Baseline Glomerular Filtration Rate Research Articles

Serum matrix metalloproteinase 7 and accelerated glomerular filtration rate decline in a general non-diabetic population.

BackgroundAge-related reduction of glomerular filtration rate (GFR) is a major contributor to the global chronic kidney disease (CKD) epidemic. We investigated whether baseline serum levels of the pro-fibrotic matrix metalloproteinase 2 (MMP2), MMP7 and their inhibitor, tissue inhibitor of metalloproteinase 1 (TIMP1), which mediates fibrosis development in aging animals, were associated with GFR decline in a general non-diabetic population.MethodsIn the Renal Iohexol Clearance Survey, we measured GFR using iohexol clearance in 1627 subjects aged 50–64 years without self-reported diabetes, kidney or cardiovascular disease. After a median of 5.6 years, 1324 had follow-up GFR measurements. Using linear mixed models and logistic regression analyses, we evaluated the association of MMP7, MMP2 and TIMP1 with the mean GFR decline rate, risk of accelerated GFR decline (defined as subjects with the 10% steepest GFR slopes: ≥1.8 mL/min/1.73 m2/year) and incident CKD [GFR <60 mL/min/1.73 m2 and/or urinary albumin to creatinine ratio (ACR) ≥3.0 mg/mmol].ResultsHigher MMP7 levels (per standard deviation increase of MMP7) were associated with steeper GFR decline rates [−0.23 mL/min/1.73 m2/year (95% confidence interval −0.34 to −0.12)] and increased risk of accelerated GFR decline and incident CKD [odds ratios 1.58 (1.30–1.93) and 1.45 (1.05–2.01), respectively, in a model adjusted for age, sex, baseline GFR, ACR and cardiovascular risk factors]. MMP2 and TIMP1 showed no association with GFR decline or incident CKD.ConclusionsThe pro-fibrotic biomarker MMP7, but not MMP2 or TIMP1, is associated with increased risk of accelerated GFR decline and incident CKD in middle-aged persons from the general population.

Bariatric Surgery Improves Renal Function in Patients With Obesity.

BackgroundObesity affects 93.3 million adults in the United States and is a predisposing factor for the development and progression of chronic kidney disease (CKD). The objective of this study is to examine the association between weight loss and renal function in participants undergoing bariatric surgery following a 12-week multidisciplinary, community-based weight loss program.MethodologyThis is a retrospective chart review of participants who voluntarily enrolled in a 12-week multidisciplinary weight loss program prior to bariatric surgery from 2009 to 2018. The primary outcome was to assess the association between weight loss and renal function in participants undergoing bariatric surgery. Secondary outcomes included changes in hemoglobin A1c, lipids, fasting glucose, and blood pressure.ResultsAmong the 55 participants, baseline glomerular filtration rate (GFR) was 49 mL/min/m2, 80% were female, and the average baseline weight was 131 kg. At one-year post-intervention, 69% of patients improved in the CKD stage, with 45% of the participants improving from stage 3A to stage 2. GFR improved to 15 mL/min/1.73m2 (p = 0.025), and there was a negative correlation (rs = -0.3556) between weight and GFR (p = 0.013). Participants with hyperlipidemia had a 12 mL/min/1.73m2 rise in GFR, while participants without the diagnosis at one year had a 24 mL/min/1.73m2 rise in GFR (p = 0.007).ConclusionsThis study demonstrated improved renal function and reduced progression of CKD following a combined lifestyle and surgical intervention, indicating the importance of a comprehensive approach for the management of the chronic disease.

Transcatheter tricuspid valve repair: early experience in the Netherlands.

BackgroundSymptomatic tricuspid regurgitation (TR) is increasingly prevalent and impairs quality of life and survival, despite medical treatment. Transcatheter tricuspid valve repair (TTVR) has recently become available as a treatment option for patients not eligible for tricuspid valve surgery. In this study we describe the early experience with TTVR in the Netherlands.MethodsAll consecutive patients scheduled for TTVR in two tertiary hospitals were included in the current study. Patients were symptomatic and had severe functional TR. TTVR was performed either with the MitraClip (off-label use) or dedicated TriClip delivery system and device. Procedural success was defined as achievement of clip implantation, TR reduction ≥ 1 grade and no need for re-do surgical or transcatheter intervention. Clinical improvement was evaluated after 4 weeks.ResultsTwenty-one patients (median age 78 years, 33% male, 95% New York Heart Association class ≥ 3, 100% history of atrial fibrillation) underwent TTVR. Procedural success was achieved in 16 patients, of whom 15 reported symptomatic improvement (New York Heart Association class 1 or 2). There was no in-hospital mortality and no major complications occurred. Baseline glomerular filtration rate and TR coaptation gap size were associated with procedural success.ConclusionThe current study showed that TTVR seems a promising treatment option for patients with severe functional TR deemed high risk for surgery. Successful TR reduction is most likely in patients with limited coaptation gap size and strongly determines clinical benefit. Adequate patient selection and timing of treatment seem essential for an optimal patient outcome.Supplementary InformationThe online version of this article (10.1007/s12471-021-01613-3) contains supplementary material, which is available to authorized users.

