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Background Current first-line anti-proteinuric treatments for nephrotic syndrome (NS) do not produce an effective response in all patients and are not tolerated by some patients. Additional effective and tolerable treatment options in NS are strongly needed. This retrospective case series is the largest to date to examine Acthar gel (adrenocorticotropic hormone, ACTH) in patients with varied-etiology NS. Methods This multicenter retrospective case series included adult patients with NS ( N  = 44) treated with Acthar gel at 6 clinical practices. NS etiologies included idiopathic focal segmental glomerulosclerosis (FSGS, 15), idiopathic membranous nephropathy (iMN, 11), IgA nephropathy (IgAN, 5), diabetic nephropathy (DN, 4), systemic lupus erythematosus class V membranous lupus nephritis (MLN, 2), minimal change disease (MCD, 2), membranoproliferative glomerulonephritis (MPGN, 1), fibrillary glomerulonephritis (FGN, 1), and unbiopsied NS (3). Proteinuria response was assessed as percent reduction from baseline and percent of patients meeting complete remission (final proteinuria <500 mg/d), partial remission (≥50 % reduction in proteinuria from baseline and final proteinuria 500–3500 mg/d), clinical response (≥30 % reduction in proteinuria from baseline that did not meet criteria for complete or partial remission), and no response (failed to meet remission or clinical response criteria) following Acthar gel therapy. Safety and tolerability were examined using adverse event (AE) frequency reported by patients or treating nephrologists and frequency of early discontinuation of treatment due to AEs. Results 68.2 % (30/44) of patients had received prior NS treatment with immunosuppressive or cytotoxic therapies. Thirty-seven patients completed Acthar gel treatment. Seven patients (15.9 %) had early termination due to AEs, including weight gain (2), hypertension (2), edema (1), fatigue (1), seizures (1) and for reasons not stated (2). Proteinuria reduction ≥30 % was shown in 81.1 % (30/37) of patients and 62.2 % (23/37) showed ≥50 % proteinuria reduction. Proteinuria responses were greatest in MCD ( n  = 2/2 complete remission), MLN ( n  = 2/2 partial remission), MPGN ( n  = 1/1 partial remission), FSGS ( n  = 12/15 [80.0 %] partial remission or clinical response), and iMN ( n  = 8/11 [72.7 %] complete remission, partial remission, or clinical response). Conclusions Acthar gel may meet an important treatment need in patients with treatment-resistant NS in response to first-line therapies, patients unable to tolerate first-line therapies, and in patients with advanced disease.

Current guidelines recommend under 2g/day sodium intake in chronic kidney disease, but there are a few studies relating sodium intake to long-term outcomes. Here we evaluated the association of mean baseline 24-h urinary sodium excretion with kidney failure and a composite outcome of kidney failure or all-cause mortality using Cox regression in 840 participants enrolled in the Modification of Diet in Renal Disease Study. Mean 24-h urinary sodium excretion was 3.46g/day. Kidney failure developed in 617 participants, and the composite outcome was reached in 723. In the primary analyses, there was no association between 24-h urine sodium and kidney failure (HR 0.99 (95% CI 0.91–1.08)) nor on the composite outcome (HR 1.01 (95% CI 0.93–1.09)), each per 1g/day higher urine sodium. In exploratory analyses, there was a significant interaction of baseline proteinuria and sodium excretion with kidney failure. Using a two-slope model, when urine sodium was under 3g/day, higher urine sodium was associated with increased risk of kidney failure in those with baseline proteinuria under 1g/day and with lower risk of kidney failure in those with baseline proteinuria of ⩾1g/day. There was no association between urine sodium and kidney failure when urine sodium was⩾3g/day. Results were consistent using first baseline and time-dependent urinary sodium excretion. Thus, we noted no association of urine sodium with kidney failure. Results of the exploratory analyses need to be verified in additional studies and the mechanism explored.

The alternative complement pathway plays a key role in the pathogenesis of IgA nephropathy. Iptacopan specifically binds to factor B and inhibits the alternative pathway. In this phase 3, double-blind, randomized, placebo-controlled trial, we enrolled adults with biopsy-confirmed IgA nephropathy and proteinuria with a 24-hour urinary protein-to-creatinine ratio of 1 or higher (with protein and creatinine both measured in grams) despite optimized supportive therapy. Patients were randomly assigned, in a 1:1 ratio, to receive oral iptacopan (200 mg) or placebo twice daily for 24 months while continuing to receive supportive therapy. The primary objective of this prespecified interim analysis was to assess the efficacy of iptacopan as compared with that of placebo in reducing proteinuria at month 9; the primary end point was the change from baseline in the 24-hour urinary protein-to-creatinine ratio at month 9. The proportion of patients who had a 24-hour urinary protein-to-creatinine ratio of less than 1 at month 9 without receiving rescue or alternative medication or undergoing kidney-replacement therapy (dialysis or transplantation) was a secondary end point. Safety was also assessed. The effect of iptacopan on kidney function will be assessed at the end of the 2-year double-blind treatment period. The main trial population included 222 patients in the iptacopan group and 221 in the placebo group. The interim efficacy analysis included the first 250 patients who underwent randomization in the main trial population (125 patients in each group) and who remained in the trial until month 9 or discontinued the trial by month 9. Safety was assessed in all the patients in the main trial population. At month 9, the adjusted geometric mean 24-hour urinary protein-to-creatinine ratio was 38.3% (95% confidence interval, 26.0 to 48.6; two-sided P<0.001) lower with iptacopan than with placebo. The reduction in proteinuria was supported by consistent results in secondary end point analyses. There were no unexpected safety findings with iptacopan. The incidence of adverse events that occurred during the treatment period was similar in the two groups; most events were mild to moderate in severity and reversible. No increased risk of infection was observed. Among patients with IgA nephropathy, treatment with iptacopan resulted in a significant and clinically meaningful reduction in proteinuria as compared with placebo. (Funded by Novartis; APPLAUSE-IgAN ClinicalTrials.gov number, NCT04578834.).

