysis dependence. RESULTS: During the study period, 330 patients underwent renal transplantation, of whom 105 (32%) had an early biopsy and were included in the study. The median age of recipients was 39 (range 17 - 62) years, with 65% males and 35% females. The majority of donors were deceased donations after brain death (70%), with an overall median cold ischaemic time of 9 hours (interquartile range (IQR) 4 - 16). The average number of human leukocyte antigen mismatches was 5 (IQR 4 - 7). A donor-specific antibody was recorded for 18% of recipients and a panel-reactive antibody score of >30% was recorded for 21%. The median duration after transplant for biopsy was 8 (IQR 6 - 10) days. During the first month of EGD, AR was diagnosed in 42% of patients who underwent biopsies. In 21% of these patients, there was acute cellular rejection, in 16% antibody-mediated rejection, and in 5% both of these. Acute tubular necrosis was the primary finding in 32%, with acute interstitial nephritis in 8%, and acute calcineurin toxicity in 4% of cases. A significant biopsy-related complication was recorded in 3 patients: 1 small-bowel perforation repaired via laparotomy, and 2 vascular injuries successfully embolised by interventional radiology. CONCLUSIONS: Considering the relative safety and high rate of detection of AR, a liberal approach to renal biopsy for EGD remains justifiable in our setting.

Urinary cytology: a potential tool for differential diagnosis of acute kidney injury in patients with nephrotic syndrome.

OBJECTIVE: Acute tubular necrosis (ATN) is a frequent cause of acute kidney injury (AKI). In patients with nephrotic syndrome (NS), AKI demands the differential diagnosis between ATN and rapidly progressive glomerulonephritis. In some cases, conclusive diagnosis is possible only by kidney biopsy. We aimed to study the potential use of urine cytology in the differential diagnosis between ATN and proliferative glomerular lesion in patients with NS. RESULTS: Cell size analysis showed a higher proportion of small cells and a lower proportion of large cells in the urine of patients with AKI. Cells phenotypes were easily defined using cytological preparations. Leukocytes were found to be a primary classifier of NS groups, with higher number in patients with AKI and patients with proliferative glomerular lesions. Although renal biopsy is still required for confirmative diagnosis, our data suggests that urinary cytology can be readily performed and support the differential diagnosis between proliferative glomerular lesion and ATN in patients with NS and AKI.

Parvovirus B19 infection and kidney injury: report of 4 cases and analysis of immunization and viremia in an adult cohort of 100 patients undergoing a kidney biopsy.

BACKGROUND: The seroprevalence of human Parvovirus B19 (PVB19) is 70-85% in adults worldwide. PVB19 is the etiologic agent of the fifth disease, is a cause of aplastic anemia, and can be associated with kidney injury. We aimed to describe the cases of 4 patients with kidney injury related to PVB19 primary infection, and to evaluate the seroprevalence of PVB19 and the incidence of PVB19 primary infection in patients undergoing a native kidney biopsy. METHODS: Cases of PVB19 infection with kidney injury were reviewed from the archives of the department of Nephrology. A systematic screening of anti-PVB19 IgG and IgM antibodies and viral DNA was performed in sera from 100 consecutive patients with a kidney biopsy in 2017-2018. RESULTS: The 4 patients with PVB19 infection-associated kidney disease displayed: one lupus-like glomerulonephritis (GN) without lupus auto-antibodies, one minimal change disease with tubular necrosis, one secondary hemolytic and uremic syndrome and one membrano-proliferative GN. In the 100 patients biopsied, 67 had elevated anti-PVB19 IgG, among whom 8 had elevated IgM, without circulating viral DNA, without any particular renal pathological pattern. One additional patient showed a seroconversion at the time of kidney biopsy, which revealed a class V lupus nephritis. CONCLUSION: PVB19 primary infection can be associated with different kidney diseases. The seroprevalence of PVB19 among patients with a kidney biopsy is similar to the overall population, and primary infection is rarely documented (1%) after systematic screening. Whether PV19 is nephrotoxic, or triggers renal endothelial injury and immune activation, remains to be elucidated.