To investigate the longitudinal changes in renal function and associated factors after intravitreal anti-vascular endothelial growth factor (VEGF) administration in diabetic macular edema (DME).
Methods
A total of 108 patients who had received intravitreal ranibizumab or aflibercept for DME and had follow-up visits for at least 2 years in one hospital were retrospectively enrolled. The estimated glomerular filtration rate (eGFR) at baseline and during the follow-up period and receipt of any renal replacement therapy were recorded. Linear regression and Cox regression models were used to evaluate factors associated with eGFR decline and renal replacement therapy.
Results
After intravitreal anti-VEGF treatment, eGFR showed a mean decline of −10.4 ± 23.2% and −16.5 ± 26.4% at months 12 and 24, respectively. Patients in the eGFR > 120 mL/min and 15–30 mL/min groups had the greatest decline (−32.0 ± 20.6% and −37.4 ± 30.9%, respectively) while those in the 61–90 mL/min group had the smallest decline (−4.3 ± 19.7%) in eGFR after the 2-year treatment. One out of 52 patients (1.9%) receiving ranibizumab and five out of 56 patients (8.9%) receiving aflibercept started hemodialysis or peritoneal dialysis within the 2-year follow-up period (P = 0.21). Baseline eGFR correlated with renal replacement therapy after intravitreal anti-VEGF treatment (hazard ratio = 0.879 per increase of 1 in eGFR, P = 0.018).
Conclusions
In DME patients receiving intravitreal anti-VEGF treatment, a persistent decline in eGFR was observed during the 2-year treatment course. Patients with extremely high or low eGFR had greater eGFR decline, and those with poor baseline eGFR tended to require dialysis after intravitreal anti-VEGF treatment.
Diabetic macular edema (DME) is the leading cause of visual impairment in diabetic patients, and diabetic nephropathy is often comorbid with diabetic retinopathy and DME.
Intravitreal anti-vascular endothelial growth factor (VEGF) injection is the most commonly used treatment for DME nowadays. However, the impact of intravitreal anti-VEGF injection on renal function has rarely been investigated.
In this study, we investigated the longitudinal changes in renal function and associated factors after intravitreal anti-VEGF for DME.
What was learned from this study?
After 2 years of intravitreal anti-VEGF treatment for DME, a mean decline of −16.5% in estimated glomerular filtration rate (eGFR) was observed, which was higher than expected in diabetic patients.
Patients with extremely high or low eGFR had greater eGFR decline, and those with poor baseline eGFR tended to require dialysis after intravitreal anti-VEGF treatment.
The potential adverse effect of intravitreal anti-VEGF in renal function might be underestimated. We recommend cautious monitoring of patients with poor renal function for changes in renal function after receiving intravitreal anti-VEGF therapy.
Introduction
Diabetic macular edema (DME) is one of the main causes of visual deterioration and vision loss in patients with diabetes [1]. The breakdown of the blood–retinal barrier is a key event in the progression of DME. This development encompasses a wide variety of cytokines under chronic hyperglycemia, in which the hypoxia-induced release of vascular endothelial growth factor (VEGF) plays an essential role [2]. VEGF inhibitors have revolutionized the therapeutic management of several retinal ophthalmic diseases, surpassing laser photocoagulation in terms of the ability to limit visual deterioration by increasing visual acuity in patients with DME [3]. Ranibizumab (0.3 mg or 0.5 mg, Lucentis; Genentech, South San Francisco, CA, USA; Novartis, Basel, Switzerland) is a humanized monoclonal antibody Fab fragment against VEGF-A [4, 5]. Aflibercept (2 mg, Eylea; Regeneron Pharmaceuticals, Tarrytown, NY, USA) is a fusion dimer with the constant region Fc of human immunoglobulin G1 (IgG1) [6]. Both intravitreal ranibizumab (IVR) and aflibercept (IVA) have shown anatomical and visual improvement in treating DME in several large randomized clinical trials [4, 5, 7]. Nowadays, these anti-VEGF drugs are considered optimal first-line treatment for DME [2].
