Immunohistochemical Evaluation of Renal Biopsy with Anti-PD1 and p53 to Solve the Dilemma between Platinum- and Pembrolizumab-Induced AKI: Case Report and Review.

Introduction: The combination therapy of platinum and pembrolizumab looks like a promising treatment in advanced non-small-cell lung cancer. However, both platinum-based chemotherapy and pembrolizumab can lead to AKI. AKI can occur due to acute tubular necrosis or interstitial nephritis. It is essential to identify the drug responsible for renal damage. For this purpose, we used new immunohistochemistry markers (p53 and anti-PD1 analysis). Case Description: A 77-year-old female patient with advanced non-small-cell lung cancer received the PD-1 inhibitor pembrolizumab and platinum-based chemotherapy carboplatin. The patient, after 60 days, experienced AKI. A kidney biopsy was performed, and two new immunohistochemical techniques for p53 (experimental markers of ATN from platinum) and anti-PDL1 (experimental markers of PD-1 inhibitors nephritis) were employed. Renal biopsies revealed severe tubular damage. No infiltration was detected, and the immunohistochemical assessment of PDL-1 was negative. The expression of p53 was positive. The renal biopsy suggested platinum-induced acute tubular necrosis. After discontinuing steroids and reducing carboplatin, the patient continued with pembrolizumab, and their renal function returned to normal within two months. Discussion: Combining checkpoint inhibitors and platinum-based therapies may result in AKI. The standard method of examining kidney tissue may not provide sufficient information about the effects of these drugs on the kidneys. To address this issue, we recommend incorporating an assessment of the analysis of the expression of PDL1 and p53. This personalized approach will help identify the best treatment option for the patient while ensuring the best possible cancer treatment plan.

Comparative Analysis of Antithrombotic Therapy Outcomes in Mild Traumatic Brain-Injury Patients: A Focus on Bleeding Risk and Hospital-Stay Duration.

BACKGROUND: Traumatic brain injury (TBI) in the elderly is a noteworthy pathology due to the exponential increase in population age, and the effects of antiplatelet and anticoagulation on patients' outcomes are still a matter of dispute. The aim of the present study was to evaluate the impact of various antithrombotic agents on patients with mild TBI, focusing on the risk of intracranial bleeding (ICH) and length of hospitalization (LOS). METHODS: A retrospective analysis was conducted, including patients with a diagnosis of TBI admitted to the Emergency Department between 2021 and 2022. Patients were classified according to the concurrent antithrombotic therapy as aspirin (ASA), antiplatelets, direct oral anticoagulants (DOACs), and low-molecular-weight heparin (LMWH). The primary outcome was the ICH occurrence, while the secondary outcome was the LOS. The statistical analysis was performed via logistic regression models in R and STATA 13.1 software. Fisher's exact test was used for the statistical significance. RESULTS: 267 patients with mild TBI were included; 148 were not on antithrombotic agents, 43 were on aspirin, 33 on DOACs, 5 on LMWH, 22 on antiplatelets, and 16 on VKA. Out of the total, 9 patients experienced ICH, none of which were on DOACs, LMWH, or VKA, but 4-out of 65-were on antiplatelets, and 5-out of 148-were not on antithrombotic therapies. Patients not on antithrombotic therapy had the shortest LOS at 0.46 days, while those on VKA had the longest LOS at 1.19 days; similar trends were observed for patients on DOAC and LMWH. CONCLUSIONS: The results reveal that TBI patients on anticoagulants/antiplatelets had longer hospital stays compared with those on aspirin alone. Notably, VKA was the strongest predictor for an extended LOS. Regarding ICH, patients taking only aspirin were twice as likely to experience bleeding compared with those on anticoagulants/antiplatelets. However, to achieve statistically significant evidence, further research with a larger cohort of patients is needed.

Treatment strategies for ANCA-associated vasculitides: from standard protocols to future horizons.

