Higher Glomerular Filtration Rate Research Articles

Lean body mass in living kidney donors impacts postoperative renal function

PurposeA living donor kidney transplant is the optimal treatment for chronic renal impairment. Our objective is to assess if lean skeletal muscle mass and donor factors such as body mass index, hypertension, and age impact on renal function following donor nephrectomy.MethodsPotential donors undergo CT angiography as part of their work-up in our institution. Using dedicated software (Horos®), standardized skeletal muscle area measured at the L3 vertebrae was calculated. When corrected for height, skeletal muscle index can be derived. Skeletal muscle mass index below predefined levels was classified as sarcopenic. The correlation of CT-derived skeletal muscle index and postoperative renal function at 12 months was assessed. Co-variables including donor gender, age, body mass index (BMI), and presence of pre-op hypertension were also assessed for their impact on postoperative renal function.Results275 patients who underwent living donor nephrectomy over 10 years were included. Baseline pre-donation glomerular filtration rate (GFR) and renal function at one year post-op were similar between genders. 29% (n = 82) of patients met the criteria for CT-derived sarcopenia. Sarcopenic patients were more likely to have a higher GFR at one year post-op (69.3 vs 63.9 mL/min/1.73 m2, p < 0.001). The main factors impacting better renal function at one year were the presence of sarcopenia and younger age at donation.ConclusionWhen selecting donors, this study highlights that patients with low skeletal mass are unlikely to underperform in terms of recovery of their renal function postoperatively at one year when compared to patients with normal muscle mass and should not be a barrier to kidney donation.

Predicting the reversion from mild cognitive impairment to normal cognition based on magnetic resonance imaging, clinical, and neuropsychological examinations.

Reversion from mild cognitive impairment (MCI) to normal cognition (NC) is not uncommon and indicates a better cognitive trajectory. This study aims to identify predictors of MCI reversion and develop a predicting model. A total of 391 MCI subjects (mean age=74.3years, female=61%) who had baseline data of magnetic resonance imaging, clinical, and neuropsychological measurements were followed for two years. Multivariate logistic analyses were used to identify the predictors of MCI reversion after adjusting for age and sex. A stepwise backward logistic regression model was used to construct a predictive nomogram for MCI reversion. The nomogram was validated by internal bootstrapping and in an independent cohort. In the training cohort, the 2-year reversion rate was 19.95%. Predictors associated with reversion to NC were higher education level (p=0.004), absence of APOE4 allele (p=0.001), larger brain volume (p<0.005), better neuropsychological measurements performance (p<0.001), higher glomerular filtration rate (p=0.035), and lower mean arterial pressure (p=0.060). The nomogram incorporating five predictors (education, hippocampus volume, the Alzheimer's Disease Assessment Scale-Cognitive score, the Rey Auditory Verbal Learning Test-immediate score, and mean arterial pressure) achieved good C-indexes of 0.892 (95% confidence interval [CI], 0.859-0.926) and 0.806 (95% CI, 0.709-0.902) for the training and validation cohort. Observational duration is relatively short; The predicting model warrant further validation in larger samples. This prediction model could facilitate risk stratification and early management for the MCI population.

Glomerular hyperfiltration as a therapeutic target for CKD.

The global burden of chronic kidney disease (CKD) is high and increasing. Early diagnosis and intervention are key to improve outcomes. Single nephron glomerular hyperfiltration is an early pathophysiologic manifestation of CKD that may result in absolute glomerular hyperfiltration, i.e. a high glomerular filtration rate (GFR) or be associated with normal or low GFR because of nephron loss (relative glomerular hyperfiltration). Even though compensatory glomerular hyperfiltration may contribute to maintain kidney function after loss of kidney mass, the associated increased glomerular capillary pressure and glomerular and podocyte size drive podocyte loss, albuminuria and proximal tubular overload, contributing to CKD progression. In this regard, all kidney protective drugs in clinical use so far, from renin-angiotensin system blockers to mineralocorticoid receptor blockers to sodium-glucose cotransporter-2 inhibitors to tolvaptan, induced an early dip in glomerular filtration that is thought to represent reversal of hyperfiltration. As glomerular hyperfiltration may be present early in the course of kidney disease, its recognition may provide an effective intervention window that may predates current criteria based on high albuminuria or loss of GFR. Nevertheless, there is no diagnostic method with high sensitivity and specificity to identify single nephron glomerular hyperfiltration, except when it leads to obvious absolute glomerular hyperfiltration, as observed in the early stages of diabetic kidney disease when nephron mass is still preserved. We now review the concept of glomerular hyperfiltration as an indicator of CKD risk, including definitions, challenges in diagnosis and evaluation, underlying pathophysiological mechanisms, potential therapeutic approaches and unanswered questions.

