Acute kidney injury as a risk factor for mortality in oncological patients receiving checkpoint inhibitors.

BACKGROUND: Checkpoint inhibitors (CPIs) have drastically improved metastatic cancer outcomes. However, immunotherapy is associated with multiple toxicities, including acute kidney injury (AKI). Data about CPI-related AKI are limited. Our aim was to determine risk factors for CPI-related AKI as well as its clinical characteristics and its impact on mortality in patients undergoing immunotherapy. METHODS: All patients under CPI at our centre between March 2018 and May 2019 and with a follow-up through April 2020 were included. Demographic, clinical and laboratory data were collected. AKI was defined according to the Kidney Disease: Improving Global Outcomes guidelines. We performed a logistic regression model to identify independent risk factors for AKI and actuarial survival analysis to establish risk factors for mortality in this population. RESULTS: A total of 759 patients were included, with a median age of 64 years. A total of 59% were men and baseline median creatinine was 0.80 mg/dL. The most frequent malignancy was lung cancer and 56% were receiving anti-programmed death protein 1 (PD-1). About 15.5% developed AKI during the follow-up. Age and baseline kidney function were identified as independent risk factors for CPI-related AKI. At the end of follow-up, 52.3% of patients had died. The type of cancer (not melanoma, lung or urogenital malignance), type of CPI (not cytotoxic T-lymphocyte-associated protein 4, PD-1, programmed death-ligand 1 or their combination) and the presence of an episode of AKI were identified as risk factors for mortality. CONCLUSIONS: A total of 15.5% of patients under immunotherapy presented with AKI. A single AKI episode was identified as an independent risk factor for mortality in these patients and age and baseline renal function were risk factors for the development of AKI.

COVID-19 in CKD Patients: Lessons from 553 CKD Patients with Biopsy-Proven Kidney Disease.

INTRODUCTION: Chronic kidney disease (CKD) patients infected with COVID-19 are at risk of serious complications such as hospitalization and death. The prognosis and lethality of COVID-19 infection in patients with established kidney disease has not been widely studied. METHODS: Data included patients who underwent kidney biopsy at the Vall d'Hebron Hospital between January 2013 and February 2020 with COVID-19 diagnosis during the period from March 1 to May 15, 2020. RESULTS: Thirty-nine (7%) patients were diagnosed with COVID-19 infection. Mean age was 63 ± 15 years and 48.7% were male. Hypertension was present in 79.5%, CKD without renal replacement therapy in 76.9%, and cardiovascular disease in 64.1%. Nasopharyngeal swab was performed in 26 patients; older (p = 0.01), hypertensive (p = 0.005), and immunosuppressed (p = 0.01) patients, those using RAS-blocking drugs (p = 0.04), and those with gastrointestinal symptoms (p = 0.02) were more likely to be tested for CO-VID-19. Twenty-two patients required hospitalization and 15.4% died. In bivariate analysis, mortality was associated with older age (p = 0.03), cardiovascular disease (p = 0.05), chronic obstructive pulmonary disease (p = 0.05), and low hemoglobin levels (p = 0.006). Adjusted Cox regression showed that low hemoglobin levels at admission had 1.81 greater risk of mortality. CONCLUSIONS: Patients with CO-VID-19 infection and kidney disease confirmed by kidney biopsy presented a mortality of 15.4%. Swab test for COVID-19 was more likely to be performed in older, hypertensive, and immunosuppressed patients, those using RAS-blocking drugs, and those with gastrointestinal symptoms. Low hemoglobin is a risk factor for mortality.

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

BACKGROUND: 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.

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

Novel 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.

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

BACKGROUND: 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.

Utility of transjugular renal biopsy as an alternative to percutaneous biopsy. / Biopsia renal transyugular. La alternativa a la biopsia percutánea en pacientes de alto riesgo.

BACKGROUND AND OBJECTIVES: Transjugular renal biopsies (TRB) are an alternative when percutaneous ultrasound renal biopsy is contraindicated. Few sites are currently carrying out this procedure, with limited literature existing on the indications, complications and diagnostic yield thereof. The aim of the study is to analyse the indications, diagnostic yield, safety and complications of percutaneous transjugular renal biopsies in our site over the last 15 years. MATERIAL AND METHODS: Retrospective descriptive study of all transjugular renal biopsies performed in our site, the Hospital Vall d'Hebron, between 2003 and 2018. For this, an exhaustive review of the clinical records of patients subjected to this procedure during the study period was conducted. RESULTS: 56 TRBs were performed during the study period. Out of the patients, 31 were men (55.4%) and 25 were women (44.6%), with a median age of 62 years (IQ range 25-75 [52.5-69.5]). More than half presented with haematuria at the time of biopsy, with a median creatinine of 2.69 mg/dL (IQ 25-75 [1.7-4.3]) and median proteinuria at 24 hours of 2000 mg (IQ 25-75 [0.41-4.77]).The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 140 +/- 26 mmHg and 75 +/- 15 mmHg, respectively. The biopsy was carried out owing to acute kidney failure in 19 patients, chronic kidney disease in 12 patients and nephrotic syndrome in 10 patients; in 15 patients it was carried out for other reasons. The most frequent TRB indication was technical impossibility in 16 of 56 cases (including infracostal kidneys, obesity and COPD), alterations in haemostasis (n = 6), thrombocytopenia (n = 5) and solitary kidney (n = 7). 12.5% of the biopsies were hepato-renal. Histological diagnoses were obtained in two thirds of the renal biopsies. The average number of cylinders obtained was 2.5 ± 1.3, with the average number of glomeruli being 6.6 ± 6.2. The most frequent histological diagnoses were IgA nephropathy, membranoproliferative glomerulonephritis and thrombotic microangiopathy. Three major complications were observed: fornix rupture and two transfusion requirements due to bleeding and subcapsular hematoma. CONCLUSIONS: In our site, TRB allowed for a histological diagnosis in 2/3 of patients for whom percutaneous ultrasound renal biopsy is contraindicated. This allowed us to diagnose and subsequently treat said patients.