INTRODUCTION: ANCA-associated vasculitides (AAV), classified into granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis represent a group of disorders characterized by necrotizing vasculitis of small vessels, endothelial injury and tissue damage. The outcomes and prognosis of AAV have undergone significant changes with the introduction of glucocorticoids (GCs) and other immunosuppressants (cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil). The enhanced understanding of pathogenesis has subsequently led to the incorporation into clinical practice of drugs targeting specific therapeutic targets. AREAS COVERED: After an extensive literature search of Pubmed, Medline, Embase of the most recent evidence, we provide an overview of available treatments, highlighting how newer drugs have integrated into standard protocols. Our review also explores potential new therapeutic targets, including B cell depletion and inhibition, T cell inhibition, complement inhibition, and IL-5 and IgE inhibition. EXPERT OPINION: There is hope that the new treatment targets currently under study in AAV may enable a faster and more lasting clinical response, ensuring the reduction of possible side effects from therapies. Moreover, numerous aspects necessitate further exploration in the future, such as tailoring of GCs, integration of GCs-sparing agents, efficacy of combination therapy, optimal maintenance therapy, to reduce organ-damage and improve quality of life.

Integrated protocol for the prevention and treatment of skin ulcers in patients with end-stage renal disease.

Chronic Kidney Disease (CKD) is an escalating global health concern, affecting more than 10 % of the general population worldwide, amounting to over 800 million individuals. One of its major complications for patients is the high prevalence of skin ulcers . This study aims to develop a protocol for ulcer management within the context of a hospital-based dialysis center. The success of this strategy is deeply rooted in the collaboration of a multidisciplinary team, continually enriched by specialist training. The clinical nurse specialist (CNS) in wound care plays a pivotal role in this approach. By employing a systematic methodology, the protocol is tailored to emphasize holistic care for patients diagnosed with end-stage renal disease undergoing hemodialysis. It accentuates the significance of proactive prevention, in-depth patient education, and the immediate identification of early wound signs. The research underscores the necessity to further weave in specialized training for ulcer care, ensuring each hospital visit is maximized for efficiency and effectiveness. Central to this protocol is the understanding that CKD is a growing concern, that the optimal management of ulcers relies heavily on multidisciplinary collaboration, and that an emphasis on prevention, patient education, and timely wound recognition is crucial to enhance patient care and experience.

C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis.

Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are types of membranoproliferative glomerulonephritis classified as C3 glomerulopathies. These conditions are characterized by an increased number of intraglomerular cells and diffuse thickening of the glomerular capillary walls, along with the deposition of C3 and minimal or absent immunoglobulin deposits. The underlying cause of both DDD and C3Gn is an abnormal activation of the alternative complement pathway, which can result from acquired or genetic alteration. In acquired forms of DDD and C3GN, the dysregulation of the alternative pathway is commonly induced by the presence of C3 nephritic factors (C3NeFs), which are autoantibodies that stabilize C3 convertase. Both DDD and C3GN can affect individuals of any age, but DDD is primarily diagnosed in children, whereas C3GN tends to be diagnosed at a significantly higher age. The presenting features of these diseases are variable and may include proteinuria, hematuria, hypertension, or kidney failure. A common finding in these diseases is low serum C3 levels with normal serum C4 levels. Chronic deterioration of renal function is commonly observed in DDD and C3GN, often leading to end-stage renal disease (ESRD), especially in DDD. Kidney transplantation outcomes in patients with these conditions are characterized by histological recurrence, which may contribute to higher rates of allograft failure.

Herpes zoster in lupus nephritis: experience on 292 patients followed up for 15 years.