Anzeige
Despite its harmful effects on diabetic eyes, VEGF plays an important role in renal pathophysiology, including glomerular podocytes, endothelial cells, and tubular epithelial cells [8]. Adverse effects on the kidneys, including proteinuria, nephrotic syndrome, hypertension, and acute kidney injury, have been noted when systemic anti-VEGF agents are used for treating cancers [9‐11]. As for intravitreal use, the anti-VEGF agents may also enter the systemic circulation and result in inhibition of systemic VEGF [12, 13]. Therefore, theoretically, intravitreal anti-VEGF treatment may also result in renal function impairment. Increased proteinuria after intravitreal bevacizumab has been noted in patients with preexisting diabetic nephropathy [14, 15]. Cases of decreased estimated glomerular filtration rate (eGFR) have also been reported after intravitreal injection of anti-VEGF including ranibizumab, aflibercept, and bevacizumab [16‐19]. However, few studies have focused on the longitudinal changes in renal function after intravitreal anti-VEGF therapy. Since diabetic nephropathy is often comorbid with diabetic retinopathy, the longitudinal change in eGFR after intravitreal anti-VEGF treatment for DME should be an important consideration. In this study, we investigated the longitudinal change in renal function in patients receiving IVR or IVA for DME for up to 2 years and evaluated the possible risk factors for renal function deterioration and renal replacement therapy after intravitreal anti-VEGF treatment.
Methods
Study Population
This study retrospectively enrolled patients who started treatment with IVR or IVA for DME at the National Taiwan University Hospital between January 2013 and December 2018. The inclusion criteria were as follows: (1) diabetic retinopathy documented by fundus photography or fluorescein angiography; (2) macular edema with the presence of retinal thickening, intraretinal cysts, or subretinal fluid, and central subfield thickness of > 300 μm as documented by optical coherence tomography (OCT); and (3) available record of eGFR at baseline (within 3 months before the first anti-VEGF injection) and during the 2-year follow-up period (at least two records at different time points after the first anti-VEGF injection). The exclusion criteria were as follows: (1) patients who did not receive regular follow-up visits and necessary treatments during the 2-year follow-up period, (2) patients with an eGFR ≤ 15 at baseline, (3) patients who had already received renal replacement therapy at baseline, and (4) patients who had previously received systemic or intravitreal anti-VEGF therapy. After recruitment, 108 patients were enrolled in this study, which was larger than the estimated sample size (n = 63) for a presumed eGFR change of −5 ± 10%. All patients received three consecutive monthly IVR or IVA injections as the loading treatment, which was aligned with the experts’ consensus in Taiwan [20], and then received treatment as needed at the physicians’ discretion after 3 months. This study adhered to the tenets of the Declaration of Helsinki, and approval was obtained from the institutional review board of the National Taiwan University Hospital (no. 202005058RINA). The need for informed consent was waived because of the retrospective nature of the study. The rule of confidentiality was followed during the study process, and no identifiable personal information is shown in this article.
Data Collection
Data were collected on age, sex, duration of diabetes, hypertension, insulin use, serum hemoglobin A1c (HbA1c), systolic blood pressure (SBP), serum creatinine at baseline and during the follow-up period, and receipt of renal replacement therapy including hemodialysis, peritoneal dialysis, hemofiltration, and renal transplantation during the 2-year follow-up period. eGFR was calculated using the equation recommended by the National Kidney Foundation in the Modification of Diet in Renal Disease Study. The baseline eGFR levels were then divided into five groups for analysis: > 120 mL/min, 91–120 mL/min, 61–90 mL/min, 31–60 mL/min, and 16–30 mL/min. The cumulative injection doses of anti-VEGF during the 2-year follow-up period were also recorded. All patients received either ranibizumab or aflibercept throughout the 2-year treatment courses. Therefore, only one type of anti-VEGF drug was used for each patient, and simultaneous bilateral injection was counted as two injections. Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) in OCT were collected at baseline and during the follow-up period, and OCT characteristics including intraretinal cyst (IRC), subretinal fluid (SRF), and ellipsoid zone disruption (EZD) at baseline were recorded.