Impact of urate-lowering therapy on the course of chronic kidney disease in patients with asymptomatic hyperuricemia: a meta-analysis of randomized controlled trials

The presented study has been carried out to identify the effect of urate-lowering therapy with xanthine oxidase inhibitors on glomerular filtration rate and serum uric acid in patients with asymptomatic hyperuricemia and chronic kidney disease. A systematic review of randomized controlled trials has been conducted; its results based on meta-analysis has been evaluated.&#x0D; A systematic search and selection of publications in Embase, PubMed, Cochrane Library, and eLibrary databases has been performed. The studied drugs were xanthine oxidase inhibitors: allopurinol and febuxostat. The study considered the following parameters such as efficacy endpoints, namely, glomerular filtration rate and serum uric acid after 3–15 months of follow-up. Clinical and methodological heterogeneity of the included randomized controlled trials has been assessed as well as publication bias and risk of systematic error. Synthesis has been performed using bivariate meta-analysis assessing residual statistical heterogeneity.&#x0D; 7 selected randomized controlled trials (1203 patients) have been included in the meta-analysis. This analysis revealed that medication urate-lowering therapy (allopurinol or febuxostat) was associated with higher glomerular filtration rate (+3.0 ml/min/1.73 m2; 95% confidence interval +0.4 to +5.6; p = 0.022) compared with the controls (placebo/no urate-lowering therapy) at 3–15 months of follow-up. Along with this, medication urate-lowering therapy (allopurinol or febuxostat) has been found to result in lower serum uric acid (−3.3 mg/dl; 95% confidence interval −3.8 to −2.8; р 0.001) compared to the controls (placebo / no urate-lowering therapy) at 3–15 months of follow-up.&#x0D; The results of the meta-analysis have demonstrated a positive role of allopurinol and febuxostat in increasing glomerular filtration rate and decreasing serum uric acid in patients with chronic kidney disease and asymptomatic hyperuricemia. The presented data suggest that therapeutic measures aimed at the elimination of asymptomatic hyperuricemia, including the use of xanthine oxidase inhibitors, may be important in slowing the progression of chronic kidney failure and may be additional factors of nephroprotection.

Pre-transplant glomerular hyperfiltration is not a risk factor for increased renal morbidity and mortality in pediatric stem cell transplant patients.

Low glomerular filtration rate (GFR) prior to stem cell transplant (SCT) is associated with increased morbidity and mortality. The implications of abnormally high GFRs, or glomerular hyperfiltration, prior to SCT are unknown. Twenty-two of 74 consecutive pediatric SCT patients over 2years old at a single center were hyperfiltrating prior to SCT, median nuclear medicine GFR 154mL/min/1.73m2 [interquartile range: 146-170]. There was no association between hyperfiltration and any transplant demographics, nor between hyperfiltration and acute kidney injury (p=.8), renal replacement therapy (p=.63), 1-year event-free survival (p=1), or abnormal creatinine-based estimated GFR at a median follow-up of 4.7years (p=.73).

The role of angiotensin converting enzyme (insertion)/(deletion) and angiotensin II type 1 receptor (A1166C) gene polymorphisms in antiproteinuric effect of ACE inhibitors in type 2 diabetic Iraqi patients

The angiotensin converting enzyme (ACE) I\D gene polymorphism influences the blood ACE enzyme activity. Renoprotective effect of ACE inhibitors (ACEIs) varies among patients due to genetic variation, particularly in Renin-Angiotensin-Aldosterone System genes. This study investigates the genetic variations of ACE I\D and AGT1RA1166C gene polymorphisms in the antiproteinuric effect of ACEI therapy in type 2 diabetes mellitus (T2DM) patients. This is a cross-sectional study that included 76 T2DM patients who are ACEI users, divided into two groups: T2DM without diabetic kidney disease (DKD) included 31 patients, and T2DM with DKD included 45 patients. Urine samples were taken for measurement of urine albumin and creatinine, then calculation of albumin-creatinine ratio (ACR). Blood samples were taken for the measurement of serum parameters and also for the extraction of DNA for genetic evaluation of ACEI/D and AGT1RA1166C gene polymorphisms. The results reveal that T2DM patients carrying the ID genotype have significantly lower ACE1 levels compared to DD and II carriers (p = 0.012). When grouping patients according to the ACR, serum ACE1 and angiotensin-converting enzyme 2 (ACE2) levels were higher in DKD compared to normalbuminuric patients, with the only significant difference for ACE2. After subdividing according to ACE I\D genotypes, the ACE2 differences were only significant in DD genotype carriers (p = 0.049) between DKD and normalbuminuric groups. While for AGT1RA1166C polymorphisms, the AC genotype shows non-significantly lower levels for ACE1 and ACE2. After subdividing according to AGT1RA1166C genotypes, ACE2 levels were significantly higher in DKD patients carrying the AA genotype (p = 0.015). Binary logistic regression analysis revealed that both ACE (I\D) and AGT1RA1166C genes are significant predictors of ACE1 levels after controlling age, gender, and DKD state. This study concluded that both genes are predictors of ACE1 levels; in addition, ID genotype carriers and AC genotype carriers had lower ACE1 and ACE2 levels with lower ACR and higher glomerular filtration rate, identifying better ACEIs responses in ID and AC carriers.