The roles of protein load test in quantitatively evaluating renal function after severe unilateral ureteral obstruction in adult rabbits.

The accuracy of dynamic renal scintigraphy in evaluating the function of hydronephrotic kidneys is controversial. This study sought to investigate the effects of ureteral obstruction on renal function and the role of the protein load test (PLT) in evaluating hydronephrotic kidneys' function. A ureteral obstruction model was generated with New Zealand white rabbits. The baseline glomerular filtration rate (GFR) and the GFR during the PLT were measured by dynamic renal scintigraphy at weeks 6, 9, and 12 after obstruction and the renal reserve GFRs were calculated. The renal GFR differences between different time points and between the PLT and baseline status were compared. (I) Both the baseline GFRs (t=11.287, P=0.000) and the GFRs during the PLTs (t=16.235, P=0.000) of the hydronephrotic kidneys were significantly lower than those of the contralateral kidneys. (II) The baseline GFRs of the obstructed kidneys were not significantly different 6, 9, and 12 weeks after obstruction (F=0.122, P=0.887), but their net reserve GFRs (F=8.419, P=0.004) and relative reserve GFRs (F=3.770, P=0.049) gradually decreased over time. (III) There was no significant correlation between the net reserve GFRs (r=-0.006, P=0.977) or the relative reserve functions (r=-0.022, P=0.920) of the obstructed kidneys and their baseline GFRs. However, there was a significant negative correlation between the net reserve GFRs (r=-0.590, P=0.002) or the relative reserve functions (r=-0.546, P=0.006) of the obstructed kidneys and the duration of obstruction. (IV) The reserve GFRs of the obstructed kidneys were not proportional to their baseline GFRs. The functional changes in hydronephrotic kidneys are not sensitively reflected by baseline GFRs. GFRs during the PLTs and the reserve GFRs play important roles in the early and accurate evaluation of the function of obstructed kidneys.

Impact of Chronic Kidney Disease in Chronic Total Occlusion Management and Clinical Outcomes

BackgroundData on the impact of chronic kidney disease (CKD) on clinical outcomes in chronic total occlusion (CTO) patients is scarce, and the optimal treatment strategy for this population is not well established. This study aims to compare differences in CTO management and long-term clinical outcomes, including all-cause and cardiac mortalities, according to baseline glomerular filtration rate (GFR). MethodsAll patients with at least one CTO diagnosed in our center between 2010 and 2014 were included. Demographic and clinical data were registered. All-cause and cardiac mortalities were assessed during a median follow-up of 4.03 years (IQR 2.6–4.8). Clinical outcomes were compared between patients with CKD (GFR < 60 mL/min/1.73 m2) and without CKD (GFR ≥ 60 mL/min/1.73 m2). ResultsA total of 1248 patients (67.3 ± 10.9 years; 32% CKD) were identified.CKD patients were older and had a higher prevalence of hypertension, type 2 diabetes, peripheral arterial disease, and severe left ventricular dysfunction compared to patients with normal renal function (p < 0.05).Subjects with renal dysfunction were more often treated with MT alone, compared to patients without CKD (63% vs 45%; p < 0.001), who were more likely to undergo PCI or surgery. During follow-up, 386 patients [31%] died. CKD patients had a higher rate of all-cause and cardiac mortalities compared to patients without CKD (p < 0.001). The independent predictors for all-cause mortality were age, GFR < 60 mL/min/1.73 m2, Syntax Score I, and successful revascularization of the CTO (CABG or PCI-CTO). Among patients with CKD, advanced age, eGFR <30 mL/min/1.73 m2, and CTO successful revascularization were predictors of all-cause mortality. ConclusionsPatients with CKD were more often treated with MT alone. At long-term follow-up, revascularization of the CTO is associated with lower all-cause and cardiac mortalities in this population.

Systemic Immune-Inflammation Index Is a Predictor of Contrast-Induced Nephropathy in Patients With ST-Segment Elevation Myocardial Infarction.

