Measurement Of Filtration Rate Research Articles

Suboptimal monitoring and management in patients with unrecorded stage 3 chronic kidney disease in real-world settings: Insights from REVEAL-CKD.

Clinical practice guidelines for patients with chronic kidney disease (CKD) recommend regular monitoring and management of kidney function and CKD risk factors. However, the majority of patients with stage 3 CKD lack a diagnosis code, and data on the implementation of these recommendations in the real world are limited. To assess the implementation of guideline-directed monitoring and management practices in the real world in patients with stage 3 CKD without a recorded diagnosis code. REVEAL-CKD (NCT04847531) is a multinational, observational study of patients with stage 3 CKD. Eligible patients had ≥2 consecutive estimated glomerular filtration rate (eGFR) measurements indicative of stage 3 CKD recorded >90 and ≤730 days apart, lacked an International Classification of Diseases 9/10 diagnosis code corresponding to CKD any time before and up to 6 months after the second eGFR measurement. Testing of key measures of care quality were assessed. The study included 435,971 patients from 9 countries. In all countries, the prevalence of urinary albumin-creatinine ratio and albuminuria testing was low. Angiotensin-converting enzyme inhibitor, angiotensin receptor blocker and statin prescriptions were highly variable, and sodium-glucose cotransporter-2 inhibitor prescriptions remained below 21%. Blood pressure measurements were recorded in 20.2%-89.9% of patients. Overall, a large proportion of patients with evidence of stage 3 CKD did not receive recommended, guideline-directed monitoring and management. The variability in standard of care among countries demonstrates a clear opportunity to improve monitoring and management of these patients, most likely improving long-term outcomes.

Accuracy of Shorter Iohexol Glomerular Filtration Rate Measurement Protocols in Individuals with Preserved Kidney Function.

Measuring glomerular filtration rate (mGFR) using exogenous tracers is recommended in a number of settings. Plasma one-compartment multi-sample protocols (MSP) are the most commonly used with iohexol being the dominant tracer. The accuracy of MSP protocols has mostly been evaluated in the setting of reduced GFR where delayed initial and final samples are recommended. Much less is known about MSPs when GFR is not decreased, and the default protocol tends to include initial sampling at 120 minutes (min) and final sampling at 240 min post iohexol injection. The recent KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease includes research recommendations for the development of shorter more efficient mGFR protocols. The objective of this study was to assess the performance of shorter MSPs with earlier initial (60 and 90 min) and final (150, 180, and 210 min) sampling times in individuals with preserved GFR. Reference mGFR was calculated using 5 samples collected between 120-240 min. Four different combinations of shorter sampling strategies were investigated. Performance was evaluated using measurements of bias, precision, and accuracy (P2, P5, and mean absolute error). The mean reference mGFR of the 43 participants was 102.3 ± 13.7 ml/min/1.73m2. All shorter mGFRs had biases less than 1 ml/min/1.73m2 and mean absolute error less than 1.6 ml/min/1.73m2. All shorter mGFRs were within 5% of the reference mGFR, and the majority were within 2%. These results demonstrate that shortening the mGFR procedure in individuals with preserved GFR provides similar results to the current standard while significantly decreasing procedure time.

The Early Diagnosis and Treatment of Chronic Renal Insufficiency.

Chronic renal insufficiency (CRI) is becoming more common and has an increasing impact on public health. In Germany, approximately one in ten adults has CRI. Its most serious consequence is generally not the development of end-stage renal failure, but rather the markedly increased cardiovascular risk as kidney function declines. This review is based on the findings of a selective search in PubMed for literature about the treatment options for CRI, and on our overview of the existing guideline recommendations on diagnostic testing. Patients with diabetes mellitus and arterial hypertension are at especially high risk of developing CRI. For these patients, some of the guidelines recommend regular testing for albuminuria and measurement of the glomerular filtration rate (GFR), though sometimes only when specific risk constellations are present. The treatment of CRI has evolved in recent years. At first, aside from general measures, only RAS inhibitors were available as a specific therapy for CRI. With the extension of the approval of SGLT-2 inhibitors to non-diabetic CRI patients, the options for treatment have become wider. Two randomized controlled trials have revealed the benefit of SGLT-2 inhibitors with respect to their primary combined endpoints: time to a specified eGFR reduction and renal/cardiovascular death (HR 0.61 [0.51; 0.72] and 0.72 [0.64; 0.82]). The potential side effects and contraindications of SGLT-2 inhibitors must be taken into account. A further treatment option for diabetics with CRI has become available with the approval of the non-steroidal mineralocorticoid receptor antagonist finerenone. In patients with risk factors, renal function should be regularly tested.

