Renal thrombotic microangiopathy and nephrotic proteinuria induced by intravitreal injection of aflibercept for diabetic macular edema.

BACKGROUND: Vascular endothelial growth factor inhibitors (VEGFIs) are used to treat malignant neoplasms and ocular diseases by inhibiting angiogenesis. Systemic use of VEGFIs has various side effects, including hypertension, proteinuria, and thrombotic microangiopathy, but adverse events due to intravitreal injection of VEGFIs have not been fully clarified. Although age-related macular degeneration was initially the most common target of intravitreal injection of VEGFIs, it has also been applied sporadically for diabetic macular edema in recent years. Proteinuria following intravitreal injection of VEGFIs would be reversible. In patients with diabetes mellitus (DM), however, it would be difficult to determine whether kidney damage arises from the clinical course of DM or from intravitreal injection of VEGFIs for diabetic macular edema. CASE PRESENTATION: A 55-year-old woman with a 20-year history of type 2 DM began intravitreal injection of VEGFI (aflibercept, 2 mg every 4 weeks) for treatment of diabetic macular edema 2 years previously. She presented with leg edema, hypertension, and nephrotic-range proteinuria 14 months after the first injection. Histological examination of renal biopsy specimens revealed diabetic nephropathy with renal thrombotic microangiopathy probably associated with intravitreal injection of VEGFI. The patient's nephrotic syndrome completely improved at 6 months after simply discontinuing aflibercept. CONCLUSIONS: This is a precious report of pathologically investigated renal thrombotic microangiopathy leading to nephrotic syndrome due to intravitreal injection of aflibercept for diabetic macular edema in a patient with type 2 DM. Renal function and proteinuria should be monitored in diabetic patients who receive intravitreal injection of a VEGFI. If kidney damage develops independent of the clinical course of DM during intravitreal injection of a VEGFI, renal biopsy should be performed and intravitreal VEGFI injection discontinued.

Utility of urinary albumin excretion as an index for stratifying the residual cardiovascular risk in patients undergoing antihypertensive agents treatment.

BACKGROUND: Patients treated with antihypertensive medication, even those with well controlled blood pressure (BP), are at higher risk for the development of atherosclerotic cardiovascular disease (ASCVD) in comparison to nonhypertensive individuals with optimal risk levels. We hypothesized that this residual risk could be stratified based on urinary albumin excretion (UAE). METHODS: A total of 13 082 middle-aged and older individuals with SBP/DBP of less than 160/100 mmHg and urinary albumin-to-creatinine ratios (UACRs) of less than 300 mg/g, and who were free from ASCVD events, were followed to investigate the incidence of ASCVD. The baseline BP was classified into four categories: normal BP (BP1), high normal BP (BP2), elevated BP (BP3), and grade 1 hypertension (BP4) based on the 2019 Japanese Society of Hypertension guidelines. RESULTS: After an average 10.6 ±â€Š2.6 years of follow-up, the multivariable hazard ratio for the development of ASCVD (n = 994) was already increased in medicated hypertensive patients with BP1 in comparison with untreated individuals with BP1; however, among medicated hypertensive patients, this risk was separated between the UAE groups, which were classified according to the median UACR (male, 15.4 mg/g; female, 19.0 mg/g). In medicated hypertensive patients with any category of BP1-BP3, the adjusted risk of the development of ASCVD in those with lower and higher UACRs was comparable to that observed in untreated individuals in the BP1 and BP4 categories, respectively. CONCLUSION: In medicated patients with well controlled hypertension, UAE is useful for stratifying the residual risk of developing ASCVD in comparison to nonhypertensive individuals with optimal risk levels.

Additional prognostic value of electrocardiographic left ventricular hypertrophy in traditional cardiovascular risk assessments in chronic kidney disease.

BACKGROUND: Left ventricular hypertrophy (LVH) is a common predictor of the cardiovascular prognosis in chronic kidney disease (CKD). However, whether or not electrocardiography-derived LVH (ECG-LVH) has prognostic value in patients with various degrees of CKD and improves the cardiovascular risk stratification based on traditional risk factors remains unclear. METHODS: A total of 7206 participants at least 40 years of age who were free from cardiovascular events in a general population were followed for the incidence of cardiovascular events. CKD was confirmed by either the presence of a reduced estimated glomerular filtration rate (eGFR) (<60 ml/min per 1.73 m) or albuminuria, defined as a urinary albumin-to-creatinine ratio (UACR) of at least 30 mg/g Cr. RESULTS: A total of 1886 (26.2%) had CKD, of which 1471 (78.0%) had a preserved eGFR (CKD stage 1-2). After an average 11.3 years of follow-up, the adjusted hazard ratio for the incidence of cardiovascular events significantly increased for ECG-LVH according to the Sokolow--Lyon voltage, Cornell voltage, or Cornell voltage product among participants with CKD (hazard ratio 1.47, P = 0.002), in contrast to those without CKD (hazard ratio 1.15, P = 0.210). The inclusion of any ECG-LVH parameters improved the accuracy of reclassification in any risk prediction model based on the eGFR, UACR, or Framingham 10-year risk score in the CKD participants (net reclassification improvement = 0.13-0.32, all P values <0.040). CONCLUSION: In patients with CKD stage 1-5, ECG-LVH is useful for predicting the risk of future cardiovascular events and adds prognostic information to traditional cardiovascular risk assessments.