Statistical Analysis
The eGFR data at months 3, 6, 12, 18, and 24 were recorded using the last observation carried forward method due to the individualized follow-up schedule. However, if the last observation time was longer than 3 months for month 6 or longer than 6 months for months 12, 18, and 24, the data were treated as missing. BCVA was converted to the logarithm of the minimum angle of resolution (logMAR) for analysis. The correlations between BCVA or OCT characteristics and eGFR groups were analyzed using t-tests or Fisher exact tests. Changes in eGFR and other systemic factors at different time points were calculated and compared with baseline using paired t-tests. For comparisons between the different baseline eGFR groups, t-tests were performed. Multiple linear regression analysis was used to evaluate the risk factors for eGFR decline. Multiple Cox regression models were used to evaluate risk factors for dialysis after anti-VEGF treatment. A P value of < 0.05 was considered statistically significant. SAS 9.4 software (SAS Institute Inc., Cary, NC, USA) was used for all statistical analyses.
Anzeige
Results
Baseline Characteristics
The mean age of the 108 patients was 65.4 ± 9.4 years (range 36–84 years); 49 were female, and 59 were male. Two patients (1.9%) had type 1 diabetes, and the other 106 (98.1%) had type 2 diabetes. Among the 108 patients, 52 received intravitreal injections of ranibizumab and 56 received aflibercept for treating DME. The mean eGFR at baseline was 67.6 ± 34.0 mL/min (range 17–188 mL/min). A total of 10, 14, 32, 40, and 12 patients had baseline eGFR of > 120 mL/min, 91–120 mL/min, 61–90 mL/min, 31–60 mL/min, and 16–30 mL/min, respectively. Other systemic parameters are shown in Table 1. At baseline, the mean logMAR of BCVA was 0.69 ± 0.36, and the mean CFT was 433.3 ± 142.9 μm. No significant differences in BCVA, CFT, IRC, SRF, or EZD were noted among the different eGFR groups (Supplementary Table 1).
Table 1
Demographic data and systemic characteristics at baseline
Mean ± SD or case number (%)
Age (years)
63.4 ± 9.4
Sex, female
49 (45.4%)
Type 1 diabetes/type 2 diabetes
2 (1.9%)/106 (98.1%)
Duration of diabetes (years)
16.6 ± 9.0
Insulin use
36 (33.3%)
Hypertension
75 (69.4%)
Serum HbA1c (%)
7.22 ± 1.15
Systolic blood pressure (mmHg)
134.0 ± 15.6
Serum creatinine (mg/dL)
1.20 ± 0.59
eGFR (mL/min)
67.6 ± 34.0
eGFR estimated glomerular filtration rate, SD standard deviation
Longitudinal Changes in eGFR and Other Systemic Parameters After Intravitreal Anti-VEGF for DME
During the treatment period, a mean of 9.1 ± 3.9 injections (range 4–16 injections) were administered to each patient within the first year, and another 2.6 ± 3.0 (range 0–12 injections) injections were administered during the second year. After treatment, the BCVA improved and the CFT decreased from month 3 to month 24 (P < 0.05 for all time points) (Supplementary Fig. 1). Table 2 shows the longitudinal changes in eGFR during the 2-year follow-up period. After receiving intravitreal anti-VEGF therapy for DME, these patients showed a persistent decline in eGFR over time. At month 24 after the first intravitreal injection, the mean decline in eGFR was 11.8 ± 20.5 mL/min (16.5 ± 26.4%) compared to baseline. The serum creatinine continuously increased, which was in concordance with the persistent decline of eGFR. However, the serum HbA1c and SBP were stable during the treatment period (Supplementary Table 2).
Table 2
Changes in estimated glomerular filtration rate at 3, 6, 12, 18, and 24 months after intravitreal injection of anti-VEGF
Changes in eGFR
Mean ± SD (mL/min)
Percentage
P value
Month 3
−4.2 ± 12.6
−5.5 ± 16.6%
0.003
Month 6
−5.6 ± 14.5
−8.1 ± 22.8%
< 0.001
Month 12
−7.1 ± 15.5
−10.4 ± 23.2%
< 0.001
Month 18
−9.7 ± 17.5
−14.2 ± 24.4%
< 0.001
Month 24
−11.8 ± 20.5
−16.5 ± 26.4%
< 0.001
eGFR estimated glomerular filtration rate, SD standard deviation
Longitudinal Changes in eGFR in Different Baseline eGFR Groups
Figure 1 shows the trend in eGFR changes in the different baseline eGFR groups. The eGFR in the 61–90 mL/min group was rather steady and had the smallest decline (4.3 ± 20.0%) among all five groups at month 24. On the contrary, the groups with eGFR > 120 mL/min and 16–30 mL/min had the most significant eGFR decline (18.5 ± 11.9% and 14.7 ± 24.5%, respectively) after three loading injections of anti-VEGF at month 3, and the extent of decline increased to 32.0 ± 20.6% and 37.4 ± 37.9%, respectively, at month 24, which were significantly higher than the 61–90 mL/min group (P = 0.004 and 0.0005, respectively) (Table 3).
