Avoiding immunogenic drugs is key to preserve renal function in patients receiving immune checkpoint inhibitors: Lessons learned from three illustrative cases

Background: In the recent years, new immunotherapy agents are showing promising results in the treatment of cancer. Immune checkpoint inhibitors (ICI), which block neoplasm-induced lymphocyte inhibition and enhance cancer immunosurveillance mechanisms, are associated to acute tubulointerstitial nephritis (ATIN). The mechanisms of this adverse effect are debated. Methods: We present a three-case series of ATIN in the setting of ICI therapy managed in our Nephrology department. We detail the clinical course of the episodes, emphasizing on the concomitant medications administered. We also conducted a literature review of the altered drug immunogenicity in patients under immunotherapy drugs. Results: The three reported ATIN cases illustrate closer temporal association with the concomitant medication rather than the ICI itself. This suggests a scenario where the tolerance to previously accepted drugs seems to be lost. Moreover, one of the patients presented an ATIN flare after ICI discontinuation, suggesting an state of leukocyte hyperactivation. Conclusions: Unraveling the exact patho-mechanisms by which ICI-related ATIN occurs will allow the prevention of the development of this side effect and determine whether ICI re-challenge in patients previously affected by ICI-ATIN is safe.

Eplerenone Attenuates Fibrosis in the Contralateral Kidney of UUO Rats by Preventing Macrophage-to-Myofibroblast Transition

Severe renal fibrosis often occurs in obstructive kidney disease, not only in the obstructed kidney but also in the contralateral kidney, causing renal dysfunction. Although the mechanisms of injury in obstructed kidney have been studied for years, the pathogenesis of fibrosis in the contralateral kidney remains largely unknown. Here, we examined long-term unilateral ureteral obstruction (UUO) model in male Sprague–Dawley rats and found that macrophage-to-myofibroblast transition (MMT) is contributing to renal fibrosis in the contralateral kidney of UUO rats. Interestingly, this process was attenuated by treatment of eplerenone, a specific blocker of the mineralocorticoid receptor (MR). In-vitro, stimulating MR in primary cultured or cell line macrophages enhances MMT, which were also inhibited by MR blockade. Collectively, these findings provide a plausible mechanism for UUO-induced injury in the contralateral kidney, suggesting the benefit of using MR blockage as a part of treatment to UUO to protect the contralateral kidney thereby preserve renal function.

Understanding kidney injury in COVID-19; a pressing priority

The 2019 novel coronavirus disease (COVID-19) is a newly defined infectious and highly contagious acute disease caused by the severe acute respiratory syndrome coronavirus 2 ( (SARS-CoV-2). COVID-19 is mainly characterized by an acute respiratory disease however it can also affect multiple other organ systems such as the kidney, gastrointestinal tract, heart, vascular system, and the central nervous system. Kidney involvement is frequent in patients with COVID-19 and this review aims to explore the available data on kidney and COVID-19. In conclusion, COVID-19 infection can affect renal function and may cause acute kidney injury (AKI), due to several mechanisms that need to be fully elucidated. As only supportive management strategies are available for treating AKI in COVID-19, it is necessary to identify and preserve renal function during SARS-CoV-2 infection.

Tubulointerstitial nephritis and uveitis (TINU) syndrome and recent Streptococcus infection in a 9-year-old girl

A 9-year-old girl presented to hospital with a 6-week history of non-specific constitutional symptoms and weight loss. She initially underwent extensive medical investigation without diagnosis being achieved. Although raised inflammatory markers and impaired renal function were noted during her initial admission to hospital, it was her subsequent presentation 2 weeks later with sudden-onset bilateral anterior uveitis that prompted a renal biopsy that indicated acute tubulointerstitial nephritis. A diagnosis of tubulointerstitial nephritis and uveitis (TINU) syndrome was made and systemic glucocorticoid treatment initiated to prevent visual loss and preserve renal function. She has subsequently been reviewed in multidisciplinary outpatient clinics and treated with a tapering regimen of immunosuppressive therapy. Her treatment has been complicated by the side effects of glucocorticoids and by persistent relapses in ocular disease and abnormalities on urinalysis. Recent clinical investigations indicate that her uveitis is controlled and that renal function remains well preserved.

Antibody-Negative Relapse of Goodpasture Syndrome with Pulmonary Hemorrhage

Goodpasture syndrome is a rare autoimmune disease comprising antiglomerular basement membrane (anti-GBM) crescentic glomerulonephritis and pulmonary capillaritis with circulating anti-GBM antibodies. Rarely, antibody-negative cases have been described. We report a young, African American adult woman admitted with flank pain and hematuria with laboratory testing and kidney biopsy demonstrating anti-GBM crescentic glomerulonephritis with elevated anti-GBM antibody levels. She received treatment but remained dialysis-dependent. She was seronegative and clinically stable until she presented 8 months later with dyspnea and hemoptysis requiring mechanical ventilation. Bronchoscopy revealed diffuse alveolar hemorrhage. She was treated for relapse of Goodpasture syndrome. However, anti-GBM antibodies were undetectable. This case emphasizes prompt diagnosis and treatment of Goodpasture syndrome to preserve renal function. Additionally, clinical manifestations of Goodpasture syndrome and its degree of activity do not necessarily correlate with the actual antibody titer on relapse. Clinicians should have enhanced awareness of this atypical presentation of a rare disease.

Management of Ureteral Strictures and Ureteropelvic Junction Obstruction

The goals for management of ureteropelvic junction obstruction (UPJO) and ureteral stricture are to resolve obstruction, restore continuity, and preserve renal function while minimizing morbidity. The management of UPJO can be challenging and represents a spectrum of options that vary in the invasiveness and effective. These options include observation, long-term internal or external urinary drainage, and endoscopic or minimally invasive management. Mismanagement can potentially results in deterioration of loss of kidney function. This chapter discusses the foundations for successful management of UPJO and ureteral strictures. It also highlights the special clinical situations related to this disease entity and discusses the key advances in the field. This review contains 8 figures, 4 tables, and 73 references. Key Words: Boari flap, dismembered pyeloplasty, endopyelotomy, psoas hitch, pyeloplasty, ureteropelvic junction obstruction, ureteral obstruction, ureteral reconstruction, ureteral stricture, uretero-ureterostomy