Objectives: To evaluate the prevalence, incidence, and predictors of herpes zoster (HZ) development in lupus nephritis (LN). Methods: This retrospective study included 292 LN patients to determine HZ incidence during the last decades and its correlation with LN activity. LN patients with HZ were matched with LN patients without HZ in a 1:2 ratio based on sex, age, year of LN diagnosis, and LN histological class at kidney biopsy to assess HZ risk factors. Statistical tests included t-test, U-test, and Fisher's test. Univariate and multivariate logistic regression analyses were conducted to identify potential risk factors. Results: HZ occurred after LN diagnosis in 66 patients (prevalence 22.6%) with an average of 8.7 years (range 0.2-28.4 years). Although with the potential limitations of the retrospective nature and the extensive duration of the study, the incidence of HZ was 15.6/1,000 person-years, increasing from 6.9 before 1980 to 16.0 in the 1990s and 43.9 after 2010. HZ onset was unrelated to LN activity. LN was active in 43% of cases and quiescent in the other 57% of cases at HZ diagnosis. The percentage of patients who developed lupus flares during the year after HZ (18.9%) was not different from that which occurred during the year before HZ (17.2%, p = 0.804). After excluding confounding factors through matching, the univariate analysis suggested that cyclosporin during induction therapy (p = 0.011) and higher cumulative doses of glucocorticoids (GCs; >50 g, p = 0.004), cyclophosphamide (CYC; >5 g, p = 0.001), and mycophenolate mofetil (MMF > 1,000 g, p = 0.007) predisposed patients to HZ. Univariate and multivariate analyses revealed a protective role of azathioprine (p = 0.008) and methylprednisolone pulses (p = 0.010) during induction therapy. Conclusions: HZ occurs unpredictably throughout the course of LN, underscoring the importance of continuous monitoring for these patients. In addition, the incidence of HZ seems to have increased in recent decades. Induction therapy with azathioprine and methylprednisolone pulses appears to provide protection, while higher cumulative doses of GCs, CYC, and MMF increase susceptibility.

Using Renal Elastography to Predict the Therapeutic Response of Nephrological Patients.

BACKGROUND: The standard method for assessing chronic renal damage is renal biopsy, which has limitations due to its invasiveness. Ultrasound elastography is a non-invasive technique that quantifies tissue elasticity and can be used to determine Young's modulus (YM). Although this breakthrough technology has been successfully employed to evaluate liver stiffness and the extent of fibrosis, its application in kidney-related conditions still needs improvement. METHODS: Our study aimed to verify the correlation between renal elastography and the chronic histological score determined via renal biopsy, evaluate the correlation between elastography and response to treatment in the short-term follow-up (6 months), and compare elastography data between renal disease patients (AKD-P) and healthy controls (HP). RESULTS: The analyzed population consisted of 82 patients (41 HP and 41 AKD-P). The AKD-P were divided into responders (R) or non-responders (NR) based on the criteria established by the guidelines. No association was found between renal stiffness and chronic histological score. Elastography data revealed median YM values of 6.15 kPa for AKD-P and 12.2 kPa for HP, with a statistically significant difference. The median YM values of the R and NR groups were 7.4 KPa and 5.6 KPa, respectively (p = 0.037). CONCLUSIONS: Patient responsiveness was associated with YM, with lower values observed in the NR group. We also found that the healthy controls exhibited significantly higher YM values than the renal disease population.

Comparison of EULAR/PRINTO/PReS Ankara 2008 and 2022 ACR/EULAR Classification Criteria for Granulomatosis with Polyangiitis in Children.

OBJECTIVE: Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody-associated vasculitis. The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR)-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in pediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA. METHODS: Retrospective data of pediatric patients with GPA in 20 centers from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated. RESULTS: The study included 77 patients with GPA and 108 controls (immunoglobulin A vasculitis (n = 44), Takayasu's arteritis (n = 20), microscopic polyangiitis (n = 16), polyarteritis nodosa (n = 14), Behçet's disease (n = 12), eosinophilic granulomatosis with polyangiitis (n = 1), and Cogan's syndrome (n = 1)) with a median age of 17.8 and 15.2 years, respectively. Of patients with GPA, constitutional symptoms (85.7%) and ear-nose-throat involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (p= 0.229 and p= 0.733, respectively). CONCLUSION: In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.

Hospital Malnutrition in the Medicine and Neurology Departments: A Complex Challenge.