Prevalence of proteinuria and its associated factors in hypertensive diabetic patients.

Hypertensive diabetic patients are at increased risk for chronic kidney disease. Proteinuria is an early sign of kidney damage. Limited research is available on proteinuria and on its associated factors in hypertensive patients with diabetes. This study aimed to assess the prevalence of proteinuria and its associated factors in hypertensive diabetic patients. The current retrospective study utilized medical records and hospital computers to collect sociodemographic and medical information about the study patients in two major hospitals in Jordan. Binary regression analysis was used to find the factors that are significantly and independently associated with the presence of proteinuria. Data from 522 hypertensive diabetic patients were investigated. Factors including age (OR=0.691; 95% CI: 0.930-0.994; p<0.01), high-density lipoprotein level (OR=0.450; 95% CI: 0.211-0.960; p<0.05), and higher glomerular filtration rate (OR=0.964; 95% CI: 0.950-0.977; p<0.01) were associated with proteinuria among the study patients. In contrast to metformin (OR=0.237; 95% CI: 0.098-0.572; p<0.01), patients who received insulin (OR=1.992; 95% CI: 1.136-3.492; p<0.05), thiazide diuretics (OR=1.848; 95% CI: 1.108-3.083; p<0.05), calcium channel blockers (OR=1.833, 95% CI: 1.110-3.028, p<0.05), or beta-blockers (BBs) (OR=2.199, 95% CI: 1.257-3.848, p<0.01) had a higher likelihood of having proteinuria. For preserving kidney function, it is deemed necessary to perform regular checkups for proteinuria among hypertensive diabetic patients, particularly in young patients, patients with low levels of high-density lipoprotein, and those with a lower glomerular filtration rate.

Insulin Secretion, Sensitivity, and Kidney Function in Young Individuals With Type 2 Diabetes.

β-Cell dysfunction and insulin resistance magnify the risk of kidney injury in type 2 diabetes. The relationship between these factors and intraglomerular hemodynamics and kidney oxygen availability in youth with type 2 diabetes remains incompletely explored. Fifty youth with type 2 diabetes (mean age ± SD 16 ± 2 years; diabetes duration 2.3 ± 1.8 years; 60% female; median HbA1c 6.4% [25th, 75th percentiles 5.9, 7.6%]; BMI 36.4 ± 7.4 kg/m2; urine albumin-to-creatinine ratio [UACR] 10.3 [5.9, 58.0] mg/g) 21 control participants with obesity (OCs; age 16 ± 2 years; 29% female; BMI 37.6 ± 7.4 kg/m2), and 20 control participants in the normal weight category (NWCs; age 17 ± 3 years; 70% female; BMI 22.5 ± 3.6 kg/m2) underwent iohexol and p-aminohippurate clearance to assess glomerular filtration rate (GFR) and renal plasma flow, kidney MRI for oxygenation, hyperglycemic clamp for insulin secretion (acute C-peptide response to glucose [ACPRg]) and disposition index (DI; ×103 mg/kg lean/min), and DXA for body composition. Youth with type 2 diabetes exhibited lower DI (0.6 [0.0, 1.6] vs. 3.8 [2.4, 4.5] × 103 mg/kg lean/min; P < 0.0001) and ACPRg (0.6 [0.3, 1.4] vs. 5.3 [4.3, 6.9] nmol/L; P < 0.001) and higher UACR (10.3 [5.9, 58.0] vs. 5.3 [3.4, 14.3] mg/g; P = 0.003) and intraglomerular pressure (77.8 ± 11.5 vs. 64.8 ± 5.0 mmHg; P < 0.001) compared with OCs. Youth with type 2 diabetes and OCs had higher GFR and kidney oxygen availability (relative hyperoxia) than NWCs. DI was associated inversely with intraglomerular pressure and kidney hyperoxia. Youth with type 2 diabetes demonstrated severe β-cell dysfunction that was associated with intraglomerular hypertension and kidney hyperoxia. Similar but attenuated findings were found in OCs.