Objectives We aimed to evaluate the safety and efficacy of cotrimoxazole for preventing infections in patients with glomerulonephritis (GN) receiving rituximab (RTX) therapy. Study design and methods This single-center, open-label randomized controlled trial enrolled 150 patients with GN who received RTX at Xijing Hospital between October 2022 and December 2023. Participants were randomized 1:1 to either the cotrimoxazole prophylaxis group ( n  = 75) or the non-cotrimoxazole group ( n  = 75). The primary endpoint was the cumulative incidence of infection over a 180-day follow-up period. Secondary endpoints included the incidence of severe infections and the rate of adverse events (AEs) attributed to cotrimoxazole. Intervention All patients received RTX at a dose of 1000 mg intravenously on days 1 and 14. CD19 + B-cell counts were monitored monthly for 6-month post-initial infusion; if CD19 + B cells remained detectable at the 6-month mark, an additional 1000-mg RTX dose was administered. Cotrimoxazole prophylaxis protocol Patients in the intervention group initiated oral cotrimoxazole on the same day as their first RTX infusion, with one tablet daily for seven consecutive days. Prophylaxis was repeated for 7 days following each subsequent RTX infusion, resulting in a total of 14 days of prophylaxis over the study period. The non-cotrimoxazole group They received no cotrimoxazole prophylaxis. Results Over 180 days of follow-up, 8 infectious episodes occurred in 7 patients in the cotrimoxazole group, compared with 19 episodes in 16 patients in the control group. The annualized incidence density of infections (per 100 person-years) was 20.80 (95% CI 11.36–30.24) in the cotrimoxazole group versus 54.83 (95% CI 43.09–66.57) in the control group. The hazard ratio (HR) for the cumulative incidence of infection was 0.39 (95% CI 0.17–0.88; log-rank test, P  = 0.029), indicating a significant reduction in infection risk with cotrimoxazole prophylaxis. Conclusions Our findings demonstrate that cotrimoxazole prophylaxis for 1-week post-RTX infusion effectively prevents post-RTX infectious complications, reduces infection-related mortality, and does not elevate the risk of serious AEs. However, it should be noted that this study was a single-center investigation without a placebo control. Trial registration The study was registered on the Chinese Clinical Trial Registry (trial registration identifier: ChiCTR2200063564).

In this trial involving patients with IgA nephropathy, sibeprenlimab, a humanized IgG2 monoclonal antibody that blocks a proliferation-inducing ligand, resulted in a greater decrease in proteinuria than placebo.

In a prespecified interim analysis of a phase 3, randomized, controlled trial, the selective endothelin type A receptor antagonist atrasentan reduced proteinuria in patients with IgA nephropathy, without apparent safety issues.

Background Amelioration of proteinuria is one of main treatment targets in patients with glomerulonephritis, yet the remission rates are suboptimal. Aim of the study To examine the effect of the sodium–glucose transporter 2 inhibitor (empagliflozin) on proteinuria and kidney function progression, in patients with glomerulonephritis not due to diabetic kidney diseases. Subjects and methods Fifty patients were recruited. The entry criteria were diagnosis of glomerulonephritis, and proteinuria (proteinuria ≥ 500 mg⁄g) in spite of the use of the maximal tolerated dose of RAAS blocking agents together with specific immunosuppression treatment regimens. Group 1 (Empagliflozin arm): 25 patients who received 25 mg of empagliflozin once daily for 3 months as add-on to their regular treatment protocol (RAAS blockers and immunosuppression). Group 2 (Placebo arm): 25 patients treated with RAAS blockers and immunosuppression. The primary efficacy endpoints were the change in creatinine eGFR, and proteinuria 3 months after starting treatment. Results Progression of proteinuria was lower with empagliflozin as compared to placebo (odds ratio, 0.65; 95% CI, 0.55 to 0.72, p  = 0.002). Decline in eGFR was lower with empagliflozin as compared to placebo; however, this was statistically not significant (odds ratio, 0.84; 95% CI, 0.82 to 1.2, p  = .31). The percentage change in proteinuria was greater with empagliflozin as compared to placebo (median, − 77 (− 97–105) vs − 48 (− 80–117). Conclusion Empagliflozin has a favorable effect on amelioration of proteinuria in patients with glomerulonephritis. Empagliflozin has tendency to preserve kidney function in patients with glomerulonephritis as compared to placebo; however, longer term studies are required.