We evaluated the predictive value of admission systemic immune-inflammation index (SII) for the risk of contrast-induced nephropathy (CIN) in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and SII (platelet × NLR) levels were calculated in 1621 consecutive patients with STEMI. The relationship of these parameters with CIN development within 72 hours of pPCI was analyzed. Of the study population, 343 (21.1%) cases developed CIN. The frequency of CIN was 11.1% in the first SII quartile, 11.6% in the second SII quartile, 26.8% in the third SII quartile, and 35% in the fourth SII quartile, which differed significantly between groups (P < .01). Age, baseline glomerular filtration rate, contrast media volume, hypertension, C-reactive protein levels, and the quartiles of SII were independent predictors of CIN. Patients in the third SII quartile versus first SII quartile (OR: 2.906, 95% CI, 1.903-4.437; P < .001), and fourth SII quartile versus first SII quartile (OR: 4.168, 95% CI, 2.754-6.313; P < .001) had a significantly higher risk for CIN in the multivariable model. The SII may be a promising inflammatory parameter to predict CIN after pPCI.

Early outcomes of the t-Branch off-the-shelf multi-branched stent graft in 542 patients for elective and urgent aortic pathologies: A retrospective observational study

ObjectiveThe t-Branch, a standardized off-the-shelf multi-branched stent graft has been used for the treatment of elective and urgent cases in aortic disease. The aim of this study was to assess the early outcomes in terms of technical success, mortality, and morbidity in >500 patients being treated with the t-Branch device. MethodsA two-center retrospective observational study was undertaken including patients treated using the t-Branch (Cook Medical, Bloomington, IN) in elective or urgent settings for complex abdominal aortic aneurysm and thoraco-abdominal aortic aneurysm between 2014 and 2019 (early experience 2014-2016; late experience 2017-2019). Primary endpoints were technical success and early (30-day) mortality, and secondary endpoints were early morbidity, endoleak, and target vessel patency rates. Multivariable regression models were used to determine the independent association of risk factors with (1) mortality and (2) spinal cord ischemia. ResultsA total of 542 patients (mean age, 70.5 ± 8.5 years; 388 men [72%]; mean aneurysm diameter, 7.5 ± 2.5 cm) were included (63% elective; 90% thoraco-abdominal aortic aneurysm). The technical success rate was 97% (526/542) (elective, 96.7% [328/339] vs urgent, 97.6% [208/213]). The total 30-day mortality rate was 12.3% (8.5% in elective, 15% in symptomatic, and 30% in contained rupture). After multivariate regression analysis, the mortality rate was associated with older age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.03-1.11; P < .001) and with lower baseline glomerular filtration rate (OR, 0.98; 95% CI, 0.98-0.99; P < .001). In elective cases, the mortality rate was associated with a history of coronary artery disease (OR, 0.26; 95% CI, 0.09-0.73; P < .011) and higher body mass index (OR, 0.87; 95% CI, 0.77-0.98; P < .027). In urgent cases, the mortality rate was associated with older age, (OR, 1.07; 95% CI, 1.02-1.13; P < .010) and lower baseline glomerular filtration rate (OR, 0.97; 95% CI, 0.95-0.99; P < .001). The spinal cord ischemia rate was 10.5% (6.5% temporary, 4% permanent) and was associated with the early study period (OR, 2.01; 95% CI, 1.03-3.89; P < .038). The renal impairment rate was 13%, the stroke rate was 2.5%, and the myocardial infarction rate was 1.8%, whereas the access complications rate was 7.7%. On early computed tomography angiography, the primary patency rate for the right renal artery was 99.6%, for the left renal artery was 100%, for the superior mesenteric artery was 99.4%, and for the coeliac trunk was 99.8%. The endoleak I and III rates were 2.7% (15/542) and 2.7% (15/542), respectively. ConclusionsElective and urgent use of the t-Branch multi-branched off-the shelf stent graft showed high technical success and early target vessel patency rates. Early mortality and morbidity rates were acceptable.

Renal Safety of [177Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Compromised Baseline Kidney Function.

