Background: The efficacy and safety of rituximab (RTX) in adult frequent-relapsing (FR) or steroid-dependent (SD) nephrotic syndrome (NS), including minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS), are still inconclusive. Methods: We performed a systematic review and meta-analysis registered in PROSPERO (CRD42019148102) by pooling data of cohort studies or case series on adult patients with difficult-to-treat NS. Steroid-resistant NS was excluded. The primary outcomes were the complete remission (CR) rate and the relapse rate. Partial remission (PR) rate, no response (NR) rate and adverse events were the secondary outcomes. A random-effects model was performed for all the outcomes. Results: We included 21 studies involving 382 adult MCD/FSGS subjects with a median follow-up duration from 12 to 43 months. RTX treatment induced a pooled 84.2% CR rate [95% confidence interval (CI): 67.7–96.3%], while MCD patients had a high 91.6% CR rate and FSGS patients a moderate 43% CR rate. However, 27.4% (95% CI 20.7–34.5%) of the patients relapsed during the follow-up. The pooled PR and NR rates were 5.8% (95% CI 1.2–12.5%) and 5.2% (95% CI 0.0–15.0%), respectively. RTX was associated with trivial adverse events and good tolerance. Conclusions: In summary, by pooling results of current pilot studies, RTX may be an effective and relatively safe alternative for most adult FR or SD MCD/FSGS to displace calcineurin inhibitors or prednisone in the hierarchy of treatment. More clinical trials comparing RTX with other immunosuppressants and concerning the long-term adverse events are needed.

Background: This network meta-analysis investigated the effect of various combined regimens of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and renin-angiotensin-aldosterone system inhibitors (RAASis) on the occurrence of hyperkalemia in diabetic kidney disease. Methods: The risk of hyperkalemia was compared using the random-effects model of network meta-analysis, with results expressed as odds ratios (ORs) with 95% confidence intervals (CIs). The comparative effects of all medications and their combinations with placebo were ranked using the surface under the cumulative ranking probabilities. Results: In total, 27 eligible studies involving 43,589 participants with diabetic kidney disease were included. Major findings showed that the use of mineralocorticoid receptor antagonists (MRAs) on top of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) prominently increased hyperkalemia incidence when compared with placebo (OR, 6.08; 95% CI, 2.30 to 16.08), ACEI (OR, 3.07; 95% CI, 1.14 to 8.31), ARB (OR, 2.57; 95% CI, 1.10 to 6.02), SGLT2i (OR, 9.22; 95% CI, 2.99 to 28.46), renin inhibitors+ACEI/ARB (OR, 2.23; 95% CI, 1.14 to 4.36), or SGLT2i+ACEI/ARB (OR, 4.10; 95% CI, 2.32 to 7.26). Subgroup analysis among different generations of MRA found that spironolactone had the strongest effect in combination with ACEI/ARB, even higher than the combined use of ACEI and ARB (OR, 2.89; 95% CI, 1.26 to 6.63). In addition, SGLT2i had a significantly lower incidence of hyperkalemia compared with ACEI (OR, 0.33; 95% CI, 0.12 to 0.91), ARB (OR, 0.28; 95% CI, 0.13 to 0.61), dual RAASi (ACEI combined with ARB; OR, 0.17; 95% CI, 0.06 to 0.47), or MRA or renin inhibitors combined with ACEI/ARB (OR, 0.11; 95% CI, 0.04 to 0.33; OR, 0.24; 95% CI, 0.08 to 0.76, respectively). Moreover, adding SGLT2i to the combination of MRA and ACEI/ARB, as well as the combinations of different RAASis, markedly reduced the occurrence of hyperkalemia. Conclusions: Among the therapeutic drugs with the potential risk of increasing serum potassium in patients with diabetic kidney disease, MRA added an extra risk of hyperkalemia while SGLT2i had the opposite effect and could even reverse the elevation of serum potassium caused by the combined regimen, including MRAs.

Background: Peritoneal dialysis (PD) patients are at high risk of developing glucose metabolism disturbance (GMD). The incidence and prevalence of new-onset GMD, including diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fast glucose (IFG), after initiation of PD, as well as their correlated influence factors, varies among studies in different areas and of different sample sizes. Also, the difference compared with hemodialysis (HD) remained unclear. Thus we designed this meta-analysis and systematic review to provide a full landscape of the occurrence of glucose disorders in PD patients. Methods: We searched the MEDLINE, Embase, Web of Science and Cochrane Library databases for relevant studies through September 2018. Meta-analysis was performed on outcomes using random effects models with subgroup analysis and sensitivity analysis. Results: We identified 1124 records and included 9 studies involving 13 879 PD patients. The pooled incidence of new-onset DM (NODM) was 8% [95% confidence interval (CI) 4–12; I2 = 98%] adjusted by sample sizes in PD patients. Pooled incidence rates of new-onset IGT and IFG were 15% (95% CI 3–31; I2 = 97%) and 32% (95% CI 27–37), respectively. There was no significant difference in NODM risk between PD and HD [risk ratio 0.99 (95% CI 0.69–1.40); P = 0.94; I2 = 92%]. PD patients with NODM were associated with an increased risk of mortality [hazard ratio 1.06 (95% CI 1.01–1.44); P < 0.001; I2 = 92.5%] compared with non-DM PD patients. Conclusions: Around half of PD patients may develop a glucose disorder, which can affect the prognosis by significantly increasing mortality. The incidence did not differ among different ethnicities or between PD and HD. The risk factor analysis did not draw a definitive conclusion. The glucose tolerance test should be routinely performed in PD patients.

Background: The different clinical characteristics of community-acquired acute kidney injury (CA-AKI) versus hospital-acquired AKI (HA-AKI) have remained inconclusive, and thus, a meta-analysis was conducted to summarize and quantify the clinical significance distinguishing the 2 types of AKI. Methods: We identified observational studies reporting the clinical characteristics and prognosis of HA-AKI and CA-AKI. ORs and mean differences (MDs) were extracted for each outcome and the results aggregated. The primary outcome was defined as the mortality rate; renal recovery, oliguria incidence, dialysis, intensive care unit (ICU) requirement, and length of hospital stay were secondary outcomes. Results: Fifteen eligible studies involving 46,157 patients (22,791 CA-AKI patients and 23,366 HA-AKI patients) were included. Mortality was significantly lower in CA-AKI than in HA-AKI patients, with an OR of 0.43 (95% CI 0.35–0.53). The incidence of oliguria and need for ICU were also lower in CA-AKI patients (OR 0.58, 95% CI 0.38–0.88; OR 0.24, 95% CI 0.14–0.40, respectively). CA-AKI patients had a shorter hospital stay (MD –9.42, 95% CI –13.73 to –5.12). The renal recovery rate and dialysis need between CA- and HA-AKI were similar (OR 1.27, 95% CI 0.53–3.02; OR 1.05, 95% CI 0.82–1.34, respectively). Conclusions: CA-AKI showed better clinical manifestations with a lower incidence of oliguria, reduced risk of ICU treatment, and shorter hospital stay. Mortality associated with CA-AKI was lower compared with HA-AKI, indicating a better prognosis. The rate of renal recovery and need for dialysis showed no significant difference between the 2 groups.