Acute kidney injury (AKI) is a rare but severe adverse event of immune checkpoint inhibitors (ICIs). With the increasing reports of ICIs, it's necessary to put new insights into ICIs-related AKI. We conducted a systematic review of randomized controlled trials(RCTs) and a real-world study by extracting data from the US FDA Adverse Event Reporting System (FAERS) database. We explored ICIs-related AKI events in RCTs available in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to August 2021. Meta-analysis was performed by using risk ratios (RRs) with 95 %CIs. In a separate retrospective pharmacovigilance study of FAERs, disproportionality was analyzed using the proportional reports reporting odds ratio (ROR) and information components (IC). A total of 79 RCTs (500,09 patients) were included, and ICIs were associated with increased risk of all-grade (RR = 1.37, 95 %CI:1.14-1.65) and high-grade AKI (RR = 1.60, 95 %CI:1.16-2.20). Results of subgroup analysis indicated that RR of ICI-related AKI did not vary significantly by cancer type, treatment regimen (monotherapy or combination of ICIs), study design (double-blind or open-label), individual ICIs and publication status (published or unpublished). FAERS pharmacovigilance data identified 1918 cases of AKI related to ICIs therapy. ICIs were significantly associated with over-reporting frequencies of AKI (ROR = 2.38, 95 %CI:2.27-2.49; IC = 1.22, 95 %CI:1.16-1.27). The median onset time of AKI was 48 days, 77.5 % of patients discontinued the use of ICIs, and 15.9 % of patients resulted in death. These data suggest that ICIs were significantly associated with increased risk of AKI in both trial settings and clinical practice.

Several risk factors of immune checkpoint inhibitors (ICIs)-associated acute kidney injury (AKI) have been reported sporadically. To identify the risk factors of ICIs-associated AKI in a large-scale population, therefore we conducted a systematic review and a real-world retrospective study. We search literature concerning risk factors of ICIs-associated AKI in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to January 2022. Meta-analysis was performed by using odds ratios (ORs) with 95%CIs. In a separate retrospective pharmacovigilance study by extracting data from US FDA Adverse Event Reporting System (FAERS) database, disproportionality was analyzed using the reporting odds ratio (ROR). A total of 9 studies (5927 patients) were included in the meta-analysis. The following factors were associated with increased risk of ICIs-associated AKI, including proton pump inhibitors(PPIs) (OR = 2.07, 95%CI 1.78–2.42), angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin receptor blockers (ARBs) (OR = 1.56, 95%CI 1.24–1.95), nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 1.29, 95%CI 1.01–1.65), diuretics (OR = 2.00, 95%CI 1.38–2.89), diabetes mellitus (OR = 1.28, 95%CI 1.04–1.57), genitourinary cancer (OR = 1.46, 95%CI 1.15–1.85), combination therapy of ICIs (OR = 1.93, 95%CI 1.25–2.97) and extrarenal immune-related adverse events(irAEs) (OR = 2.51, 95%CI 1.96–3.20). Furthermore, analysis from FAERS database verified that concurrent exposures of PPIs (ROR = 2.10, 95%CI 1.91–2.31), ACEIs/ARBs (ROR = 3.25, 95%CI 2.95–3.57), NSAIDs (ROR = 3.06, 95%CI 2.81–3.32) or diuretics (ROR = 2.82, 95%CI 2.50–3.19) were observed significant signals associated with AKI in ICIs-treated patients. Concurrent exposures of PPIs, ACEIs/ARBs, NSAIDs or diuretics, diabetes mellitus, genitourinary cancer, combination therapy, and extrarenal irAEs seem to increase the risk of AKI in ICIs-treated patients.

Purpose The administration of immune checkpoint inhibitors (ICIs) may lead to renal adverse events, notably including renal dysfunction. To early predict the probability of renal dysfunction after ICIs therapy, a retrospective case–control study was conducted. Methods Clinical information on ICIs-treated patients was collected. Multivariable logistic regression was applied to identify risk factors for renal dysfunction after ICIs treatment. Moreover, a nomogram model was developed and validated internally. Results A total of 442 patients were included, among which 35 (7.9%) experienced renal dysfunction after ICIs treatment. Lower baseline estimated glomerular filtration rate (eGFR) (OR 0.941; 95% CI 0.917 to 0.966; p<0.001), concurrent exposure of platinum(OR 4.014; 95% CI 1.557 to 10.346; p=0.004), comorbidities of hypertension (OR 3.478; 95% CI 1.600 to 7.562; p=0.002) and infection (OR 5.402; 95% CI 1.544 to 18.904; p=0.008) were found to be independent associated with renal dysfunction after ICIs treatment. To develop a predictive nomogram for the occurrence of renal dysfunction after ICIs treatment, the included cases were divided into training and validation groups in a ratio of 7:3 randomly. The above four independent risk factors were included in the model. The area under the receiver operating characteristic curves of the predictiive model were 0.822 (0.723–0.922) and 0.815 (0.699–0.930) in the training and validation groups, respectively. Conclusions Lower baseline eGFR, platinum exposure, comorbidities of hypertension and infection were predictors of renal dysfunction in ICIs-treated patients with cancer. A nomogram was developed to predict the probability of renal dysfunction after ICIs treatment, which might be operable and valuable in clinical practice.