Simple SummaryRadioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is an effective antitumor-treatment in metastatic castration-resistant prostate carcinoma (mCRPC). Concerns of potential nephrotoxicity are based on renal tubular PSMA expression and the resulting radiopharmaceutical retention during RLT, but data confirming clinically significant renal toxicity are still lacking. In this study, n = 22 patients treated within a prospective patient registry (REALITY Study) with significantly impaired baseline kidney function were investigated for treatment-associated nephrotoxicity and the potential relationship with administered activities of [177Lu]Lu-PSMA-617. As opposed to prevailing concerns, glomerular filtration rate (GFR) improved significantly in our cohort of patients and no significant correlation between change in GFR and administered activities were found. As pre-treatment chronic kidney failure did not lead to detectable RLT-induced deterioration of renal function in our study, the nephrotoxic potential of [177Lu]Lu-PSMA-617 RLT may be overestimated. We suggest not to categorically exclude patients from enrolment to PSMA-RLT due to renal impairment.Background: Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is an effective antitumor-treatment in metastatic castration-resistant prostate carcinoma (mCRPC). Concerns of potential nephrotoxicity are based on renal tubular PSMA expression and the resulting radiopharmaceutical retention during RLT, but data confirming clinically significant renal toxicity are still lacking. In this study, patients with significantly impaired baseline kidney function before initiation of therapy were investigated for treatment-associated nephrotoxicity and the potential relationship with administered activities of [177Lu]Lu-PSMA-617. Methods: Twenty-two mCRPC patients with impaired renal function (glomerular filtration rate (GFR) ≤ 60 mL/min) who received more than two cycles of [177Lu]Lu-PSMA-617 RLT (median 5 cycles and median 6-week time interval between consecutive cycles) were analyzed in this study. Patients were treated within a prospective patient registry (REALITY Study, NCT04833517). Cumulative administered activities ranged from 17.1 to 85.6 GBq with a median activity of 6.5 GBq per cycle. Renal function was closely monitored during and after PSMA-RLT. Results: Mean pre-treatment GFR was 45.0 ± 10.7 mL/min. After two (22/22 patients), four (20/22 patients), and six cycles (10/22 patients) of RLT, a significant increase of GFR was noted (each p < 0.05). End-of-treatment GFR (54.1 ± 16.7 mL/min) was significantly higher than baseline GFR (p = 0.016). Only one patient experienced deterioration of renal function (change of CTCAE grade 2 to 3). The remaining patients showed no significant reduction of GFR, including follow-up assessments (6, 9, and 12 months), and even showed improved (10/22 patients) or unchanged (11/22 patients) CTCAE-based renal impairment grades during and after the end of PSMA-RLT. No significant correlation between the change in GFR and per-cycle (p = 0.605) or cumulative (p = 0.132) administered activities were found. Conclusions: As pre-treatment chronic kidney failure did not lead to detectable RLT-induced deterioration of renal function in our study, the nephrotoxic potential of [177Lu]Lu-PSMA-617 RLT may be overestimated and not of clinical priority in the setting of palliative treatment in mCRPC. We suggest not to categorically exclude patients from enrolment to PSMA-RLT due to renal impairment.

Impact of Morbid Obesity and Obesity Phenotype on Outcomes After Transcatheter Aortic Valve Replacement.

BackgroundThere is a paucity of outcome data on patients who are morbidly obese (MO) undergoing transcatheter aortic valve replacement. We aimed to determine their periprocedural and midterm outcomes and investigate the impact of obesity phenotype.Methods and ResultsConsecutive patients who are MO (body mass index, ≥40 kg/m2, or ≥35 kg/m2 with obesity‐related comorbidities; n=910) with severe aortic stenosis who underwent transcatheter aortic valve replacement in 18 tertiary hospitals were compared with a nonobese cohort (body mass index, 18.5–29.9 kg/m2, n=2264). Propensity‐score matching resulted in 770 pairs. Pre–transcatheter aortic valve replacement computed tomography scans were centrally analyzed to assess adipose tissue distribution; epicardial, abdominal visceral and subcutaneous fat. Major vascular complications were more common (6.6% versus 4.3%; P=0.043) and device success was less frequent (84.4% versus 88.1%; P=0.038) in the MO group. Freedom from all‐cause and cardiovascular mortality were similar at 2 years (79.4 versus 80.6%, P=0.731; and 88.7 versus 87.4%, P=0.699; MO and nonobese, respectively). Multivariable analysis identified baseline glomerular filtration rate and nontransfemoral access as independent predictors of 2‐year mortality in the MO group. An adverse MO phenotype with an abdominal visceral adipose tissue:subcutaneous adipose tissue ratio ≥1 (VAT:SAT) was associated with increased 2‐year all‐cause (hazard ratio [HR], 3.06; 95% CI, 1.20–7.77; P=0.019) and cardiovascular (hazard ratio, 4.11; 95% CI, 1.06–15.90; P=0.041) mortality, and readmissions (HR, 1.81; 95% CI, 1.07–3.07; P=0.027). After multivariable analysis, a (VAT:SAT) ratio ≥1 remained a strong predictor of 2‐year mortality (hazard ratio, 2.78; P=0.035).ConclusionsTranscatheter aortic valve replacement in patients who are MO has similar short‐ and midterm outcomes to nonobese patients, despite higher major vascular complications and lower device success. An abdominal VAT:SAT ratio ≥1 identifies an obesity phenotype at higher risk of adverse clinical outcomes.

