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.
Background and Aims Arteriovenous fistula (AVF) is the best vascular access for hemodialysis. However, the role of preoperative isometric exercises in patients with advanced cronic kidney disease (CKD) who are candidates for AVF is unclear and not well reported in the literature. The main objetive of this study was to evaluate the effect of preoperative isometric exercise on vascular territory in advanced CKD prior to AVF creation. Method An 8 months prospective single-center study. We performed an isometric preoperative exercise program for 4 weeks on the non dominant arm (exercise arm) and was compared with the dominant arm (control arm) performing usual activity in our advanced CKD patients. Demographic data, upper limb muscle strength (ULMS), Doppler ultrasound (DUS) measurements (foream and distal cefalic vein (FCV, DCV) diameter, basilic vein (BV) diameter and depth, peak systolic velocities (PSVs) and diameters in the radial artery (RA) and braquial artery (BA), as well as percentage of patients candidates to AVF in both arm (exercise and control arm) according to Spanish Clinical Guidelines of Vascular Access (VA) and possible medical complications were analyzed. Results 27 patients. 67,7%men. Mean age 70,3±10,4years. Main cardiovascular risk factors: HBP (93,5%) and DM (64,5%). Exercise arm was left side in 87,1%. A significant increase was observed in ULMS only in exercise arm at the end of study (23,8±8,7Kg vs 27, 6±9,5Kg, p = 0,001). Related to DUS measurements, there were not diffences between groups on vein caliber. However, a significant increase was observed in RA PSV (57,7±15,3 vs 62,6±17,4cm/seg, p = 0,044), BA diameter (4,6±0,6 vs 4,9±0,9mm, p = 0,029) and percentage of patients who could be candidates to AVF (70,4 vs 92,6%, p = 0,034) in exercise arm at the end of the study. We did not observe any related complications (pain, hypotension or muscle injury). Conclusion Preoperative isometric exercises would increase the percentage of performing a native AVF in those advanced CKD patients candidates for HD. Similarly, our results suggest that preoperative isometric exercise could be a useful tool to improve the vascular territory, mainly arterial, in our patients. However, more studies are required to confirm our results.
Background: Immunotherapy has transformed cancer treatment in advanced malignancies. Increased survival compared with the standard of care has made immunotherapy a fundamental component of oncotherapeutics. Immune checkpoint inhibitors (ICI) trigger a stimulus to kill cancer cells. Immune-related adverse events (irAEs), derived from its potent stimulus, affect diverse organs. Acute interstitial nephritis (AIN) is the most frequent kidney irAE. Glomerulopathies, although rare, constitute a more challenging diagnosis and treatment. Case presentation: A 72-year-old man with lung adenocarcinoma treated with Bevacizumab and Atezolizumab. During treatment, he developed nephrotic syndrome. A diagnosis of a phospholipase A2 receptor positive primary membranous nephropathy associated with atezolizumab was made. After failing to respond to steroid therapy, treatment with rituximab was the preferred option. Eight months after being treated with rituximab and 10 months after atezolizumab was stopped, the patient maintained preserved renal function and negativization of anti-PLA2R was achieved. Proteinuria declined to half of its initial value 5 months following anti-PLA2R negativization. Conclusion: Monitoring proteinuria as well as declining kidney function in patients being treated with ICI is a valuable measure to determine an indication for a timely kidney biopsy and treatment.
Background and Aims Fibrillary glomerulonephritis (FGN) is a rare histological pattern. Electron microscopy is needed for diagnostic confirmation where predominantly mesangial fibrils are observed. To support the diagnosis; DNAJB9 is a biomarker that is 100% sensitive and 100% specific for FGN. To date, there is no defined therapeutic approach. Various immunosuppressants have been implemented to treat FGN showing poor renal response and approximately 50% progression to chronic kidney disease. Method Ambispective observational study. A protocol based on a bibliographic review was developed. The protocol included an induction therapy with methylprednisolone pulses (MTP), 500 mg a day for three days. Followed by oral prednisone at a dose of one mg/kg with an individual titration period considering the clinical evolution. Demographic, clinical, and pathological variables were extracted from the electronic health record. Results Case 1. Seventy-eight-year-old female. History of arterial hypertension (HT) treated with an angiotensin-converting enzyme inhibitor (ACEi). She debuted with a nephrotic syndrome characterized by proteinuria of 15 grams/day, hypoalbuminemia, and altered kidney function with creatinine (Cr) of 2.7 mg/dL. Secondary causes were rule out. The kidney biopsy showed mesangial expansion with mesangial deposition of IgG and C3 on the immunofluorescence. Congo red was negative. Positivity for DNAJB9 was observed. The electron microscopy (EM) showed 20-nanometer fibrils in the mesangium. The patient was initiated on the treatment protocol with a subsequent reduction of prednisone over a period of 24 weeks. Complete remission, defined as proteinuria <0.5g/day and reduction > 50% of Cr was achieved after 20 weeks of treatment. Case 2. Forty-seven-year-old female with a history of hypertension treated with ACEi. The patient presented with proteinuria 3.5g/d with a normal kidney function. Secondary causes were rule out. The kidney biopsy showed mesangial thickening with IgG, C3, C1q, Kappa, and lambda positivity on immunofluorescence. Congo red was negative. DNAJB9 was positive. An electron microscopy study showed randomly arranged mesangial fibrils. The treatment protocol was started. Prednisone was titrated over a period of 20 weeks. Partial remission was observed, defined by >50% reduction of proteinuria. Kidney function remained preserved. Conclusion Induction treatment based on steroid pulses followed by prednisone titration in patients with FGN with predominantly mesangial compromise was associated with a substantial reduction of proteinuria and stabilization of kidney function.
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