Anti-phospholipase A2 receptor antibody and spontaneous remission in membranous nephropathy

Anti-phospholipase A2 receptor antibody; Membranous nephropathy; Spontaneous remissionAnticòs del receptor anti-fosfolipasa A2; Nefropatia membranosa; Remissió espontàniaAnticuerpo del receptor anti-fosfolipasa A2; Nefropatía membranosa; Remisión espontáneaMembranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in native kidney biopsies from adults. In 2009, antibodies to the M-type receptor of phospholipase A2 (anti-PLA2R) were identified in idiopathic MN patients, both within the kidney and in the circulation. The clinical course of idiopathic MN is variable and ranges from spontaneous remission to end-stage renal disease. Clinical variables such as proteinuria levels, patient sex, age and renal function at diagnosis have been associated with renal MN progression. In this editorial, we update the importance of anti-PLA2R levels as a prognostic marker in idiopathic MN at the diagnosis of the diseas

The New Era for Reno-Cardiovascular Treatment in Type 2 Diabetes

Diabetes; Diabetic kidney disease; Dipeptidyl peptidase 4 inhibitorsDiabetis; Nefropatia diabètica; Inhibidors de la dipeptidil peptidasa 4Diabetes; Nefropatía diabética; Inhibidores de la dipeptidil peptidasa 4Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease in the developed world. Until 2016, the only treatment that was clearly demonstrated to delay the DKD was the renin-angiotensin system blockade, either by angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. However, this strategy only partially covered the DKD progression. Thus, new strategies for reno-cardiovascular protection in type 2 diabetic patients are urgently needed. In the last few years, hypoglycaemic drugs, such as sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, demonstrated a cardioprotective effect, mainly in terms of decreasing hospitalization for heart failure and cardiovascular death in type 2 diabetic patients. In addition, these drugs also demonstrated a clear renoprotective effect by delaying DKD progression and decreasing albuminuria. Another hypoglycaemic drug class, dipeptidyl peptidase 4 inhibitors, has been approved for its use in patients with advanced chronic kidney disease, avoiding, in part, the need for insulinization in this group of DKD patients. Studies in diabetic and non-diabetic experimental models suggest that these drugs may exert their reno-cardiovascular protective effect by glucose and non-glucose dependent mechanisms. This review focuses on newly demonstrated strategies that have shown reno-cardiovascular benefits in type 2 diabetes and that may change diabetes management algorithms.The authors are current recipients of research grants from the FONDO DE INVESTIGACIÓN SANITARIA-FEDER, ISCIII, PI17/00257, and REDINREN, RD16/0009/0030

How to Assess Diabetic Kidney Disease Progression? From Albuminuria to GFR

Malaltia renal crònica; Diabetis mellitus; Malaltia renal diabèticaEnfermedad renal crónica; Diabetes mellitus; Enfermedad renal diabéticaChronic kidney disease; Diabetes mellitus; Diabetic kidney diseaseDiabetic kidney disease (DKD) is one of the most relevant complications of type 2 diabetes and dramatically increases the cardiovascular risk in these patients. Currently, DKD is severely infra-diagnosed, or its diagnosis is usually made at advanced stages of the disease. During the last decade, new drugs have demonstrated a beneficial effect in terms of cardiovascular and renal protection in type 2 diabetes, supporting the crucial role of an early DKD diagnosis to permit the use of new available therapeutic strategies. Moreover, cardiovascular and renal outcome trials, developed to study these new drugs, are based on diverse cardiovascular and renal simple and composite endpoints, which makes difficult their interpretation and the comparison between them. In this article, DKD diagnosis is reviewed, focusing on albuminuria and the recommendations for glomerular filtration rate measurement. Furthermore, cardiovascular and renal endpoints used in classical and recent cardiovascular outcome trials are assessed in a pragmatic way.The authors are current recipients of research grants from the Fondo de Investigación Sanitaria-Feder—Instituto de Salud Carlos III (PI17/00257) and REDinREN (RD16/0009/0030)

A hierarchical AI-based control plane solution for multitechnology deterministic networks