Hospital malnutrition is especially common among elderly patients with neurological deficits or dementia. These conditions can be exacerbated by unpalatable diets and issues such as dysphagia and presbyphagia. Our study aimed to investigate the prevalence of malnutrition in patients on a homogenized diet and to identify potential correlations with specific clinical variables. We conducted a retrospective observational study in compliance with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines. The study encompassed 82 patients, mainly elderly and diagnosed with neurodegenerative diseases. Upon initial assessment, 46.34% of the sample displayed a risk of malnutrition based on the Malnutrition Universal Screening Tool (MUST), and 62.20% were classified as malnourished based on the Global Leadership Initiative on Malnutrition (GLIM) criteria. Only 45.12% retained autonomy in food intake. Weight loss identified prior to the study was closely tied to malnutrition and influenced BMI. Moreover, autonomy in food intake was strongly associated with a prolonged hospital stay (LOS), and a similar trend was observed for water intake. Our findings emphasize the importance of promptly recognizing patients at risk of malnutrition, especially within such a vulnerable population. Autonomy in food intake and hydration emerge as critical indicators in the clinical management of hospitalized patients.

Changing Phenotypes and Clinical Outcomes Over Time in Microscopic Polyangiitis.

Introduction: Diagnosis and management of microscopic polyangiitis (MPA) have evolved considerably over the past decades, but it is unknown whether clinical and histological presentation and patient and renal outcomes have changed accordingly. Methods: We compared clinical and histopathological characteristic at diagnosis, risk of death, end-stage kidney disease (ESKD), and relapse rate in patients diagnosed with MPA between 1980 and 2022, after grouping them in 2 periods (p): p1980-2001 and p2002-2022. We compared the mortality rate between the 2 periods using Kaplan-Meier estimator and Cox-regression, and competing risks of ESKD and death using the Aalen-Johansen estimator, Fine-Gray multiple regression, and multistate models. Results: Out of 187 patients, 77 were in p1980-2001 and 110 in p2002 to 2022. Patients in p2002 to 2022 were older (66.2 ± 14.0 SD vs. 57.7 ± 15.8; P < 0.001), had a better kidney function (estimated glomerular filtration rate [eGFR] 25.9 ± 24.8 vs. 21.5 ± 28.2 ml/min per 1.73 m2; P = 0.011) and a lower prevalence of the Berden sclerotic class (5.9 vs. 20.9%; P = 0.011). Despite a similar crude and adjusted patient survival, the risk of ESKD decreased during p2002 to 2022 (subdistribution hazard ratio [HR] 0.30, 95% confidence interval [CI]: 0.16-0.57; P < 0.001). The results remained significant after accounting for death after ESKD and after adjusting for potential confounders (HR 0.33 [95% CI: 0.18-0.63; P < 0.001]). The risk of relapse was numerically higher during p2002 to 2022 (subdistribution-HR 1.64 [95% CI: 0.95-2.83; P = 0.075]). Conclusion: MPA kidney involvement has become less severe over the past decades, leading to a reduced risk of ESKD and a higher relapse rate, despite a comparable risk of death.

Renal involvement in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing vasculitis, which typically affects small-to medium-sized blood vessels. It is characterized by the presence of tissue infiltrates rich in eosinophils, along with the formation of granulomatous lesions. About 40% of cases have positive anti-neutrophil cytoplasm antibodies (ANCA), with predominant perinuclear staining, and anti-myeloperoxidase (anti-MPO) specificity in about 65% of cases. Typical manifestations of EGPA include the late onset of asthma, nasal and sinus-related symptoms, peripheral neuropathy, and significant eosinophilia observed in the peripheral blood. In contrast to granulomatosis with polyangiitis and microscopic polyangiitis, renal involvement in EGPA is less frequent (about 25%) and poorly studied. Necrotizing pauci-immune crescentic glomerulonephritis is the most common renal presentation in patients with ANCA-positive EGPA. Although rarely, other forms of renal involvement may also be observed, such as eosinophilic interstitial nephritis, mesangial glomerulonephritis, membranous nephropathy, or focal sclerosis. A standardized treatment for EGPA with renal involvement has not been defined, however the survival and the renal outcomes are usually better than in the other ANCA-associated vasculitides. Nonetheless, kidney disease is an adverse prognostic factor for EGPA patients. Larger studies are required to better describe the renal involvement, in particular for patterns different from crescentic glomerulonephritis, and to favor the development of a consensual therapeutic approach. In this article, in addition to personal data, we will review recent findings on patient clinical phenotypes based on ANCA, genetics and the impact of biological drugs on disease management.

