Chronic kidney disease (CKD) has been recognized as a leading public health problem worldwide. Through its effect on cardiovascular risk and end-stage kidney disease, CKD directly affects the global burden of morbidity and mortality. Classical optimal management of CKD includes blood pressure control, treatment of albuminuria with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, avoidance of potential nephrotoxins and obesity, drug dosing adjustments, and cardiovascular risk reduction. Diabetes might account for more than half of CKD burden, and obesity is the most important prompted factor for this disease. New antihyperglycemic drugs, such as sodium-glucose-cotransporter 2 inhibitors have shown to slow the decline of GFR, bringing additional benefit in weight reduction, cardiovascular, and other kidney outcomes. On the other hand, a new generation of non-steroidal mineralocorticoid receptor antagonist has recently been developed to obtain a selective receptor inhibition reducing side effects like hyperkalemia and thereby making the drugs suitable for administration to CKD patients. Moreover, two new potassium-lowering therapies have shown to improve tolerance, allowing for higher dosage of renin-angiotensin system inhibitors and therefore enhancing their nephroprotective effect. Regardless of its cause, CKD is characterized by reduced renal regeneration capacity, microvascular damage, oxidative stress and inflammation, resulting in fibrosis and progressive, and irreversible nephron loss. Therefore, a holistic approach should be taken targeting the diverse processes and biological contexts that are associated with CKD progression. To date, therapeutic interventions when tubulointerstitial fibrosis is already established have proved to be insufficient, thus research effort should focus on unraveling early disease mechanisms. An array of novel therapeutic approaches targeting epigenetic regulators are now undergoing phase II or phase III trials and might provide a simultaneous regulatory activity that coordinately regulate different aspects of CKD progression.

<b><i>Background:</i></b> Acute interstitial nephritis (AIN) is one of the chief causes of acute kidney injury (AKI). AIN might be produced by drugs, infections, autoimmune diseases, or can be idiopathic. Among these etiologies, drug-induced AIN (DI-AIN) is the dominant one in many countries. Even when DI-AIN is suspected, identification of the putative drug is challenging. <b><i>Summary:</i></b> DI-AIN is an increasingly common cause of AKI. Diagnosis continues to pose a challenge for physicians due to nonspecific clinical symptoms, and the fact that it can be triggered by a wide variety of medications. Furthermore, the gold standard for the diagnosis is kidney biopsy. All these aspects render the diagnosis more difficult. The withdrawal of the causative drug of DI-AIN is the centerpiece of the treatment, and if early restoration of original kidney function is not obtained, several studies support the treatment with steroids especially when they are started quickly. <b><i>Key Messages:</i></b> Almost all drugs have the potential to produce drug-induced acute interstitial nephritis (DI-AIN); however, antibiotics, nonsteroidal anti-inflammatory agents, and proton pump inhibitors account for the majority of the reported cases. DI-AIN is produced by an idiosyncratic delayed type IV hypersensitivity reaction, but the precise pathophysiological mechanism remains to be elucidated. DI-AIN symptoms are nonspecific, and most of the patients will present mild symptoms including malaise, nausea, and vomiting. The classical triad, associating fever, rash, and eosinophilia, is seldom present. Nonoliguric acute kidney injury is the main renal manifestation of DI-AIN. Tubular nonnephrotic range proteinuria is usually present. Diagnosis of DI-AIN relies on maintaining a high index of suspicion in those patients at greater risk, but kidney biopsy is required to confirm diagnosis. Histologically, AIN is characterized by the presence of an extensive interstitial infiltrate, mainly composed of lymphocytes and monocytes, but eosinophils, plasma cells, histiocytes, and polymorphonuclear cells can also be found. The withdrawal of the presumed causative drug of DI-AIN is the mainstay of the treatment. When there is no evidence of kidney function recovery after an interval of 5–7 days since interrupting the treatment with the suspected drug, several studies support the treatment with steroids, especially when they are promptly started. Early corticosteroids would decrease the inflammatory infiltrates of the kidney interstitium, thus preventing the risk of subsequent fibrosis.

Introduction There is an increased risk of thrombotic complications in patients with COVID‐19. Hemodialysis patients are already at an increased risk for thromboembolic events such as stroke and pulmonary embolism. The aim of our study was to determine the incidence of late thrombotic complications (deep vein thrombosis, pulmonary embolism, stroke, new‐onset vascular access thrombosis) in maintenance hemodialysis patients after recovery from COVID‐19. Methods We performed a retrospective cohort study of 200 prevalent hemodialysis patients in our center at the start of the pandemic. We excluded incident patients after the cohort entry date and those who required hemodialysis for acute kidney injury, and excluded patients with less than 1 month follow‐up due to kidney transplantation or death from non‐thrombotic causes. Findings One‐hundred and eighty five prevalent hemodialysis patients finally met the inclusion criteria; 37 patients (17.6%) had SARS‐CoV‐2 infection, out of which 10 (27%) died during the acute phase of disease without evidence of thrombotic events. There was an increased risk of thrombotic events in COVID‐19 survivors compared to the non‐infected cohort (18.5% vs. 1.9%, p = 0.002) after a median follow‐up of 7 months. Multivariate regression analysis showed that COVID‐19 infection increased risk for late thrombotic events adjusted for age, sex, hypertension, diabetes, antithrombotic treatment, and previous thrombotic events (Odds Ratio (OR) 26.4, 95% confidence interval 2.5–280.6, p = 0.01). Clinical and laboratory markers did not predict thrombotic events. Conclusions There is an increased risk of late thrombotic complications in hemodialysis patients after infection with COVID‐19. Further studies should evaluate the benefit of prolonged prophylactic anticoagulation in hemodialysis patients after recovery from COVID‐19.

Background Kidney fibrosis has been reported to be a prognostic factor in CKD progression. Previous studies have shown that the assessment of urinary Dickkopf-3 (uDKK3), a stress induced tubular epithelial-derived profibrotic glycoprotein, might be a potential tubulointerstitial fibrosis biomarker and might identify patients at short-term risk of eGFR loss. We aim to evaluate uDKK3 as a potential biomarker for progression of CKD in a cohort with various etiologies of CKD, and subsequently in an overt diabetic nephropathy cohort. Methods We prospectively studied two independent cohorts comprising a total of 351 patients with stage 2-3 CKD. Combined primary outcome consisted of a 50% increase in serum creatinine, ESKD or death. Progreser cohort included patients with heterogeneous etiologies and Pronedi cohort 101 patients with overt diabetic nephropathy. Median time of follow-up was 36 (30-39) and 36 (16-48) months, respectively. Results At baseline, median uDKK3 was 2200 (671 - 7617) pg/mg in the Progreser cohort and 3042 (661-9747) pg/mg in the Pronedi cohort. There were any statically significant differences in uDKK3 ratio between both cohorts, nor between CKD etiologies. Baseline uDKK3 was significantly higher in patients who reached primary outcome. In the Cox proportional-hazard model, the highest levels of uDKK3 were found to be an independent factor for renal progression in Progreser cohort (HR 1.91, CI95% 1.04 - 3.52) and in Pronedi cohort (HR 3.03, CI95% 1.03-8.92). uDKK3 gradually increased in the following months, especially in patients with higher proteinuria. Treatment with RAAS-blockers did not modify uDKK3 after 4 nor 12 months of treatment. Conclusions uDKK3 identifies patients at high risk of CKD progression regardless of the cause of kidney injury. uDKK3 might serve as a useful biomarker for kidney disease progression and therefore could be used by clinicians to optimize staging for renal progression and monitor the response to potential treatments.

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