Patient-specific risk factors for reintervention following primary endovascular treatment of iliac artery disease

ObjectivePredictive models for reintervention may guide clinicians to optimize selection, education, and follow-up of patients undergoing endovascular iliac revascularization. Although the impact of lesion- and device-related characteristics on iliac restenosis and reintervention risk is well-defined, data on patient-specific risk factors are scarce and conflicting. This study aimed to explore the value of patient-related factors in predicting the need for clinically driven target-vessel revascularization (CD-TVR) in patients undergoing primary endovascular treatment of iliac artery disease. MethodsConsecutively enrolled patients undergoing endovascular revascularization for symptomatic iliac artery disease at a tertiary vascular referral center between January 2008 and June 2020 were retrospectively analyzed. Primary and secondary outcomes were CD-TVR occurrence within 24 months and time to CD-TVR, respectively. Patients who died or did not require CD-TVR within 24 months were censored at the date of death or at 730 days, respectively. Multiple imputation was used to account for missing data in primary analyses. ResultsA total of 1538 iliac interventions were performed in 1113 patients (26% females; 68 years). CD-TVR occurred in 108 limbs (74 patients; 7.0%) with a median time to CD-TVR of 246 days. On multivariable analysis, increasing age was associated with lower likelihood of CD-TVR (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.50-0.83; P = .001) and decreased risk of CD-TVR at any given time (hazard ratio [HR], 0.66; 95% CI, 0.52-0.84; P = .001). Similarly, a lower likelihood of CD-TVR (OR, 0.75; 95% CI, 0.59-0.95; P = .017) and decreased risk of CD-TVR at any given time (HR, 0.73; 95% CI, 0.58-0.93; P = .009) were observed with higher glomerular filtration rates. Lastly, revascularization of common vs external iliac artery disease was associated with lower likelihood of CD-TVR (OR, 0.48; 95% CI, 0.24-0.93; P = .030) and decreased risk of CD-TVR at any given time (HR, 0.48; 95% CI, 0.25-0.92; P = .027). No associations were observed between traditional cardiovascular risk factors (sex, hypertension, higher low-density lipoprotein cholesterol, higher hemoglobin A1c, smoking) and CD-TVR. ConclusionsIn this retrospective cohort study, younger age, impaired kidney function, and external iliac artery disease were associated with CD-TVR. Traditional markers of cardiovascular risk were not seen to predict reintervention.

Characterising diabetes in Kazakhstan: a cluster analysis

Abstract Background Diabetes is a global pandemic, affecting 537 million adults worldwide in 2021. Diabetes is much more complex than the classification into type 1 diabetes and type 2 diabetes suggests. We aimed to identify homogeneous groups of patients with diabetes based on routinely collected measurements using unsupervised, data-driven cluster analysis. Methods We analyzed the data from Electronic Medical Records of 558 patients with newly diagnosed diabetes from 4 outpatient clinics in Astana. We performed a k-means cluster analysis of 9 routinely measured variables using the KMeans function (iterations=3 million) from the Scikit-Learn Python library. Results Cluster 1, consisting of 176 (31,5%) patients, was defined by late-onset diabetes, relatively low blood pressure (BP) and body mass index (BMI), moderate metabolic derangements, and comparably low glomerular filtration rate (GFR). The 83 (14,9%) patients in cluster 2 were characterized by a late manifestation of diabetes, high BP and BMI, relatively poor glycemic control, moderate dyslipidemia, and comparably low GFR. Cluster 3, including 98 (17,6%) patients, was represented by a low age at onset, comparably low BP and BMI, moderately poor glycemic and lipid controls, and high GFR. The 110 (19,7%) patients in cluster 4 had late-onset diabetes, high BP and BMI, subcompensated diabetes, poor lipid control, and relatively low GFR. Cluster 5, which involved 91 (16,3%) patients, was characterized by comparably low BP and BMI, poor glycemic control, modest dyslipidemia, and high GFR. Conclusions We intend to continue the project for further conducting a prospective study with dynamic monitoring of study participants, tracking specific patterns in the development of diabetic complications in each cluster. The results of this work will contribute to the development of a model for identifying patients with an initially predictable course of diabetes and a high risk of its complications at the time of diagnosis. Key messages • We identified five clusters of patients with diabetes with clinically significant characteristics in each cluster. • Identification of subgroups of patients with an initially predictable course can be useful for recognizing those at highest risk of complications and applying personalized treatment strategies.

Antihormonal-Treatment Status Affects 68Ga-PSMA-HBED-CC PET Biodistribution in Patients with Prostate Cancer.