Microplastics and Kidneys: An Update on the Evidence for Deposition of Plastic Microparticles in Human Organs, Tissues and Fluids and Renal Toxicity Concern.

Plastic pollution became a main challenge for human beings as demonstrated by the increasing dispersion of plastic waste into the environment. Microplastics (MPs) have become ubiquitous and humans are exposed daily to inhalation or ingestion of plastic microparticles. Recent studies performed using mainly spectroscopy or spectrometry-based techniques have shown astounding evidence for the presence of MPs in human tissues, organs and fluids. The placenta, meconium, breast milk, lung, intestine, liver, heart and cardiovascular system, blood, urine and cerebrovascular liquid are afflicted by MPs' presence and deposition. On the whole, obtained data underline a great heterogeneity among different tissue and organs of the polymers characterized and the microparticles' dimension, even if most of them seem to be below 50-100 µm. Evidence for the possible contribution of MPs in human diseases is still limited and this field of study in medicine is in an initial state. However, increasing studies on their toxicity in vitro and in vivo suggest worrying effects on human cells mainly mediated by oxidative stress, inflammation and fibrosis. Nephrological studies are insufficient and evidence for the presence of MPs in human kidneys is still lacking, but the little evidence present in the literature has demonstrated histological and functional alteration of kidneys in animal models and cytotoxicity through apoptosis, autophagy, oxidative stress and inflammation in kidney cells. Overall, the manuscript we report in this review recommends urgent further study to analyze potential correlations between kidney disease and MPs' exposure in human.

Ursodeoxycholic Acid Does Not Improve COVID-19 Outcome in Hospitalized Patients.

Ursodeoxycholic acid (UDCA) was demonstrated to reduce susceptibility to SARS-CoV-2 infection in vitro and improve infection course in chronic liver diseases. However, real-life evidence is lacking. We analyzed the impact of UDCA on COVID-19 outcomes in patients hospitalized in a tertiary center. Between January 2020 and January 2023, among 3847 patients consecutively hospitalized for COVID19, 57 (=UDCA group) were taking UDCA. The UDCA and the control groups (n = 3790) did not differ concerning comorbidities including diabetes mellitus type 2 (15.8% vs. 12.8%) and neoplasia (12.3% vs. 9.4%). Liver diseases and vaccination rate were more common in the UDCA group (14.0% vs. 2.5% and 54.4% vs. 30.2%, respectively). Overall mortality and CPAP treatment were 22.8 % and 15.7% in the UDCA, and 21.3% and 25.9% in the control group. Mortality was similar (p = 0.243), whereas UDCA was associated with a lower rate of CPAP treatment (OR = 0.76, p < 0.05). Treatment with UDCA was not an independent predictor of survival in patients hospitalized for COVID-19.

Is per-protocol kidney biopsy required in lupus nephritis?

Baseline kidney biopsy is recommended in lupus nephritis (LN). Biopsy allows to classify different forms of LN and differentiate other forms of renal involvement, such as tubulo-interstitial nephritis or thrombotic microangiopathy. The indications for repeat biopsy are more controversial. Some authors feel that good clinical monitoring is sufficient to assess prognosis and make therapeutic decisions. Based on the recently demonstrated discordance between clinical and histological response, some physicians recommend per-protocol biopsies either at 6 months in stable patients to verify the response to induction therapy, or after one-to-two years to assess treatment efficacy and tune the duration of maintenance therapy. Others recommend repeating kidney biopsy in case of incomplete response or to discriminate between active and chronic lesions. By definition, a per-protocol kidney biopsy differs from a repeat biopsy in that the former is foreseen at fixed timepoints, regardless of the clinical response. Although any decision should always consider the patient's overall clinical condition, there are no doubts that repeat kidney biopsy represents a useful tool in difficult cases to evaluate treatment response, modulate treatment intensity, and predict long-term renal outcome both in quiescent lupus and during flares. How to harmonize per-protocol biopsies in the LN course remains challenging.