Old, who were diagnosed with stages 1 and 2 CKD and had their serum 25-hydroxyvitamin D [25 (OH) D] measured, were included. Patients were divided into vitamin D deficient and non-deficient groups depending on the cutoff serum 25 (OH) D value of 37 nmol/L. Clinical and biochemical parameters were evaluated for associated factors of vitamin D deficiency by logistic regression. Results: A total of 118 patients were included, of which 62 (52.5%) were vitamin D insufficient and 47 (39.8%) were vitamin D deficient. Using multivariate binary logistic regression analysis, high serum level of gamma-glutamyl transpeptidase (GGT) (OR = 5.163; 95%CI, 1.105-24.130; P = 0.037), dyslipidemia (OR = 3.083; 95%CI, 1.029-9.243; P = 0.044), 24-hour urinary protein excretion (UPE) ≥3.5 g/24 hrs (OR = 5.010; 95%CI, 1.316-19.074; P = 0.018), and treatment with glucocorticoids (OR = 2.973; 95%CI, 1.093-8.084; P = 0.033) were independently associated with vitamin D deficiency. In addition, among different types of nephropathy, minimal change disease (MCD) had the highest incidence (85.7%) of vitamin D deficiency. Conclusion: Poor vitamin D status is common in patients with stages 1 and 2 CKD in southern China. The incidence of vitamin D deficiency is 39.8%. High serum GGT level, dyslipidemia, 24-hour UPE ≥3.5 g/24 hrs, and treatment with glucocorticoids are independent associated factors of vitamin D deficiency....

Proteinuria during treatment of immune checkpoint inhibitors (ICIs) was another renal adverse event besides from acute kidney injury. We aim to investigate the incidence and associated factors of proteinuria associated with ICIs. A case-control observational study about ICIs-treated cancer patients was conducted. Clinical and laboratory data at the baseline and during the follow-up was collected. Patients developed proteinuria during ICIs-treatment were classified to the proteinuria group. Between March 2019 and August 2022, 440 patients were included in the study. Forty-eight patients (10.9%) developed proteinuria after ICIs-treatment. The occurrence of acute kidney injury between the proteinuria group and the control showed no difference[1(2.1%) vs. 9(2.3%), p = 1.000]. By multivariable logistic analysis, accumulative cycle of ICIs-administration (OR 1.079, 95% CI 1.033 to 1.127, p = 0.001) and comorbidity of liver cirrhosis (OR 2.198, 95% CI 1.082 to 4.468, p = 0.030) were associated with occurrence of proteinuria after ICIs-treatment independently. Proteinuria could develop during the course of ICIs-therapy. Urinalysis should be monitored, especially for patients received multi-cycle of ICIs-administration and comorbid with liver cirrhosis.

Purpose: Idiopathic membranous nephropathy (IMN) with moderate risk or above was recommended to receive immunosuppressive therapy. We attempted to evaluate the optimal dose of glucocorticoid when combined with evidence-proven effective immunosuppressants by network meta-analysis. Methods: A systematic review of the literature was conducted in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception until January 2022. Randomized controlled trials (RCTs) in IMN limited to supportive care, glucocorticoids, cyclophosphamide, chlorambucil, calcineurin inhibitors (CNIs), and rituximab were screened. Results: Twenty-eight RCTs of 1,830 patients were included. Therapeutic regimens were divided as follows: moderate-to high-dose glucocorticoids plus CNIs (HMSCn), moderate-to high-dose glucocorticoids plus cyclophosphamide (HMSCt), moderate-to high-dose glucocorticoids plus chlorambucil (HMSCh), zero-to low-dose glucocorticoids plus CNIs (LNSCn), zero-to low-dose glucocorticoids plus cyclophosphamide (LNSCt), rituximab alone (R), glucocorticoids alone (SE), and supportive care alone (SP). Compared with SP, HMSCh (risk ratio [RR]: 1.77, 95% confidence interval [CI]: 1, 3.18), HMSCn (RR: 2.5, 95%CI: 1.25, 5.11), HMSCt (RR: 2.15, 95%CI: 1.29, 3.64), LNSCn (RR: 2.16, 95%CI: 1.25, 3.95), and R (RR: 2.07, 95%CI: 1, 4.39) had a higher probability of total remission rate, while HMSCn represented the highest probability depending on the surface under the cumulative ranking area (SUCRA) ranking values. Regarding infection, no significant difference was found between different doses of glucocorticoids plus the same immunosuppressant. HMSCn and HMSCt showed superiority in reducing 24-hour urine total protein compared with HMSCh, LNSCn, SE, and SP, while HMSCn seemed to be the most effective regimen through the ranking of SUCRA value. Conclusion: Moderate-to high-dose glucocorticoids showed superiority in proteinuria remission when combined with CNIs in IMN, with no increasing risk of infection.