Transjugular Kidney Biopsy as a Safe Method to Increase the Etiological Diagnosis in Kidney Disease

Biopsia renal transyugular; Diagnóstico etiológico; Enfermedad renalBiòpsia renal transjugular; Diagnòstic etiològic; Malaltia renalTransjugular Kidney Biopsy; Etiological Diagnosis; Kidney Diseas

Immunotherapy and the Spectrum of Kidney Disease: Should We Individualize the Treatment?

Chronic kidney disease; Dialysis; ImmunotherapyEnfermedad renal cronica; Diálisis; InmunoterapiaMalaltia renal crònica; Diàlisi; ImmunoteràpiaThe new targeted cancer therapies including immune checkpoint inhibitors (ICIs) have been demonstrated to improve the survival of oncological patients, even in cases of metastatic cancer. In the past 5 years, several studies have revealed that ICI can produce several immune-mediated toxicities involving different organs, such as the skin, the gastrointestinal tract, the liver, and, of course, the kidney. The most frequent lesion of immunotoxicity in the kidney is acute interstitial nephritis (AIN), although other nephropathies have also been described as a consequence of the use of ICI, such as glomerulonephritis and acute thrombotic microangiopathy, among others. In addition, kidney rejection has also been reported in kidney transplant patients treated with ICI. Normally randomized clinical trials with ICI exclude patients with end-stage kidney disease, namely, patients undergoing dialysis and kidney transplant patients. Several important questions need to be addressed in relation to immunotherapy and patients with kidney disease: (a) when to start corticosteroid therapy in a patient with suspected acute kidney injury (AKI) related to ICI, (b) the moment of nephrologist referral and kidney biopsy indication, (c) management of ICI in patients undergoing dialysis, and (d) the effect of ICI in kidney transplantation, immunosuppressive personalized treatment, and risk of allograft rejection in kidney transplant patients. The objective of this review was to summarize the recently published literature on a wide spectrum of kidney disease patients with cancer and ICI. This review will address three main important groups of individuals with kidney disease and cancer immunotherapy, AKI associated with ICI, patients undergoing dialysis, and kidney transplant recipients. We believe that the information provided in this review will enlighten the personalized ICI treatment in individuals with a broader spectrum of kidney diseases.This research was funded by ISCIIII-FEDER and ISCIII-RETICS REDinREN, Grant Numbers PI17/00257, PI21/01292, RD16/0009/0030, and RICORS RD21/0005/0016. Enfermedad Glomerular Compleja del Sistema Nacional de Salud (CSUR), enfermedades glomerulares complejas

Kidney Biopsy in Patients with Cancer along the Last Decade: A Multicenter Study

Kidney biopsy; Renal pathology; Solid organ neoplasmBiòpsia renal; Patologia renal; Neoplàsia d'òrgans sòlidsBiopsia renal; Patología renal; Neoplasia de órganos sólidosBackground: Currently, following the new advances in cancer treatments and the increasing prevalence of kidney disease in the population, more kidney biopsies are being performed. The aim of our study is to analyze clinical and histological characteristics of patients with active solid organ malignancy who underwent kidney biopsy. This is a multi-center collaborative retrospective study supported by groups GLOSEN/Onconephrology from the Spanish Society of Nephrology. Clinical, demographical and histological data were collected. Results: A total of 148 patients with cancer who underwent a kidney biopsy from 12 hospitals were included. 64.3% men and mean age of 66.9 years old. The indications for biopsy were acute renal injury (67.1%), proteinuria (17.1%), exacerbated chronic kidney disease (8.2%), and chronic kidney disease (7.5%). Most frequent malignances were lung (29.1%) and abdominal (25%), with 49.7% metastatic cancer. As oncospecific treatment, 28% received chemotherapy, 29.3% immunotherapy, 19.3% specific therapies, and 2.1% conservative treatment. At the time of kidney biopsy, median creatinine was of 2.58 mg/dL [1.81–4.1 (IQ 25–75)], median urine protein-to-creatinine ratio of 700 mg/g [256–2463 (IQ 25–75)] and 53.1% presented hematuria. The most frequent renal biopsy diagnoses were: acute interstitial nephritis (39.9%), acute tubular necrosis (8.8%), IgA nephropathy (7.4%) and membranous nephropathy (6.1%). Median follow-up was 15.2 months [5.7–31.4 (IQ 25–75)]. Conclusions: There is a new trend in kidney disease and cancer patients in terms of diagnosis and treatment. Acute interstitial nephritis has established itself as the most common kidney injury in patients with cancer who underwent a kidney biopsy. Renal biopsy is a valuable tool for diagnosis, treatment, and prognosis of solid organ cancer patients with kidney damage.This work was supported by grants from Fondo de Investigación Sanitaria-FEDER, ISCIII, Río Hortega CM20/00111, PI17/00257, PI21/01292, Marató TV3 2020 421/C/2020, Marató TV3 2021 215/C/2021, RD16/0009/0030 (REDINREN), EIN2020-1123381, and RD21/0005/0016 (RICORS 2040)

