Glomerular hematuria is a cardinal symptom of renal disease. Glomerular hematuria may be classified as microhematuria or macrohematuria according to the number of red blood cells in urine. Recent evidence suggests a pathological role of persistent glomerular microhematuria in the progression of renal disease. Moreover, gross hematuria, or macrohematuria, promotes acute kidney injury (AKI), with subsequent impairment of renal function in a high proportion of patients. In this pathological context, hemoglobin, heme, or iron released from red blood cells in the urinary space may cause direct tubular cell injury, oxidative stress, pro-inflammatory cytokine production, and further monocyte/macrophage recruitment. The aim of this manuscript is to review the role of glomerular hematuria in kidney injury, the role of inflammation as cause and consequence of glomerular hematuria, and to discuss novel therapies to combat hematuria.

Renal amyloidosis is one of the most severe complications of familial Mediterranean fever (FMF). Colchicine has reduced the incidence of this complication, which now only appears in untreated, under-treated and resistant patients, but it is usually ineffective in patients with advanced amyloidosis. Here we report a patient with FMF and biopsy-proven amyloidosis who presented with nephrotic syndrome despite colchicine treatment. Anakinra (an interleukin-1β inhibitor) was started and a dramatic complete remission of nephrotic syndrome was observed in the following months. Anakinra can be an effective treatment for FMF patients with severe secondary amyloidosis.

Macroscopic hematuria (MH) bouts, frequently accompanied by acute kidney injury (AKI-MH) are one of the most common presentations of IgA nephropathy (IgAN) in the elderly. Immunosuppressive therapies are used in clinical practice; however, no studies have analyzed their efficacy on kidney outcomes. This is a retrospective, multicenter study of a cohort of patients aged ≥50 years with biopsy-proven IgAN presenting with AKI-MH. Outcomes were complete, partial, or no recovery of kidney function at 1 year after AKI-MH, and kidney survival at 1, 2, and 5 years. Propensity score matching (PSM) analysis was applied to balance baseline differences between patients treated with immunosuppression and those not treated with immunosuppression. The study group consisted of 91 patients with a mean age of 65 ± 15 years, with a mean follow-up of 59 ± 36 months. Intratubular red blood cell (RBC) casts and acute tubular necrosis were found in all kidney biopsies. The frequency of endocapillary hypercellularity and crescents were low. Immunosuppressive therapies (corticosteroids alone or combined with mycophenolate mofetil or cyclophosphamide) were prescribed in 52 (57%) patients, whereas 39 (43%) received conservative treatment. There were no significant differences in the proportion of patients with complete, partial, or no recovery of kidney function at 1 year between patients treated with immunosuppression and those not treated with immunosuppression (29% vs. 36%, 30.8% vs. 20.5% and 40.4 % vs. 43.6%, respectively). Kidney survival at 1, 3, and 5 years was similar among treated and untreated patients (85% vs. 81%, 77% vs. 76% and 72% vs. 66%, respectively). Despite the PSM analysis, no significant differences were observed in kidney survival between the two groups. Fourteen patients (27%) treated with immunosuppression had serious adverse events. Immunosuppressive treatments do not modify the unfavorable prognosis of patients with IgAN who are aged ≥50 years presenting with AKI-MH, and are frequently associated with severe complications.

Background: The role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear. Methods: We conducted a retrospective single-center study including consecutive patients ≥65 years that developed severe COVID-19 between March 3 and May 1, 2020 and were treated with corticosteroids at various doses (methylprednisolone [0.5 mg/Kg/12 hours to 250 mg/24 hours]), either alone (“CS group”) or associated to intravenous tocilizumab (400-600 mg, one to three doses) (“CS-TCZ group”). Primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2-point decrease on a six-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied. Results: Overall, 181 and 80 patients were included in the CS and CS-TCZ groups. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17 – 0.68; P- value = 0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21 – 0.68; P -value = 0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21 – 0.72; P -value = 0.003). Clinical improvement by day +14 was higher in the CS-TCZ group in the IPTW analysis only (OR: 2.26; 95% CI: 1.49 – 3.41; P -value <0.001). The occurrence of secondary infection was similar between both groups. Conclusions: The combination of corticosteroids and TCZ was associated with better outcomes among patients ≥65 years with severe COVID-19.