#1413 High performance of ACLARA calculator of rat creatinine clearance for the chronic follow up of renal function

Abstract Background and Aims A neural network-based calculator to estimate rat creatinine clearance (ClCr), as a measurement of the glomerular filtration rate (GFR), from paired plasma creatinine concentration and body weight data has been recently developed [1]. Like human GFR estimating formulae, ACLARA averts long experimental procedures and reduces animal stress (by obviating the use of individual isolation in metabolic cages). This tool is publicly available for free use among the scientific community (https://idal.uv.es/aclara/). When collated with experimentally measured ClCr, ACLARA performs very well at comparing experiments in the whole, showing almost identical behavior of all experimental groups and conditions. Yet, ACLARA was trained mostly with data from short experiments involving acute changes in renal function, and from young rats. Fewer data from older animals was included in the development of the calculator. Thus, its field performance on longer evolution of renal function in adult rats has not yet been sufficiently validated. Accordingly, the aim of this work was to deepen in the assessment of ACLARA in the long-term evolution of rat ClCr. Method The evolution of measured (mClCr) versus ACLARA-estimated ClCr (eClCr) was compared at different time points over a period of 3 months in 20 male Wistar rats with chronic renal damage and 8 age-matched controls. In total, 176 data pairs of mClCr and eClCr were obtained. On the one hand, mClCr was determined by the usual experimental procedure [2]. Briefly, rats were allocated in metabolic cages to obtain 24-hour urine samples and urine flow (UF). Creatinine concentration was measured in the urine (Cru) and plasma (Crp) by a colorimetric assay based on the Jaffe's reaction, and mCrCl was then calculated as Cru x UF / Crp. On the other hand, eClCr was estimated with the ACLARA calculator from the corresponding Crp and body weight data. A Pearson's correlation study between mClCr and eClCr was carried out. Results Our results reveal that the information provided by the 90-day evolution of mClCr and eClCr is virtually identical at the whole experiment level (see Fig. 1). Furthermore, ACLARA seems to provide slightly more coherent and homogeneous information, as the considerable experimental error introduced by urine collection is averted in eClCr but present in mClCr. At the individual data level, ACLARA-estimated values are slightly lower than the corresponding measurements. The correlation between mClCr and eClCr was highly significant (r Pearson= 0.83; p < 0.0001). Conclusion ACLARA shows high performance at estimating CrCl in rats of growing age. Our results support its use also in chronic studies in which renal function must be evaluated. Funding This research was funded by grants from Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación (PI21/01226 and PI21/00548 co-funded by the European Union; and RICORS2040, RD21/0005/0004, co-funded by the European Union – NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR)) and from Consejería de Educación, Junta de Castilla y León (IES160P20), co-funded by FEDER funds. Joana Mercado-Hernández is recipient of a predoctoral fellowship from the Junta de Castilla y Leon (Spain) and the European Social Fund from the European Commission.

#1432 Prevalence, risks and treatment of incident chronic kidney disease stage 3-4: an observational study in Finland between 2016-2022