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)

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

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

Enteric Budesonide in Transplant and Native IgA Nephropathy: Real-World Clinical Practice

Budesonide; Transplant; NephropathyBudesonida; Trasplante; NefropatíaBudesonida; Trasplantament; Nefropati

Acute tubulointerstitial nephritis induced by checkpoint inhibitors versus classical acute tubulointerstitial nephritis: are they the same disease?

Nefritis tubular aguda; Biòpsia de ronyó; Teràpia amb esteroidesNefritis tubular aguda; Biopsia de riñón; Terapia con esteroidesAcute tubular nephritis; Kidney biopsy; Steroid therapyBackground The incidence of acute tubulointerstitial nephritis (ATIN) related to drugs has dramatically increased over recent years. A new subtype of ATIN, apparently different from classical drug-related ATIN, has emerged that has been related to the administration of immune checkpoint inhibitors (ICIs). We investigated these differences between ICI-related ATIN (ICI ATIN) and non-ICI-related ATIN in terms of clinical features, response to treatment with steroids and the evolution of kidney function. Methods A total of 47 patients diagnosed with ATIN from two centres were recruited. Of these, 13 patients presented with ATIN during ICI treatment and 34 were diagnosed with ATIN attributed to other drugs. The main demographic, clinical and analytical variables such as gender, age and current medication were recorded. The type of malignancy, oncological treatment, ICI dose and presence of extrarenal immune-related adverse events were also reviewed. Renal biopsy diagnosis, time to drug withdrawal and ATIN-specific treatment, as well as laboratory data during follow-up, were also studied. Results Patients diagnosed with ICI ATIN presented with lower creatinine (ICI ATIN 3.8 ± 1.03  versus classical ATIN 5.98 ± 4.15 mg/dL, P = 0.007) at diagnosis and higher urinary leucocyte counts (ICI ATIN 263.2 ± 418.04 versus classical ATIN 133.55 ± 284.62, P = 0.048) compared with patients with non-ICI-related ATIN. Time from initiation of the culprit drug to ATIN diagnosis was longer in patients with ICI ATIN than in those with classical ATIN (197.07 ± 184.99 versus 114.4 ± 352.16 days, P = 0.006). In addition, during follow-up, the slope of decreasing creatinine over time was lower for ICI ATIN compared with non-ICI-related ATIN. Conclusions In this study, we analysed differences between ICI ATIN and classical ATIN. We found that patients with ICI ATIN presented with a larger latency period after culprit drug initiation, milder acute kidney injury and slower creatinine amelioration compared with those with classical ATIN. These results may, in part, be ascribed to potential differences in the pathological mechanisms involved in ATIN development, suggesting that ICI and classical ATIN may be different diseases with similar renal histologies.We gratefully acknowledge the support of FIS/Fondos FEDER (REDinREN RD016/0009)