The impact of baseline glomerular filtration rate on subsequent changes of glomerular filtration rate in patients with chronic kidney disease

Higher baseline glomerular filtration rate (GFR) may yield subsequent steeper GFR decline, especially in patients with diabetes mellitus (DM). However, this correlation in patients with chronic kidney disease (CKD) and the presence or absence of DM remains controversial. We conducted a longitudinal cohort study in a single medical center between 2011 and 2018. Participants with CKD stage 1 to 3A were enrolled and divided into DM groups and non-DM groups, and then followed up at least every 6 months. We used a linear mixed regression model with centering time variable to overcome the problem of mathematical coupling in the analysis of the relation between baseline GFR and the changes, and compared the results from correct and incorrect specifications of the mixed models. A total number of 1002 patients with 285 diabetic and 717 non-diabetic persons was identified. The linear mixed regression model revealed a significantly negative correlation between baseline GFR and subsequent GFR change rate in both diabetic group and non-diabetic group (r = − 0.44 [95% confidence interval [CI], − 0.69 to − 0.09]), but no statistical significance in non-diabetic group after within-subject mean centering of time variable (r = − 0.09 [95% CI, − 0.41 to 0.25]). Our study showed that higher baseline GFR was associated with a subsequent steeper GFR decline in the DM group but not in the non-DM group among patients with early-stage CKD. Exact model specifications should be described in detail to prevent from a spurious conclusion.

Association between physical performance and incidence of end-stage renal disease in older adults: a national wide cohort study

BackgroundPhysical frailty has previously been associated with adverse clinical outcomes in patients with end-stage renal disease (ESRD). This study aimed to determine whether impaired physical performance at baseline is associated with the incidence of ESRD, using a nationwide database.MethodsThe timed up-and-go (TUG) test was used to assess physical frailty in 1,552,781 66-year-old individuals, using health examination database records from the Korean National Health Insurance Service. As a primary endpoint, incident ESRD was defined operationally using healthcare claims data from the Korean Health Insurance Review and Assessment Service.ResultsOur results showed that baseline kidney function was significantly worse in individuals with TUG results of > 10 s compared to individuals with an intact TUG performance (≤10 s). Kaplan-Meier analysis showed a stepwise dose-response relationship between baseline physical performance and the incidence rate of ESRD (log-rank test P-value of < 0.001). An increasing ESRD incidence rate trend with poor physical performance remained significant after adjusting for characteristics such as baseline glomerular filtration rate and proteinuria.ConclusionPoor baseline physical performance was associated with an increased risk of ESRD, suggesting possible interactions between systemic frailty and vascular aging processes.

Assessing Risk of Rapid Progression in Autosomal Dominant Polycystic Kidney Disease and Special Considerations for Disease-Modifying Therapy

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of kidney failure, accounting for 5%-10% of cases. Predicting which patients with ADPKD will progress rapidly to kidney failure is critical to assess the risk-benefit ratio of any intervention and to consider early initiation of long-term kidney protective measures that will maximize the cumulative benefit of slowing disease progression. Surrogate prognostic biomarkers are required to predict future decline in kidney function. Clinical, genetic, environmental, epigenetic, and radiologic factors have been studied as predictors of progression to kidney failure in ADPKD. A complex interaction of these prognostic factors determines the number of kidney cysts and their growth rates, which affect total kidney volume (TKV). Age-adjusted TKV, represented by the Mayo imaging classification, estimates each patient's unique rate of kidney growth and provides the most individualized approach available clinically so far. Tolvaptan has been approved to slow disease progression in patients at risk of rapidly progressive disease. Several other disease-modifying treatments are being studied in clinical trials. Selection criteria for patients at risk of rapid progression vary widely among countries and are based on a combination of age, baseline glomerular filtration rate (GFR), GFR slope, baseline TKV, and TKV rate of growth. This review details the approach in assessing the risk of disease progression in ADPKD and identifying patients who would benefit from long-term therapy with disease-modifying agents.

Revised ISN/RPS 2018 classification of lupus renal pathology predict clinical remission.

A precise description of renal histological lesions and an appropriate classification of lupus nephritis are both essential for nephrologists to guide treatment and predict prognosis among patients. The prognostic value of ISN/RPS 2003 classification is controversial. A new classification for lupus nephritis was recently proposed, namely, the revised ISN/RPS 2018 classification. The study aimed to evaluate the predictive value of the clinical and pathological factors according to ISN/RPS 2018 classification on renal remission among patients with proliferative lupus nephritis. A total number of 41 patients with proliferative lupus nephritis on adequate renal biopsy specimen between 2017 and 2018 were included. Clinical and histological variables were tested for their association with renal remission. Univariate and multivariate logistic regression analysis were performed to identify independent predictors of renal remission after 24weeks of induction therapy. After induction therapy, 56.1% of patients reached complete and partial remission and 43.9% reached no remission. In univariate analyses, baseline glomerular filtration rate (GFR), presence of anti-DNA titer, cellular crescents, interstitial inflammation, glomerulosclerosis, interstitial fibrosis, tubular atrophy and total chronicity index strongly impacted renal response. After multivariate logistic regression analysis, we identified aging, presence of cellular crescents, and high total renal chronicity index as independent predictors of renal remission. Receiver operating characteristic (ROC) analysis revealed that baseline estimated GFR (AUC = 0.708; 95% CI 0.527-0.888), anti-DNA titer (AUC = 0.674; 95% CI 0.491-0.858), cellular crescent (AUC = 0.750; 95% CI 0.585-0.915) and renal chronicity index (AUC = 0.765; 95% CI 0.585-0.915) predicted renal remission. Combining all factors achieved a perfect score predicting renal response (AUC 0.924; 95% CI 0.840-1.000). The study identified baseline GFR, anti-DNA titer, cellular crescent, and high chronicity index according to revised ISN/RPS 2018 classification as important predictors of renal response after induction therapy in proliferative lupus nephritis.