Prevalence and clinical significance of ANCA positivity in lupus nephritis: a case series of 116 patients and literature review.

The prevalence and clinical significance of anti-neutrophil cytoplasmic antibodies [ANCAs] in patients with lupus nephritis [LN] is not fully elucidated. Our aim was to determine whether LN patients with ANCA positivity had different clinicopathological features and outcomes compared to ANCA-negative patients. METHODS: Among our LN patients we retrospectively selected those who underwent ANCA testing the day of the kidney biopsy and before the start of induction treatment. Clinical/histopathological features at kidney biopsy and renal outcome of ANCA-positive patients were compared with those of ANCA-negative subjects. RESULTS: We included 116 Caucasian LN patients in the study; 16 patients [13.8%] were ANCA-positive. At kidney biopsy, ANCA-positive patients presented more frequently with an acute nephritic syndrome than ANCA-negative ones; the difference however does not reach statistical significance [44 vs. 25%, p = 0.13]. At histological evaluation, proliferative classes [100% vs 73%; p = 0.02], class IV [68.8% vs 33%; p < 0.01] and necrotizing tuft lesions [27 vs 7%, p = 0.04] were more frequent, and the activity index was higher [10 vs 7; p = 0.03] in ANCA-positive than in ANCA-negative patients. Despite worse histological features, after a 10-year observation period, there were no significant differences in the number of patients with chronic kidney function impairment (defined as eGFR < 60 mL/min per 1.73 m2) between the ANCA-positive and negative groups [24.2 vs 26.6%, p = 0.9]. This could be the result of the more aggressive therapy, with rituximab plus cyclophosphamide, that ANCA-positive patients received more frequently than ANCA-negative ones [25 vs. 1.3%, p < 0.01]. CONCLUSIONS: ANCA-positive LN patients frequently have histological markers of severe activity (proliferative classes and high activity index) that require timely diagnosis and aggressive therapy to limit the development of irreversible chronic kidney damage.

Goodpasture syndrome and anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (anti-GBM) disease is a rare life-threatening small vessel vasculitis that typically affects the capillaries of kidneys and lungs, with most of patients developing rapidly progressive crescentic glomerulonephritis, and 40%-60% concomitant alveolar haemorrhage. It is caused by the deposition in alveolar and glomerular basement membrane of circulating autoantibodies directed against antigens intrinsic to the basement membrane. The exact mechanism that induces the formation of autoantibodies is unknown, but probably environmental factors, infections or direct damage to kidneys and lungs may trigger the autoimmune response in genetically susceptible individuals. Initial therapy includes corticosteroids and cyclophosphamide to prevent autoantibodies production, and plasmapheresis to remove the circulating autoantibodies. Good renal outcomes may be achieved by a prompt treatment initiation. However, when patients present with severe renal failure requiring dialysis or with a high proportion of glomerular crescents at biopsy, renal outcomes are bad. Relapses are rare and when renal involvement is present, the suspect of concomitant diseases, such as ANCA-associated vasculitis and membranous nephropathy, should be raised. Imlifidase is showing promising results, which if confirmed will cause a paradigm shift in the treatment of this disease.

Kidney Biopsy in Pregnant Women with Glomerular Diseases: Focus on Lupus Nephritis.