Following the Industry 4.0 vision of a full digitiSation of the industry, time-critical services and applications, allowing network infrastructures to deliver information with determinism and reliability, are becoming more and more relevant for a set of vertical sectors. As a consequence, deterministic network solutions are progressively emerging, albeit they are still bounded to specific technological domains. Even considering the existence of interconnected deterministic networks, the provision of an end-to-end (E2E) deterministic service over them must rely on a specific control plane architecture, capable of seamlessly integrate and control the underlying multi-technology data plane. In this work, we envision such a control plane solution, extending previous works and exploiting several innovations and novel architectural concepts. The proposed control architecture is service-centric, in order to provide the necessary flexibility, scalability, and modularity to deal with a heterogenous data plane. The architecture is hierarchical and encompasses a set of management platforms to interact with specific network technologies overarched by an E2E platform for the management, monitoring, and control of E2E deterministic services. Furthermore, Artificial Intelligence (AI) and Digital Twinning are used to enable network predictability and automation, as well as smart resource allocation, to ensure service reliability in dynamic scenarios where existing services may terminate and new ones may need to be deployed

Acute interstitial nephritis associated with immune checkpoint inhibitors: a single-centre experience

Nefritis intersticial aguda; Inhibidors de punts de control; Biòpsia de ronyóNefritis intersticial aguda; Inhibidores de puntos de control; Biopsia renalAcute interstitial nephritis; Checkpoint inhibitors; Kidney biopsyBackground Checkpoint inhibitors (CPIs) are used to treat solid organ metastatic malignancies. They act by triggering a vigorous immune response against tumoural cells, preventing their proliferation and metastasis. However, this is not a selective response and can cause immune-related adverse events (irAEs). The kidney can potentially be damaged, with an incidence of irAEs of 1–4%. The most frequent type of toxicity described is acute interstitial nephritis (AIN). Methods We conducted a study of patients with solid organ metastatic malignancies treated with immunotherapy who developed acute renal injury and underwent kidney biopsy in the last 14 months at the Vall d’Hebron University Hospital. Results In all, 826 solid organ malignancies were treated with immunotherapy in our centre, 125 of them (15.1%) developed acute kidney injury (AKI), 23 (18.4% of AKI) visited the nephrology department and 8 underwent kidney biopsy. The most frequent malignancy was lung cancer, in five patients (62%), followed by two patients (25%) with melanoma and one patient (12%) with pancreatic cancer. Four patients (50%) had already received previous oncological therapy, and for the remaining four patients (50%), CPI was the first-line therapy. Five patients (62%) were treated with anti-programmed cell death protein 1, three patients (37%) received anti-programmed death ligand 1 and two (25%) patients were treated in combination with anti-cytotoxic T-lymphocyte antigen 4. The time between the start of CPI and the onset of the AKI ranged from 2 to 11 months. The most frequent urine findings were subnephrotic-range proteinuria, with a mean protein:creatinine ratio of 544 mg/g (standard deviation 147) and eosinophiluria. All patients were biopsied after being diagnosed with AIN. Three patients (37%) received treatment with pulses of methylprednisolone 250–500 mg/day and five patients (62%) received prednisone 1 mg/kg/day. Seven patients (87%) experienced recovery of kidney function and one patient (12%) progressed to chronic kidney disease. Conclusions We report on eight patients with CPI-related AIN diagnosed in the last 14 months at our centre. The novel immunotherapy treatment of metastatic solid organ malignancies carries a higher risk of irAEs. The kidney is one of the most commonly affected organs, frequently presenting as an AIN and exhibiting a favourable response to steroid treatment.The authors are current recipients of research grants from the Fondo de Investigación Sanitaria-Feder, ISCIII (PI17/00257) and Redinren (RD16/0009/0030). M.B. performed this work as the basis of her thesis at the Department de Medicina of Universitat Autònoma de Barcelona

Challenges in primary focal segmental glomerulosclerosis diagnosis: from the diagnostic algorithm to novel biomarkers