Association of Glomerular Filtration Rate and Carotid Intima-Media Thickness in Non-Diabetic Chronic Kidney Disease Patients over a 4-Year Follow-Up.

Patients with chronic kidney disease (CKD) have increased risk of cardiovascular events. However, the association of glomerular filtration rate (GFR) and carotid intima-media thickness (CIMT) in non-diabetic CKD patients is under-investigated. This prospective study was conducted at University Clinical Hospital Mostar over a 4-year period and enrolled a total of 100 patients with stage 2 and 4 CKD (50 patients per group). Stage 4 CKD group had significantly higher baseline CIMT values (1.13 ± 0.25 vs. 0.74 ± 0.03 mm, P < 0.001), and more atherosclerotic plaques at the study onset (13 (26%) vs. 0 (0%), P < 0.001) compared to stage 2 CKD. A statistically significant 4-year increase in GFR (coefficient of 2.51, 3.25, 2.71 and 1.50 for 1-year, 2-year, 3-year and 4-year follow-up, respectively, P < 0.05) with non-significant CIMT alterations has been observed in stage 2 CKD. Furthermore, linear mixed effects analysis revealed significant decrease in GFR (coefficient of −6.69, −5.12, −3.18 and −1.77 for 1-year, 2-year, 3-year and 4-year follow-up, respectively, P < 0.001) with increase in CIMT (coefficient of 0.20, 0.14, 0.07 and 0.03 for 1-year, 2-year, 3-year and 4-year follow-up, respectively, P < 0.001) in stage 4 CKD. GFR and CIMT showed significant negative correlation in both CKD groups during all follow-up phases (P < 0.001). Furthermore, multiple linear regression analysis revealed significant independent prediction of CIMT by baseline GFR (B = −0.85, P < 0.001), while there was no significant prediction of CIMT with other covariates. In conclusion, this study demonstrates significant association of GFR and CIMT in non-diabetic stage 2 and stage 4 CKD during the 4-year follow-up.

Radical cystectomy and perioperative chemotherapy in octogenarians with bladder cancer.

We aimed to compare the treatment patterns and oncological outcomes, including postoperative morbidity and chemotherapy use, between octogenarians and patients <80 years of age who underwent radical cystectomy for bladder cancer. We conducted a retrospective analysis of 119 patients who underwent radical cystectomy for bladder cancer at our center between January 2013 and April 2019. Comorbidities, clinical and pathological data, 30-day postoperative morbidity, and perioperative chemotherapy use were compared between octogenarians (n=31) and younger patients (n=88). Cancer-specific and overall survival rates were estimated with the Kaplan-Meier method and compared between the groups. No significant differences were found between the age groups in the clinical and pathological findings, including Charlson comorbidity index, modified frailty index, albumin level, renal function, and TNM stage. The median followup for survivors was 19 months (interquartile range [IQR] 11-30). Major complications (Clavien-Dindo grade ≥3) and 30-day postoperative mortality rates did not differ between the age groups (p=0.3 and p=0.18, respectively). Despite no difference in baseline glomerular filtration rates, perioperative chemotherapy utilization rate was lower among octogenarians compared to younger patients (13% vs. 34%, p=0.03). Estimated two-year cancer-specific survival rates for octo-generians and younger patients were 40% and 75%, respectively. Similarly, estimated two-year overall survival rates were 30% and 69%, respectively. Both cancer-specific and overall survival rates were significantly lower in octogenarians (p=0.007 and p=0.001, respectively). Radical cystectomy in octogenarians results in comparable short-term outcomes as in younger patients. However, in the elderly population, perioperative chemotherapy utilization rates are lower and survival is inferior.