Fig. 1
Trends in estimated glomerular filtration rate (eGFR) decline (in percentages) in different baseline eGFR groups (> 120 mL/min, 91–120 mL/min, 61–90 mL/min, 31–60 mL/min, and 16–30 mL/min)
Table 3
Comparison of mean changes in estimated glomerular filtration rate (eGFR) in percentage at month 24 in different baseline eGFR groups (> 120 mL/min, 91–120 mL/min, 61–90 mL/min, 31–60 mL/min, and 16–30 mL/min)
Baseline eGFR (mL/min)
Change in eGFR in percentage
P value
> 120
−32.0 ± 20.6%
0.004
91–120
−19.1 ± 18.7%
0.086
61–90
−4.3 ± 19.7%
(Reference)
31–60
−15.1 ± 28.4%
0.092
16–30
−37.4 ± 30.9%
0.0005
eGFR estimated glomerular filtration rate
×
Longitudinal Changes in eGFR in Different Groups by Age, Sex, and Anti-VEGF Drug
Figure 2A shows the longitudinal eGFR changes in the older group (age 65 or older) and the younger group (age less than 65). No significant differences were noted between the two groups at any time point (all Ps > 0.05). Figure 2B shows the longitudinal eGFR changes between female and male groups, and no significant differences were noted between the two groups at any time point (all Ps > 0.05). Figure 2C shows the longitudinal changes in eGFR in patients receiving ranibizumab and those receiving aflibercept. No significant differences were noted between the two groups at any time point (all Ps > 0.05 for all).
Fig. 2
The trends in estimated glomerular filtration rate (eGFR) decline (in percentages) in different groups by A age, B sex, and C anti-vascular endothelial growth factor drug
×
Factors Associated with Change in eGFR at Month 24
Table 4 shows the factors associated with eGFR change in percentages at month 24 by multiple linear regression analysis. Similar to the previous statement, patients with a baseline eGFR of > 120 mL/min or between 15 and 30 mL/min had a much greater decline in eGFR at month 24 than those with a baseline eGFR between 61 and 90 mL/min (P = 0.004 and P < 0.001, respectively). Duration of diabetes, insulin use, HbA1c, SBP, number of injections, and injection drug type were not correlated with eGFR change at month 24 (P > 0.05).
Table 4
Factors associated with change in estimated glomerular filtration rate in percentage at month 24 by multiple linear regression analysis
Renal Replacement Therapy After Intravitreal Anti-VEGF Treatment
During the 2-year follow-up period, one out of 52 patients (1.9%) receiving ranibizumab and five out of 56 patients (8.9%) receiving aflibercept started hemodialysis or peritoneal dialysis (P = 0.21 by Fisher exact test). None of the enrolled patients had undergone hemofiltration or renal transplantation. Table 3 shows the risk factors for renal replacement therapy after anti-VEGF therapy for DME by multiple Cox regression analysis. Baseline eGFR was the only significant risk factor (hazard ratio = 0.910 per increase of 1 in eGFR, P = 0.005). Duration of diabetes, insulin use, HbA1c, SBP, number of injections, and type of drug injection were not correlated (P > 0.05) (Table 5).
Table 5
Risk factors for dialysis after intravitreal anti-vascular endothelial growth factor for diabetic macular edema by multiple Cox regression analysis
Ranibizumab and aflibercept have been approved by the U.S. Food and Drug Administration (FDA) for many years as intravitreal drugs for the treatment of DME. According to the data from clinical trials including RISE/RIDE and VIVID/VISTA, no significant adverse events of renal diseases were noted after IVR or IVA injections [21, 22]. A post hoc analysis from DRCR.net Protocol T revealed changes in the urinary albumin–creatinine ratio after intravitreal anti-VEGF treatment for DME [23]. However, no corresponding data regarding long-term changes in eGFR after such treatment have been reported in clinical trials. In this study, we found that after IVR or IVA treatment for DME, the eGFR decreased during the 2-year treatment period. The decline was most obvious in patients with a baseline eGFR of > 120 mL/min or 16–30 mL/min. Regression analysis revealed that the baseline eGFR was the only significant factor for retinal replacement therapy after intravitreal anti-VEGF treatment. To our knowledge, this is the first study to reveal long-term eGFR changes after intravitreal anti-VEGF treatment for DME.