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a chronic, relapsing-remitting condition associated with increased morbidity. Previous research has shown patients with AAV report high levels of fatigue, pain, depression and anxiety. Over recent years successful work has been carried out to improve clinical outcomes, resulting in reduced mortality and end stage kidney disease (ESKD). Despite this, little work has been done to better understand the role of the patient within this condition. The prevalence of AAV is increasing and to date, there is a shortage of specific tools that assess and measure key features relating to patient reported outcomes (PROs). This protocol details how we can better understand the lived experiences of those with AAV through the development of a disease specific, patient reported outcome measure (PROM), to be used in clinic practice. This will allow us to recognise and validate PROs and the impact the disease and its treatment has on patients’ health related quality of life (HRQoL). In addition, we aim to identify potential differences in PRO’s between demographics, organ involvement and treatment subgroups in AAV as well as outcomes relating to the patient experience. Patients from a single centre in the UK will be recruited to take part in the exploratory qualitative study which will include focus groups and semi-structured interviews. The inclusion criteria comprise anyone with a diagnosis of AAV and willing to participate, including those who have active or relapsing disease, those are economically active, unemployed, retired and patients receiving renal replacement therapy. The aim of the project is to identify key issues patients experience in relation to their disease and its management and how these can be better assessed in a new PROM developed for use in the clinic setting. This will enable better delivery of individualised care and inform shared decision making, while also serving as a platform for future research looking at PROs in other glomerulonephritides.

Acute kidney injury (AKI) is common in anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA GN). Although ANCA GN has crescents in 90% of cases, the crescentic form occurs in only 20 to 30%, so it is challenging to attribute acute kidney injury (AKI) solely to the glomerular component. In contrast, IgA nephropathy (IgAN), while also frequently demonstrating crescent formation, is associated with a notably lower incidence and severity of AKI compared to ANCA GN. This discrepancy suggests that acute tubulointerstitial injury may constitute a more prominent-and previously underrecognized-contributor to AKI in ANCA GN. This study aimed to compare tubulointerstitial injury between ANCA GN and IgAN after matching for glomerular injury, and to assess its impact on AKI in ANCA GN. Propensity score matching were used to compare 48 ANCA GN patients and 48 IgAN patients, matched for age, sex, and glomerular injury parameters. We compared the disparities in tubulointerstitial injury in the renal pathology of ANCA GN and IgAN and analyzed the influence of tubulointerstitial injury on AKI in ANCA GN. ANCA GN had more severe acute tubulointerstitial injury, alongside higher serum creatinine (  = 0.048) and AKI incidence (31.3% vs 4.2%,  < 0.001) than IgAN. In patients with ANCA GN, whether the influence of glomerular injury is corrected, patients with interstitial cell infiltration > 25% exhibit higher levels of serum creatinine. Acute tubulointerstitial injury is a major contributor to AKI in ANCA GN, independent of glomerular injury, highlighting its clinical significance in the acute disease phase.

Background Kidney transplantation confers superior outcomes for patients with end stage kidney disease, and live donor kidneys associate with superior outcomes compared to deceased donor kidneys. Modern immunosuppression has improved rejection rates and transplant survival and, as a result, recurrence of glomerulonephritis has emerged as a major cause of allograft loss. However, many glomerulonephritides have significant genetic risk which may manifest through kidney intrinsic or systemic mechanisms. We hypothesise that heritable kidney intrinsic predisposition to glomerulonephritis will result in increased risk of glomerulonephritis recurrence in kidneys transplanted from genetically related donors. Methods We investigated the effect of living related donation on rates of recurrence and subsequent graft outcomes in 7236 patient from 28 years of ANZDATA transplant registry data. Data were analysed in R, using Kaplan Meier Survival analysis and adjusted analyses performed using Cox Proportional Hazards methods. A competing risk model was also analysed. Results Glomerulonephritis recurrence rates were significantly higher in living related donor grafts compared to either living unrelated or deceased donor grafts ( p  < 0 · 001). In IgA nephropathy, transplantation from living related donor kidneys demonstrated a 10 year recurrence rate of 16 · 7% compared to 7 · 1% in living unrelated donors and 9 · 2% in deceased donors (HR:1 · 7, 95% CI:1 · 26–2 · 26, p  = 0 · 0005 for living related vs deceased donors). In focal segmental glomerulosclerosis, risk of recurrence at 10 years was 14 · 6% in living related donors compared to 10 · 8% in living unrelated donors and 6 · 6% in deceased donors (HR:2 · 2, 95% CI 1 · 34–3 · 64, p  = 0 · 002) for living related vs deceased donors. Primary glomerulonephritis death censored graft survival was superior for living donor grafts, related or unrelated, compared to deceased donor grafts. Conclusions We identified a significant increase in the risk of glomerulonephritis recurrence in IgA Nephropathy and Focal Segmental Glomerulosclerosis in living related donors compared to a deceased donors.