Prognostic Value of Mesangial C4d Staining in IgA Nephropathy: A Tunisian Study.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease. The main challenge in this disease is the evaluation of prognostic factors for end-stage renal disease (ESRD). The aim of our study was to assess the clinical and prognostic implications of C4d staining in primary IgAN. This was a retrospective study, including adults with primary IgAN. The study was conducted over a period of 10 years. Renal biopsies were scored according to the Oxford classification. C4d immunohistochemical staining was performed. We included 44 patients with a sex ratio of 2.6. The average age was 35.1 ± 11 years. Twenty-two patients (57%) had hypertension (HTN). The median proteinuria was 1.92 g/day. The median of the glomerular filtration rate was 47.66 mL/min/1.73 m2. According to the Oxford classification, mesangial proliferation, endocapillary proliferation, glomerulosclerosis, interstitial fibrosis and/or tubular atrophy and crescents were present in 41%, 36%, 86%, 34%, and 25 % of cases, respectively. We found positive glomerular C4d staining in 25 renal biopsies (57%). Age at diagnosis, mean arterial pressure, HTN, and baseline glomerular filtration rate were not correlated with C4d staining. On the other hand, proteinuria was significantly higher in patients with C4d-positive renal biopsy. The median follow-up duration was 30.5 months. Ten patients (23%) reached ESRD. At univariate analysis, positive C4d staining in more than 25% of glomeruli in patients without C1q deposition in the immunofluorescent study was associated with ESRD. Our study confirms the prognostic value of C4d staining in primary IgAN.

Molecular imaging of inflammation crosstalk along the cardio-renal axis following acute myocardial infarction.

Rationale: Acute myocardial infarction (MI) triggers a systemic inflammatory response including crosstalk along the heart-kidney axis. We employed radionuclide-based inflammation-targeted whole-body molecular imaging to identify potential cardio-renal crosstalk after MI in a translational setup.Methods: Serial whole-body positron emission tomography (PET) with the specific CXCR4 ligand 68Ga-Pentixafor was performed after MI in mice. Tracer retention in kidneys and heart was compared to hematopoietic organs to evaluate systemic inflammation, validated by ex vivo analysis and correlated with progressive contractile dysfunction. Additionally, 96 patients underwent 68Ga-Pentixafor PET within the first week after MI, for systems-based image analysis and to determine prognostic value for adverse renal outcome.Results: In mice, transient myocardial CXCR4 upregulation occurred early after MI. Cardiac and renal PET signal directly correlated over the time course (r = 0.62, p < 0.0001), suggesting an inflammatory link between organs. Ex-vivo autoradiography (r = 0.9, p < 0.01) and CD68 immunostaining indicated signal localization to inflammatory cell content. Renal signal at 7d was inversely proportional to left ventricular ejection fraction at 6 weeks after MI (r = -0.79, p < 0.01). In patients, renal CXCR4 signal also correlated with signal from infarct (r = 0.25, p < 0.05) and remote myocardium (r = 0.39, p < 0.0001). Glomerular filtration rate (GFR) was available in 48/96 (50%) during follow-up. Worsening of renal function (GFR loss >5 mL/min/1.73m2), occurred a mean 80.5 days after MI in 16/48 (33.3%). Kaplan-Meier analysis revealed adverse renal outcome for patients with elevated remote myocardial CXCR4 signal (p < 0.05). Multivariate Cox analysis confirmed an independent predictive value (relative to baseline GFR, LVEF, infarct size; HR, 5.27).Conclusion: Systems-based CXCR4-targeted molecular imaging identifies inflammatory crosstalk along the cardio-renal axis early after MI.

Renal and Hepatic Outcomes after Remdesivir Therapy in Coronavirus Disease-2019-Positive Patients with Renal Dysfunction at Baseline or after Starting Therapy.

We aimed to study the effect of remdesivir therapy on renal and hepatic function in coronavirus disease-2019 (COVID-19) patients with renal dysfunction at baseline or after starting therapy and identify the factors, if any, related to the efficacy of remdesivir therapy on patient outcome. Patients included in the study were those who met all the following criteria irrespective of baseline glomerular filtration rate [including those already on maintenance hemodialysis (HD)] or baseline deranged liver function test. (1) Age >18 years, (2) COVID-19 reverse transcriptase-polymerase chain reaction positive, (3) Meeting criteria for administration of remdesivir - [any one of the following: (a) COVID-19 pneumonia with respiratory rate >30/min or SPO2<94% on room air, (b) Acute respiratory distress syndrome (ARDS)]. (4) Renal dysfunction at baseline, during or within 48 h of completion of therapy. Thirty-four patients had renal dysfunction at baseline or developed it after remdesivir therapy - 16 were acute kidney injury (AKI), 10 chronic kidney diseases (CKD), four CKD stage 5D, and four were postrenal transplant. The overall mortality was 18/34 (52.9%). Eight out of 30 (26.66%) needed HD during or after therapy and of these, 15 died and among 15 survivors, 14 returned to their baseline renal function after cessation of therapy, one patient is still dialysis dependent. In the dialysis-dependent CKD (n = 4) subgroup, three died and one was discharged. In the postrenal transplant (n = 4) group, all developed AKI during or after the completion of therapy. None required HD, two returned to their baseline renal function, and two died. Only five had alanine aminotransferase elevation (×1 upper limit of normal) during or within 48 h of completion of therapy - three died and two returned to baseline. Lower PaO2/FiO2 (severe ARDS) (P = 0.0001), higher C-reactive protein (P = 0.022), higher serum lactate dehydrogenase (P = 0.038), and duration of symptoms before starting therapy (P = 0.05) were statistically significant variables at baseline associated with higher mortality. Remdesivir can be tried in moderate-to-severe COVID-19 cases with renal dysfunction as a complete recovery of renal function was noted in survivors. However, larger and well-controlled studies evaluating its safety and efficacy in patients with AKI and CKD are needed.