Androgen deprivation therapy (ADT) is known to influence the prostate-specific membrane antigen (PSMA) expression of prostate cancer, potentially complicating the interpretation of PSMA ligand PET findings and affecting PSMA radioligand therapy. However, the impact of ADT on PSMA ligand biodistribution in nontumorous organs is not well understood. Methods: Men (n = 112) with histologically proven prostate cancer who underwent 68Ga-PSMA-HBED-CC (68Ga-PSMA-11) PET/CT between November 2015 and July 2021 at the Medical University Vienna with known ADT status were retrospectively recruited. Fifty-six patients were on gonadotropin-releasing hormone-interfering ADT at the time of imaging (ADT group), whereas 56 patients with no history of ADT served as a control group. Physiologically PSMA-expressing organs (salivary glands, kidneys, liver, and spleen) were delineated, and their uptake was compared according to their data distributions. Multivariate regression analysis assessed the relationship between renal, hepatic, splenic, and salivary gland uptake and the explanatory variables metabolic tumor volume, glomerular filtration rate, and ADT status. Results: ADT was associated with lower levels of PSMA uptake in the kidneys (SUVmean: Δ[ADT - control] = -7.89; 95% CI, -10.73 to -5.04; P < 0.001), liver (SUVpeak: Δ[ADT - control] = -2.3; 95% CI, -5.72 to -0.93; P = 0.003), spleen (SUVpeak: Δ[ADT - control] = -1.27; 95% CI, -3.61 to -0.16; P = 0.033), and salivary glands (SUVmean: Δ[ADT - control] = -1.04; 95% CI, -2.48 to -0.13; P = 0.027). In a multivariate analysis, ADT was found to be associated with lower renal (SUVmean: β = -7.95; 95% CI, -11.06 to -4.84; P < 0.0001), hepatic (SUVpeak: β = -7.85; 95% CI, -11.78 to -3.91; P < 0.0001), splenic (SUVpeak: β = -5.83; 95% CI, -9.95 to -1.7; P = 0.006), and salivary gland (SUVmean: β = -1.47; 95% CI, -2.76 to -0.17; P = 0.027) uptake. A higher glomerular filtration rate was associated with a higher renal SUVmean (β = 0.16; 95% CI, 0.05 to 0.26; P = 0.0034). Conclusion: These findings suggest that ADT systemically modulates PSMA expression, which may have implications for treatment-optimizing and side-effect-minimizing strategies for PSMA radioligand therapies, particularly those using more potent 225Ac-labeled PSMA conjugates.

The Number and Size of Individual Kidney Medullary Pyramids is Associated with Clinical Characteristics, Kidney Biopsy Findings, and CKD Outcomes among Kidney Donors.

The kidney is a lobulated organ, but little is known regarding the clinical importance of the number and size of individual kidney lobes. After applying a previously validated algorithm to segment cortex and medulla, a deep-learning algorithm was developed and validated to segment and count individual medullary pyramids on contrast-enhanced computed tomography (CT) images of living kidney donors prior to donation. The association of cortex volume, medullary volume, number of pyramids, and mean pyramid volume with concurrent clinical characteristics (kidney function and chronic kidney disease risk factors), kidney biopsy morphology (nephron number, glomerular volume, and nephrosclerosis), and short- and long-term glomerular filtration rate (GFR) <60 or <45 ml/min/1.73m2 was assessed. Among 2,876 living kidney donors, 1,132 had short-term follow-up at a median of 3.8 months and 638 had long-term follow-up at a median of 10.0 years. Larger cortical volume was associated with young age, male, larger body size, higher GFR, albuminuria, more nephrons, larger glomeruli, less nephrosclerosis, and lower risk of low GFR at follow-up. Larger pyramids were associated with older age, female, larger body size, higher GFR, more nephrons, larger glomerular volume, more nephrosclerosis, and higher risk of low GFR at follow-up. More pyramids were associated with younger age, male, greater height, no hypertension, higher GFR, lower uric acid, more nephrons, less nephrosclerosis, and a lower risk of low GFR at follow-up. Cortical volume and medullary pyramid volume and count reflect underlying variation in nephron number and nephron size, as well as merging of pyramids due to age-related nephrosclerosis, with loss of detectable cortical columns separating pyramids.

Outcomes of percutaneous transluminal renal angioplasty for pediatric renovascular hypertension: a 12-year retrospective single-center experience.