One study in diabetic patients reported an average decline in eGFR per year of 0.3%, 1.5%, and 5.7% for those without albuminuria, with microalbuminuria, and with macroalbuminuria, respectively [24]. In the present study, the mean eGFR decline during the first year was 10.4% in the study cohort, which was much larger than the previously reported data for diabetic patients. The mean duration of diabetes in the previous study (3.4 ± 5.8 years) was much shorter than that in the present study (16.6 ± 9.0 years). Although our study results showed that the duration of diabetes was not associated with eGFR decline after intravitreal anti-VEGF, we still cannot compare the study results of these two studies directly. However, this finding implies that IVR or IVA for DME may be related to eGFR decline. VEGF is important for protection of the glomerular filtration barrier, and the blockade of VEGF signaling results in proteinuria and renal toxic events [25]. The relationship between systemic VEGF and diabetic nephropathy has been demonstrated in previous studies, which showed that systemic VEGF inhibition causes proteinuria and the progression of diabetic nephropathy [26]. The doses of systemic anti-VEGF used for organic cancers were much higher than those used for intravitreal injection, so the concentration of anti-VEGF detected in the blood circulation should be even higher when administered systemically than that with intravitreal administration. On the other hand, previous studies have also revealed that intravitreal anti-VEGF may be related to deterioration of renal function and proteinuria [27]. Different types of nephropathy have been reported, including minimal change disease, thrombotic microangiopathy, focal and segmental glomerulosclerosis, acute interstitial nephritis, and the progression of chronic kidney disease [28]. However, causal relationships remain inconclusive. In the present study, we recruited DME patients receiving IVR or IVA because these patients were also at high risk for diabetic nephropathy.
Anzeige
After intravitreal injections, different anti-VEGF agents may enter the systemic circulation in different ways. According to the original data from FDA, intravitreal injections of ranibizumab would lead to a serum level of ∼0.05 nmol/L [29] and ∼0.2 nmol/L for aflibercept [30]. Such serum levels are 200-fold lower than the minimum concentration needed to “maximally inhibit systemic VEGF” and that are thought to be safe. However, Avery et al. [12, 13] showed that bevacizumab, ranibizumab, and aflibercept could all be detected in the systemic bloodstream after intravitreal injection, but only ranibizumab was cleared very quickly. Bevacizumab and aflibercept showed greater systemic exposure, with delayed clearance from the bloodstream. For intravitreal injections of 2 mg of aflibercept, the maximum serum level of aflibercept within 1–3 days after injection was 0.309 nmol/L, which was much higher than the IC50 of aflibercept for systemic VEGF inhibition for several weeks (up to 30 days) [12, 13]. As for ranibizumab, its post-injection serum level was similar to the IC50 of ranibizumab for systemic VEGF inhibition initially, but then quickly declined to below the IC50 within days [12, 13]. One randomized controlled trial also confirmed that aflibercept but not ranibizumab could inhibit systemic VEGF for up to 4 weeks after intravitreal injection [31]. However, in the present study, we found no significant differences in the effects of aflibercept and ranibizumab on changes in renal function. Although the proportion of patients receiving dialysis was higher in the aflibercept group (8.9%) than in the ranibizumab group (1.9%), the difference was not significant (P = 0.21). Another randomized controlled trial showed that for patients receiving long-term intravitreal anti-VEGF treatment for DME, decreases in plasma-free VEGF levels were greater after treatment with aflibercept than with ranibizumab at 4 weeks, while this difference was not significant at 52 weeks [32]. Moreover, after multiple intravitreal injections, the serum levels of ranibizumab and aflibercept were both detectable (in some cases near the IC50) for up to 3 months, although the levels were higher in aflibercept than in ranibizumab [12, 13, 33]. This suggests that detectable serum drug levels, in some aspects, might influence renal function for both aflibercept and ranibizumab. We recommend cautious monitoring for changes in renal function for patients with poor renal function when receiving aflibercept or ranibizumab.