New Baseline Renal Function after Radical or Partial Nephrectomy: A Simple and Accurate Predictive Model.

Preoperative estimation of new baseline glomerular filtration rate after partial nephrectomy or radical nephrectomy for renal cell carcinoma has important clinical implications. However, current predictive models are either complex or lack external validity. We aimed to develop and validate a simple equation to estimate postoperative new baseline glomerular filtration rate. For development and internal validation of the equation, a cohort of 7,860 patients with renal cell carcinoma undergoing partial nephrectomy/radical nephrectomy (2005-2015) at the Veterans Affairs National Health System was analyzed. Based on preliminary analysis of 94,327 first-year postoperative glomerular filtration rate measurements, new baseline glomerular filtration rate was defined as the final glomerular filtration rate within 3 to 12 months after surgery. Multivariable linear regression analyses were applied to develop the equation using two-thirds of the renal cell carcinoma Veterans Administration cohort. The simplest model with the highest coefficient of determination (R2) was selected and tested. This model was then internally validated in the remaining third of the renal cell carcinoma Veterans Administration cohort. Correlation/bias/accuracy/precision of equation were examined. For external validation, a similar cohort of 3,012 patients with renal cell carcinoma from an outside tertiary care center (renal cell carcinoma-Cleveland Clinic) was independently analyzed. New baseline glomerular filtration rate (in ml/minute/1.73 m2) can be estimated with the following simplified equation: new baseline glomerular filtration rate = 35 + preoperative glomerular filtration rate (× 0.65) - 18 (if radical nephrectomy) - age (× 0.25) + 3 (if tumor size >7 cm) - 2 (if diabetes). Correlation/bias/accuracy/precision were 0.82/0.00/83/-7.5-8.4 and 0.82/-0.52/82/-8.6-8.0 in the internal/external validation cohorts, respectively. Additionally, the area under the curve (95% confidence interval) to discriminate postoperative new baseline glomerular filtration rate ≥45 ml/minute/1.73 m2 from receiver operating characteristic analyses were 0.90 (0.88, 0.91) and 0.90 (0.89, 0.91) in the internal/external validation cohorts, respectively. Our study provides a validated equation to accurately predict postoperative new baseline glomerular filtration rate in patients being considered for radical nephrectomy or partial nephrectomy that can be easily implemented in daily clinical practice.

Association between mid-term worsening renal function and mortality after transcatheter aortic valve replacement in patients with chronic kidney disease.

Chronic kidney disease (CKD), acute kidney injury (AKI) and worsening renal function at 30 days after transcatheter aortic valve replacement (TAVR) portend poor outcomes. We sought to evaluate the association between worsening renal function at 3-6months and mortality among patients with baseline renal dysfunction undergoing TAVR. This is a retrospective study of patients with glomerular filtration rate (GFR) < 60 ml/min undergoing TAVR between June 2011 and March 2019 at the Regional Cardiac Catheterization Lab at Kaiser Permanente Los Angeles. Worsening renal function at 3-6months post-TAVR was defined as: increase in serum creatinine >1.5 times compared to baseline, absolute increase of ≥0.3mg/dl, or initiation of dialysis. Of 683 patients reviewed, 176 were included in the analysis (median age 84 [IQR 79-88] years, 56% female). Of these, 27 (15.3%) had worsening renal function. AKI post-TAVR (OR 2.9, 95% CI 1.1-7.4, p= .03) and transfusion of ≥4units red blood cells (OR 8.4, 95% CI 1.2-59, p= .03) were independent predictors of worsening renal function. Worsening renal function increased risk for mortality (HR 2.2, 95% CI 1.17-4.27, p= .015) at a median follow-up of 691 days. Those with improved/stable function with baseline GFR < 60 ml/min had comparable mortality risk to those with baseline GFR ≥ 60 ml/min (18% vs. 16.5%; HR 1.1, 95% CI 0.72-1.75, p= .62). Among patients with baseline renal dysfunction, only 15% developed worsening renal function at 3-6months after TAVR, which was associated with increased mortality. Predictors for worsening renal function include AKI and blood transfusions. Preventative measures peri-procedurally and continued monitoring post-discharge are warranted to improve outcomes.