Despite significant improvements of renal and obstetrical management, pregnancies in women with glomerular diseases and with lupus nephritis continue to be associated with increased complications both for the mother and the fetus as compared to those of pregnancies in healthy women. To reduce the risk of these complications, planning pregnancy in a phase of stable remission of the underlining disease is necessary. A kidney biopsy is an important event in any phase of pregnancy. A kidney biopsy can be of help during counselling before pregnancy in cases of incomplete remission of the renal manifestations. In these situations, histological data may differentiate active lesions that require the reinforcement of therapy from chronic irreversible lesions that may increase the risk of complications. In pregnant women, a kidney biopsy can identify new-onset systemic lupus erythematous (SLE) and necrotizing or primitive glomerular diseases and distinguish them from other, more common complications. Increasing proteinuria, hypertension, and the deterioration of kidney function during pregnancy may be either due to a reactivation of the underlying disease or to pre-eclampsia. The results of the kidney biopsy suggest the need to initiate an appropriate treatment, allowing the progression of the pregnancy and the fetal viability or the anticipation of delivery. Data from the literature suggest avoiding a kidney biopsy beyond 28 weeks of gestation to minimize the risks associated with the procedure vs. the risk of preterm delivery. In case of the persistence of renal manifestations after delivery in women with a diagnosis of pre-eclampsia, a renal kidney assessment allows the final diagnosis and guides the therapy.

Kinetics of the Cell Cycle Arrest Biomarkers (TIMP2 and IGFBP7) for the Diagnosis of Acute Kidney Injury in Critically Ill COVID-19 Patients.

BACKGROUND: Acute kidney injury (AKI) is highly prevalent in critical COVID-19 patients. The diagnosis and staging of AKI are based on serum creatinine (sCr) and urinary output criteria, with limitations in the functional markers. New cell-cycle arrest biomarkers [TIMP2]*[IGFBP7] have been proposed for early detection of AKI, but their role in critically ill COVID-19 patients is poorly understood. METHODS: We conducted an observational study to assess the performance of [TIMP2]*[IGFBP7] for the detection of AKI in critical COVID-19 patients admitted to our intensive care unit (ICU). We sampled urinary [TIMP2]*[IGFBP7] levels at ICU admission, 12 h, 24 h, and 48 h, and compared the results to the development of AKI, as well as baseline and laboratory data. RESULTS: Forty-one patients were enrolled. The median age was 66 years [57-72] and most were males (85%). Thirteen patients (31.7%) developed no/mild stage AKI, 19 patients (46.3%) moderate AKI, and nine patients (22.0%) severe AKI. The ICU mortality was 29.3%. sCr levels in the Emergency Department or at ICU admission were not significantly different according to AKI stage. [TIMP-2]*[IGFBP-7] urinary levels were elevated in severe AKI at 12 h after ICU admission, but not at ICU admission or 24 h or 48 h after ICU admission. CONCLUSION: Urinary biomarkers [TIMP-2]*[IGFBP-7] were generally increased in this population with a high prevalence of AKI, and were higher in patients with severe AKI measured at 12 h from ICU admission. Further studies are needed to evaluate the best timing of these biomarkers in this population.

Renal sarcoidosis.

Sarcoidosis is a systemic inflammatory disease of unknown etiology. The pathogenesis rests on an aberrant T cell response to unidentified antigens in individuals predisposed by genetic and environmental factors. Increased expression of polarized macrophages and disequilibrium between effector and regulator T cells contribute to the formation of noncaseating granulomas, that are frequently found in affected organs. The main kidney abnormalities in sarcoidosis are granulomatous interstitial nephritis (GIN) and hypercalcemia-related disorders. The clinical diagnosis is difficult. The outcome is variable, ranging from spontaneous remission to end-stage kidney disease (ESKD). Early diagnosis and prompt treatment with corticosteroids can improve the prognosis. Hypercalcemia may be responsible for acute kidney injury (AKI) caused by vasoconstriction of afferent arterioles. Complications of persistent hypercalcemia include nephrocalcinosis and renal stones. In patients with ESKD, dialysis and transplantation can offer results comparable to those observed in patients with other causes of kidney failure. Based on a review of the literature, we present an overview of the etiopathogenesis, the renal manifestations of sarcoidosis and their complications, management and prognosis.