Biomarcadors; Algoritme de diagnosi; Glomerulosclerosi segmentària focalBiomarcadores; Algoritmo de diagnóstico; Glomeruloesclerosis segmentaria focalBiomarkers; Diagnosis algorithm; Focal segmental glomerulosclerosisPrimary or idiopathic focal segmental glomerulosclerosis (FSGS) is a kidney entity that involves the podocytes, leading to heavy proteinuria and in many cases progresses to end-stage renal disease. Idiopathic FSGS has a bad prognosis, as it involves young individuals who, in a considerably high proportion (∼15%), are resistant to corticosteroids and other immunosuppressive treatments as well. Moreover, the disease recurs in 30–50% of patients after kidney transplantation, leading to graft function impairment. It is suspected that this relapsing disease is caused by a circulating factor(s) that would permeabilize the glomerular filtration barrier. However, the exact pathologic mechanism is an unsettled issue. Besides its poor outcome, a major concern of primary FSGS is the complexity to confirm the diagnosis, as it can be confused with other variants or secondary forms of FSGS and also with other glomerular diseases, such as minimal change disease. New efforts to optimize the diagnostic approach are arising to improve knowledge in well-defined primary FSGS cohorts of patients. Follow-up of properly classified primary FSGS patients will allow risk stratification for predicting the response to different treatments. In this review we will focus on the diagnostic algorithm used in idiopathic FSGS both in native kidneys and in disease recurrence after kidney transplantation. We will emphasize those potential confusing factors as well as their detection and prevention. In addition, we will also provide an overview of ongoing studies that recruit large cohorts of glomerulopathy patients (Nephrotic Syndrome Study Network and Cure Glomerulonephropathy, among others) and the experimental studies performed to find novel reliable biomarkers to detect primary FSGS.The authors are current recipients of research grants from the Fondo de Investigación Sanitaria-Feder, Instituto de Salud Carlos III (PI17/00257, PI18/01704 and PI18/01832) and REDinREN (RD16/0009/0030)

Safety of Obtaining an Extra Biobank Kidney Biopsy Core

Biobank; Chronic kidney disease; Kidney biopsyBiobanco; Enfermedad renal cronica; Biopsia renalBiobanc; Malaltia renal crònica; Biòpsia de ronyóBackground and objectives: Kidney biopsy (KB) is the “gold standard” for the diagnosis of nephropathies and it is a diagnostic tool that presents a low rate of complications. Nowadays, biobank collections of renal tissue of patients with proven renal pathology are essential for research in nephrology. To provide enough tissue for the biobank collection, it is usually needed to obtain an extra kidney core at the time of kidney biopsy. The objective of our study is to evaluate the complications after KB and to analyze whether obtaining an extra core increases the risk of complications. Material and methods: Prospective observational study of KBs performed at Vall d’Hebron Hospital between 2019 and 2020. All patients who accepted to participate to our research biobank of native kidney biopsies were included to the study. Clinical and laboratory data were reviewed and we studied risk factors associated with complications. Results: A total of 221 patients were included, mean age 56.6 (±16.8) years, 130 (58.8%) were men, creatinine was 2.24 (±1.94) mg/dL, proteinuria 1.56 (0.506–3.590) g/24 h, hemoglobin 12.03 (±2.3) g/dL, INR 0.99 (±0.1), and prothrombin time (PT) 11.86 (±1.2) s. A total of 38 patients (17.2%) presented complications associated with the procedure: 13.1% were minor complications, 11.3% (n = 25) required blood transfusion, 1.4% (n = 3) had severe hematomas, 2.3% (n = 5) required embolization, and 0.5% (n = 1) presented arterio-venous fistula. An increased risk for complication was independently associated with obtaining a single kidney core (vs. 2 and 3 cores) (p = 0.021). Conclusions: KB is an invasive and safe procedure with a low percentage of complications. Obtaining an extra kidney core for research does not increase the risk of complications during the intervention, which remains low in concordance with previously published reports.The authors are current recipients of research grant from Red de Investigación Renal (REDINREN, RD16/0009/0030). (RICORS, RD21/0005/0016)

COVID-19 infection and renal injury: where is the place for acute interstitial nephritis disease?