Renovascular disease underlies 5-10% of all childhood hypertension. We evaluated the long-term outcomes of percutaneous transluminal renal angioplasty (PTRA) for pediatric renovascular hypertension (RVH). Data from 37 children with RVH who underwent PTRA of 45 lesions at our center from January 2010 to January 2022 were retrospectively evaluated. Postoperative blood pressure (BP), glomerular filtration rate (GFR), affected kidney size, restenosis, and complications were analyzed. Mean age, weight, and height of patients at first PTRA was 11.51±4.57 (range, 3-17) years, 45.37±22.29 (range, 13.40-106.00) kg, and 1.46±0.26 (range, 0.92-1.85) m, respectively. Technical success was achieved in 33 of 37 (89.2%) patients and 40 of 45 (88.9%) lesions, without surgery-related complications. At a median of 7.5 (range, 3-14) months, restenosis occurred in 6 (16.7%) patients and 7 (16.3%) lesions (all ostial and 6 with a length >15 mm), yielding a clinical beneficial rate from first PTRA of 83.3%. At 18- and 20-month follow-up the mean kidney length (29 kidneys) increased from 8.89±1.55 to 9.79±1.51 cm (P<0.001) and mean GFR (34 kidneys) from 32.28±19.22 to 41.24±13.24 mL/min (P<0.001). In this retrospective analysis, PTRA for the treatment of pediatric RVH can achieve satisfactory results. Angioplasty was associated with improved BP control and long-term preservation of renal function, as reflected by an increase in affected kidney size and a higher GFR.

Does HbA1c Level or Glomerular Filtration Rate Affect the Clinical Response to Endothelial Growth Factor Therapy (Ranibizumab or Aflibercept) in Diabetic Macular Edema? A Real-Life Experience.

Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for diabetic macular edema (DME). We investigated the effect of initial glycosylated hemoglobin (HbA1c) level and glomerular filtration rate (GFR) on treatment outcomes in patients with DME receiving anti-VEGF injections in routine clinical practice. A retrospective analysis of data from the prospective, multi-center, observational Fight Retinal Blindness! registry was performed. A total of 178 eyes with DME treated with anti-VEGF agents (ranibizumab or aflibercept) from 1 January 2010 to 31 March 2019 were enrolled in the analysis, with the long study period to allow for up to 24months of follow-up. Data for eyes were tracked in the Fight Retinal Blindness! registry, and clinical parameters were collected by using local software. Changes in visual (best-corrected visual acuity [BCVA], in letters) and anatomic outcomes (central subfield thickness [CST], in microns) between subgroups of patients according to baseline HbA1c level (≤ 7% vs. > 7%) and GFR (> vs. ≤ 60ml/min/m2 at 24months were assessed. The multivariate adjusted mean improvement in BCVA at 24months of treatment was + 5.2 and + 6.8 letters in subgroups with baseline HbA1c level ≤ 7% and > 7%, respectively (p = 0.541), and + 6.9 and + 6.4 letters in subgroups with GFR > 60 and < 60ml/min/1.73 m2, respectively (p = 0.852). The multivariate adjusted mean CST reduction was -89.9 and -76.4µm in subgroups with baseline HbA1c level ≤ 7% and > 7%, respectively (p = 0.505), and -85 and -115µm in subgroups with baseline GFR > 60 and ≤ 60ml/min/1.73 m2, respectively (p = 0.130). These results seem to indicate that visual and anatomical improvement in patients receiving intravitreal VEGF inhibitors for DME are independent of baseline HbA1c level and GFR, leading to the conclusion that high HbA1c levels or low GFR should not dictate injection timing in routine clinical practice. This study offers valuable insights for ophthalmologists, enabling a personalized treatment approach and optimizing DME patient outcomes.

Blood pressure changes during tenofovir-based antiretroviral therapy among people living with HIV in Lilongwe, Malawi: results from the prospective LighTen Cohort Study

BackgroundSub-Saharan Africa is one of the regions in the world with the highest numbers of uncontrolled hypertension as well as people living with HIV/AIDS (PLHIV). However, the association between hypertension and antiretroviral therapy is controversial.MethodsParticipant demographics, medical history, laboratory values, WHO clinical stage, current medication, and anthropometric data were recorded at study entry and during study visits at 1, 3, 6 months, and every 6 months thereafter until month 36. Patients who stopped or changed their antiretroviral therapy (tenofovir, lamivudine, efavirenz) were censored on that day. Office blood pressure (BP) was categorized using ≥ 2 measurements on ≥ 2 occasions during the first three visits. Factors associated with systolic and mean BP were analyzed using bivariable and multivariable multilevel linear regression.Results1,288 PLHIV (751 females, 58.3%) could be included and 832 completed the 36 months of observation. Weight gain and a higher BP level at study entry were associated with an increase in BP (p < 0.001), while female sex (p < 0.001), lower body weight at study entry (p < 0.001), and high glomerular filtration rate (p = 0.009) protected against a rise in BP. The rate of uncontrolled BP remained high (73.9% vs. 72.1%) and despite indication treatment, adjustments were realized in a minority of cases (13%).ConclusionAdherence to antihypertensive treatment and weight control should be addressed in patient education programs at centers caring for PLHIV in low-resources settings like Malawi. Together with intensified training of medical staff to overcome provider inertia, improved control rates of hypertension might eventually be achieved.Trial registrationNCT02381275.Graphical abstract

Inflammatory Biomarkers Affecting Survival Prognosis in Patients Receiving Veno-Venous ECMO for Severe COVID-19 Pneumonia.