Interestingly, patients with extremely high (> 120 mL/min) or low (16–30 mL/min) baseline eGFR experienced the greatest eGFR decline after intravitreal anti-VEGF treatment for DME. It is reasonable that those who already have very poor renal function are prone to further renal function decline due to anti-VEGF-related renal injury. As for those with high eGFR at baseline, some previous studies found that patients with type 2 diabetes who had high eGFR (≥ 120 mL/min/1.73 m2) were more likely to experience a subsequent rapid decline in eGFR during follow-up [34], which was compatible with our results. However, these patients had rather well-preserved renal function, so the effect of intravitreal anti-VEGF therapy should be less concerning. For those with poor baseline renal function, a further decline in eGFR would result in the need for renal replacement therapy. Therefore, close monitoring of renal function may be necessary if these patients require long-term intravitreal anti-VEGF treatment.
The major limitation of this study is its retrospective nature. Since eGFR was not routinely checked for patients receiving intravitreal anti-VEGF for DME, there may have been selection bias because we enrolled only patients with eGFR data before and after their initial anti-VEGF treatments. Another limitation is that only a few patients received renal replacement therapy. Also, there was no control group in this study. However, this is the first study to investigate the long-term effects of intravitreal anti-VEGF on renal function.
Conclusions
In conclusion, we found that for patients receiving intravitreal anti-VEGF therapy for DME, there was a persistent decline in eGFR during the 2-year treatment course. Among the different groups of baseline eGFR, the > 120 mL/min and 16–30 mL/min groups had the greatest eGFR decline, while the eGFR in the 61–90 mL/min group was more steady during the course and had the smallest decline after the 2-year treatment. Baseline eGFR was the only factor correlating with renal replacement therapy after intravitreal anti-VEGF treatment for DME. Patients with poor renal function should be cautiously monitored for changes in renal function after receiving intravitreal anti-VEGF therapy.
Anzeige
Acknowledgements
Author Contribution
Yi-Chung Fang: conduct of study, data collection and analysis, drafting the manuscript; Ivan Pochou Lai: data collection and analysis; Tso-Ting Lai: data collection and interpretation; Ta-Ching Chen: data collection and interpretation; Chang-Hao Yang: data collection and interpretation; Tzyy-Chang Ho: data collection and interpretation; Chung-May Yang: data collection and interpretation; Yi-Ting Hsieh: design of study, data collection and interpretation; critical revision of the manuscript.
Funding
No funding or sponsorship was received for this study. The journal’s Rapid Service fee was funded by National Taiwan University Hospital.
Editorial Assistance
The Editage Taiwan Inc. provided the editorial assistance, and National Taiwan University Hospital provided the funding for this assistance.
Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Anzeige
Ethical Approval
The study was approved by the Research Ethics Committee of the National Taiwan University Hospital (No. 202005058RINA). The need for informed consent was waived because of the retrospective nature of the study. This study adhered to the tenets of the Declaration of Helsinki.
Conflict of Interest
Yi-Chung Fang, Ivan Pochou Lai, Tzyy-Chang Ho and Chung-May Yang declare that they have no conflict of interest. Tso-Ting Lai, Ta-Ching Chen, Chang-Hao Yang and Yi-Ting Hsieh declared speaker fees from Novartis Taiwan and Bayer Taiwan.
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.
Eine perioperative Therapie mit Nivolumab reduziert das Risiko für Rezidive und Todesfälle bei operablem NSCLC im Vergleich zu einer alleinigen neoadjuvanten Chemotherapie um über 40%. Darauf deuten die Resultate der Phase-3-Studie CheckMate 77T.
Immunchemischer Stuhltest positiv, Koloskopie negativ – in solchen Fällen kann die Blutungsquelle auch weiter proximal sitzen. Ein Forschungsteam hat nachgesehen, wie häufig und in welchen Lokalisationen das der Fall ist.
Möglicherweise hängt es von der Art der Diabetesmedikamente ab, wie hoch das Risiko der Betroffenen ist, dass sich sehkraftgefährdende Komplikationen verschlimmern.
Update Innere Medizin
Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.