COVID-19; Nefritis tubulointersticial aguda; Biòpsia de ronyóCOVID-19; Nefritis tubulointersticial aguda; Biopsia de riñónCOVID-19; Acute tubulointerstitial nephritis; Kidney biopsyNovel coronavirus disease infection (coronavirus disease 2019, COVID-19) was declared a global pandemic in March 2020 and since then has become a major public health problem. The prevalence of COVID-19 infection and acute kidney injury (AKI) is variable depending on several factors such as race/ethnicity and severity of illness. The pathophysiology of renal involvement in COVID-19 infection is not entirely clear, but it could be in part explained by the viral tropism in the kidney parenchyma. AKI in COVID-19 infection can be either by direct invasion of the virus or as a consequence of immunologic response. Diverse studies have focused on the effect of COVID-19 on glomerulonephritis (GN) patients or the ‘novo’ GN; however, the effect of COVID-19 in acute tubulointerstitial nephritis (ATIN) has been scarcely studied. In this article, we present five cases with different spectrums of COVID-19 infection and ATIN that may suggest that recent diagnosis of ATIN is accompanied by a worse clinical prognosis in comparison with long-term diagnosed ATIN.This research was funded by ISCIIII-FEDER and ISCIII-RETICS REDinREN, grant number PI17/00257, PI21/01292, RD16/0009/0030, and RICORS RD21/0005/0016. Enfermedad Glomerular Compleja del Sistema Nacional de Salud (CSUR), enfermedades glomerulares complejas

Focal and segmental glomerulosclerosis associated with COVID-19 infection

Glomeruloesclerosi; COVID-19Glomerulosclerosis; COVID-19Glomeruloesclerosis; COVID-1

The Presence of ANCA in IgA Crescentic Nephropathy Does Not Lead to Worse Prognosis with Intensive Rescue Treatment

Nefropatía por IgA; Autoanticuerpos anticitoplasma de neutrófilosIgA nephropathy; Antineutrophil cytoplasmic autoantibodiesNefropatia per IgA; Anticossos anticitoplasma de neutròfilsBackground: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. The concomitant presence of both crescentic proliferation and anti-neutrophil cytoplasmic autoantibodies (ANCA) in this pathology represents a rare coincidence. However, it is not clear to what extent the presence of ANCA (IgA or IgG) in these patients could have any clinical significance. The aim of the current work is to describe the presence of ANCA (IgA or IgG) in patients with IgAN and crescentic proliferation and its possible clinical implications. Methods: We retrospectively recruited all patients in our center with a histological diagnosis of IgAN with crescentic proliferation between January 2013 and December 2020. The main demographic and clinicopathologic data, fundamental histological characteristics, as well as the treatments implemented and main kidney outcomes, were collected and analyzed at a 6 and 12-month follow-up. Results: Between January 2013 and December 2020, a total of 17 adults were diagnosed with concomitant crescentic proliferation through a kidney biopsy of IgAN. Five (29.4%) patients showed ANCA, three (60%) showed IgA-ANCA and two (40%) showed IgG-ANCA. All ANCA-positive patients had some degree of crescentic proliferation. At diagnosis, the mean age of patients was 48 years old (range: 27–75). Nine of them were women (52%) and the most common clinical presentation was hypertension (71%). At the time of biopsy, the mean serum creatinine and proteinuria were 2.2 mg/dL (DS 1.42) and 3.5 g/mgCr (DS 1.22), respectively, with no statistical differences between ANCA-positive and -negative patients. Histological analyses showed that 11 out of the 12 (91%) ANCA-negative IgAN patients displayed less than 25% cellular crescents, whereas 100% of ANCA-positive IgAN patients displayed more than 25% cellular crescents (p = 0.04). Notably, five (30%) patients displayed fibrinoid necrosis, with four of them (80%) being IgAN-ANCA-positive (p = 0.01). Only one ANCA-negative patient needed renal replacement therapy (RRT) upon admission (5%). The mean serum creatinine and proteinuria were 1.94 mg/dL (DS 1.71) and 1.45 g/gCr (DS 1.78), respectively, within 6 months of immunosuppressive therapy. At 12-month follow-up, the mean creatinine was 1.57 mg/dL (DS 1). Four (23.5%) patients needed RRT at the end of the follow-up and four (23.5%) patients died. Conclusions: Probably due to the limited number of IgAN-ANCA-positive and IgAN-ANCA-negative patients, no significant differences were found between the clinical and laboratory characteristics. IgAN-ANCA-negative patients seemed to display less extracapillary proliferation than IgAN-ANCA-positive patients, who tended to show significantly higher fibrinoid necrosis. There were no differences regarding renal prognosis and patient survival after aggressive immunosuppressive therapy within 6 and 12 months when comparing the two samples