Severe COVID-19 pneumonia in which mechanical ventilation is unable to achieve adequate gas exchange can be treated with veno-venous ECMO, eliminating the need for aggressive mechanical ventilation which might promote ventilator-induced lung injury and increase mortality. In this retrospective observational study, 18 critically ill COVID-19 patients who were treated using V-V ECMO during an 11-month period in a tertiary COVID-19 hospital were analyzed. Biomarkers of inflammation and clinical features were compared between survivors and non-survivors. Survival rates were compared between patients receiving ECMO and propensity matched mechanically ventilated controls. There were 7 survivors and 11 non-survivors. The survivors were significantly younger, with a higher proportion of females, higher serum procalcitonin at ICU admission, and before initiation of ECMO they had significantly lower Murray scores, PaCO2, WBC counts, serum ferritin levels, and higher glomerular filtration rates. No significant difference in mortality was found between patients treated with ECMO compared to patients treated using conventional lung protective ventilation. Hypercapnia, leukocytosis, reduced glomerular filtration rate, and increased serum ferritin levels prior to initiation of V-V ECMO in patients with severe COVID-19 pneumonia may be early warning signs of reduced chance of survival. Further multicentric studies are needed to confirm these findings.

Durable Anti-SARS-CoV-2 Antibody Response after mRNA-1273 Booster in Peritoneal Dialysis Patients during the Omicron Wave.

Anti-SARS-CoV-2 vaccination of dialysis patients has been proven to be safe and effective to reduce COVID-19-related morbidity and mortality. However, data on the durability of anti-SARS-CoV-2 antibodies post-vaccination in peritoneal dialysis (PD) patients are scarce. In this prospective single-center cohort study we measured anti-SARS-CoV-2 RBD antibodies 3 and 6 months after the 3rd dose of the mRNA-1273 vaccine in 27 adult PD patients and recorded breakthrough infections. Furthermore, in a mixed model analysis, we analyzed potential factors influencing the humoral response following vaccination. Anti-SARS-CoV-2 RBD antibody levels declined from 21,424 BAU/mL at 1 month to 8397 BAU/mL at 3 months and to 5120 BAU/mL at 6 months after the 3rd dose, but remained higher than pre-3rd dose levels (212 BAU/mL). Eight patients (29.6%) were infected with SARS-CoV-2 within six months from the 3rd dose during the Omicron wave. Previous high antibody levels, high glomerular filtration rate (GFR) and low Davies Comorbidity Score were associated with higher anti-SARS-CoV-2 antibody levels after the booster. In conclusion, PD patients exhibited a robust and durable humoral response after a third dose of the mRNA-1273 vaccine. A high GFR and low comorbidity as well as previous high antibody levels predicted a better humoral response to vaccination.

Mortality After the First Hospital Admission for Acute Heart Failure, De Novo Versus Acutely Decompensated Heart Failure With Reduced Ejection Fraction

It is not clear to date whether a first admission in heart failure (HF) marks a worse evolution in patients not previously diagnosed with HF ("de novo HF") than those already diagnosed as outpatients ("acutely decompensated HF"). The aim of the study was to analyze whether survival in patients admitted for de novo HF differs from the survival in those admitted for a first episode of decompensation but with a previous diagnosis of HF. This study includes an analysis of 1,728 patients admitted for decompensated HF during 9years. Readmissions and patients with left ventricular ejection fraction ≥50% were excluded (finally, 524 patients analyzed). We compared de novo HF (n=186) in patients not diagnosed with HF, although their structural heart disease was defined, versus acutely decompensated HF (n=338). The clinical profiles in both groups were similar. The de novo HF group more frequently presented with normal right ventricular function, with less presence of severe tricuspid regurgitation. The probability of survival was low in both groups. Thus, the median life in the de novo HF group was 2.1years and in the acutely decompensated HF group, 3.5years. There was a lower probability of long-term survival in the de novo HF group (p=0.035). The variables associated with mortality were age (p <0.0001), ischemic heart disease (p <0.0001), hypertension (p=0.009), obesity (p=0.025), diabetes (p=0.001), and N-terminal pro-brain natriuretic peptide at admission (p <0.0001). A higher glomerular filtration rate was associated with better survival (p=0.033). De novo HF was associated with a higher mortality than chronic HF with acute decompensation (hazard ratio 1.53, 95% confidence interval 1.03 to 2.27, p=0.036). In conclusion, the first admission for HF decompensation in patients with no previous diagnosis of HF identifies a subgroup of patients with higher long-term mortality.

Clinical Manifestations, Pathological Correlations, Prognostic Factors, and Outcomes of Severe Acute Postinfectious Glomerulonephritis with Rapidly Progressive Glomerulonephritis in Children

Objective: To describe clinical spectrum, as well as biochemical and histological factors that could predict severe presentations and renal outcomes among children with rapidly progressive glomerulonephritis (RPGN) due to postinfectious glomerulonephritis (PIGN). Material and Methods: A retrospective cohort study was conducted at Chiang Mai University Hospital, Thailand between February 2008 and January 2018. Ninety-six pediatric patients with PIGN were recruited. Clinical presentations, disease courses, laboratory data, renal histopathology, treatment, and outcomes were analyzed. Compare clinical manifestation and outcome between the two groups. Results: The median age (interquartile range, IQR) was 11 (8 to 13) years with a male-to-female ratio of 1.8:1. RPGN was identified in 51.04% (49/96 patients). PIGN children with RPGN exhibited a higher prevalence of nephrotic range proteinuria (69.4% versus 53.2%, p=0.04), nephrotic syndrome (46.9% versus 17%, p=0.002), and hypoalbuminemia (81.3% versus 53.8%, p&lt;0.0001) compared with those without RPGN. Multivariate analysis revealed that anuria, and hypoalbuminemia were predicting factors of RPGN [odd ratios 0.07 (95% CI 0.01 to 0.77), p=0.03 and 0.23 (95% CI 0.08 to 0.69), p=0.006, respectively]. Follow-up data were available among 78 patients (81.3%) with a median follow-up time of 762 (256.3 to 1,293) days. Complete remission was identified in all of PIGN without RPGN but only 71.4% in the RPGN group. Kaplan-Meier analysis revealed that patients with RPGN had a longer recovery time of generalized edema at 14 days (95% CI 12 to 15.9) versus 9 days (95% CI 7 to 12), p=0.023; proteinuria at 16 weeks (95% CI 11 to 20.8) versus 8 weeks (95% CI 4.25 to 15.75), p&lt;0.0001; and impaired glomerular filtration rate (GFR) of nine weeks (95% CI 4.8 to 13.2) versus two weeks (95% CI 1 to 8), p=0.003. Subgroup analysis of prognostic factors of PIGN with RPGN revealed that high BMI z-score and kidney replacement therapy (KRT) requirement were associated with poor renal outcomes. Conclusion: Hypoalbuminemia and anuria were predictive factors of RPGN in PIGN. High BMI z-score and low GFR required acute KRT were predictive factors of poor renal outcomes. Keywords: Postinfectious glomerulonephritis; Acute post streptococcal glomerulonephritis; Rapidly progressive glomerulonephritis; Children

Renal Functional Response-Association With Birth Weight and Kidney Volume

Renal functional response (RFR) is the acute increase in glomerular filtration rate (GFR) after a protein load. Low RFR is a marker of single nephron hyperfiltration. Low birth weight (LBW) is associated with reduced number of nephrons, lower kidney function, and smaller kidneys in adults. In the present study, we investigate the associations among LBW, kidney volume, and RFR. We studied adults aged 41 to 52 years born with either LBW (≤2300 g) or normal birth weight (NBW; 3500-4000 g). GFR was measured using plasma clearance of iohexol. A stimulated GFR (sGFR) was measured on a separate day after a protein load of 100 g using a commercially available protein powder, and RFR was calculated as delta GFR. Kidney volume was estimated from magnetic resonance imaging (MRI) images using the ellipsoid formula. A total of 57 women and 48 men participated. The baseline mean ± SD GFR was 118 ± 17 ml/min for men and 98 ± 19 ml/min for women. The overall mean RFR was 8.2 ± 7.4 ml/min, with mean RFR of 8.3 ± 8.0 ml/min and 8.1 ± 6.9 ml/min in men and women, respectively (P= 0.5). No birth-related variables were associated with RFR. Larger kidney volume was associated with higher RFR, 1.9 ml/min per SD higher kidney volume (P= 0.009). Higher GFR per kidney volume was associated with a lower RFR,-3.3ml/min per SD (P< 0.001). Larger kidney size and lower GFR per kidney volume were associated with higher RFR. Birth weight was not shown to associate with RFR in mainly healthy middle-aged men and women.