Abstract Background and Aims The rising burden of chronic kidney disease (CKD) calls for early detection and targeted interventions. Kidney-protective treatments (renin–angiotensin system inhibitors [RASis] and sodium-glucose co-transporter-2 inhibitors [SGLT2is]) can delay chronic kidney disease (CKD) progression, cardiovascular events and death. However, contemporary differences between CKD patients with and without type 2 diabetes (T2D) is limited. This study aimed to describe the prevalence, patient characteristics, the use of kidney protective treatments (RASi or SGLT2i) and event risks among patients with incident stage 3-4 CKD in Finland. Method We used comprehensive real-world clinical data from electronic health records from primary and hospital care in five municipalities in Finland between 1st January 2016 to 31st December 2022 to identify stage 3-4 CKD patients aged ≥18 years, defined as having either one estimated glomerular filtration rate (eGFR) measurement between 15 to 60 ml/min/1.73 m2 followed by a second one ≥90 days apart, or a registered CKD diagnosis. Two cohorts from primary care were identified: a prevalent cohort indexed at a fixed date, 1st Jan 2022 and an incident cohort indexed at the date of new CKD. The incident CKD patients were followed from CKD incident index date until death, emigration, or end of study on 31 December 2022. Analyses were also stratified by CKD patients with T2D and non-diabetes (T1D and gestational diabetes excluded), respectively. Risks were estimated as event rates per 1000 patient-years. The proportion of patients on/off treatment were estimates as a function of time and divided into pre- vs. post-index. Results In 2022 the prevalent cohort of 16,380 CKD stage 3-4 patients, represented a prevalence of 6.2% in the total background population of 263,383 individuals. The 12,129 incident Stage 3-4 CKD patients had a median eGFR of 55 ml/min/1.73 m2, similar in both non-T2D and T2D. Most patients were non-T2D; 73% (n = 8859). At index, 1.7% had a CKD diagnosis, lower in non-T2D (1.0%) vs T2D (3.5%) patients. The use of urine albumin creatinine ratio (UACR) was generally very low (21% had a measurement), 9% in the non-T2D and 53% in the T2D patients. Non-T2D, compared to T2D patients, were similar in age (76 vs 75 years) and had slightly less comorbidities like HF (12% vs 18%), myocardial infarction (9% vs 14%), stroke (15% vs 16%), atrial fibrillation (21% vs 25%) and less treated with statins (38% vs 64%). During follow-up, 10% had died within 1-year (97 deaths per 1000 patient years), similar in non-T2D (95 deaths per 1000 patient years) and T2D patients (104 deaths per 1000 patient years). One year risk of any hospitalization was also high, 49% and 64%, respectively. The use of kidney-protective treatments (renin angiotensin system inhibitor [RASi] or SGLT2i) at index (date of incident CKD) was lower in patients without T2D (47%) compared to those with T2D (69%). No change was observed in their use in the 12 months after incident CKD (Fig.). Finally, when studying the proportion of all non-T2D patients receiving SGLT2i after approval for CKD treatment, less than 1% of all CKD patients in the study group were treated with SGLT2i on 31st December 2022. Conclusion This study shows that CKD stage 3-4 is highly prevalent in Finland. Newly detected CKD stage 3-4 patients were little diagnosed and the use of UACR was low, especially among those who were non-diabetic. More than 2 out of 3 CKD patients were non-diabetic. Importantly, these non-diabetic CKD patients had similarly high disease burden, similar high risk of dying and had less kidney/cardiovascular prevention compared to those with T2D. The high mortality risks, substantial kidney-protective treatment inertia and UACR underutilization in stage 3-4 CKD patients all call for an urgent need for improved awareness and risk management, especially in the larger group of non-T2D.

#2022 Clinical outcomes in US patients initiating finerenone – a report from the FOUNTAIN platform

Abstract Background and Aims Evidence from clinical trials demonstrates that finerenone reduces the risk of cardiovascular and renal complications among patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). What is lacking is the evidence on finerenone use in real-world clinical practice. Method The present analysis is based on a longitudinal single-arm cohort study of patients initiating finerenone between July 2021 and August of 2023 and with prior diagnoses of CKD and T2D. Data were obtained from US electronic health records and insurance claims (OM1 Real-World Data CloudTM). CKD was defined as either having 1 diagnostic code for CKD stage 2-4 or unspecified stage, two estimated glomerular filtration rate (eGFR) measurements between 15 and 60 ml/min/1.73 m2, or two urine albumin to creatinine ratio (UACR) measurements over 30 mg/g; T2D was defined as having a diagnostic code for T2D. We described patient demographics, comorbidities, and comedications at baseline (365 days prior and including index date), and incidence rates of cardiovascular and renal outcomes, including eGFR and UACR changes over time. The presented analysis (NCT05703880) is part of the multi-national, multi-database observational research platform FOUNTAIN. Results We identified 28,056 new users of finerenone with prior CKD and T2D. The users had a mean (SD) age of 68.8 (10.8) years and 44.8% were female. Comorbidities of interest at baseline were hypertension (89.8%), cardiovascular disease (21.2%), neuropathy (13.4%), retinopathy (8.1%), heart failure (7.9%), and cerebrovascular disease (4.2%). Assessment of comedication use at baseline indicates that patients who initiate finerenone had exposure to renin–angiotensin system inhibitors (52.5%), sodium-glucose cotransporter-2 inhibitors (39.2%), or glucagon-like peptide-1 receptor agonists (27.4%) within 180 days prior to initiating finerenone. Overall, 82.5% of patients initiated finerenone at 10 mg/d, while 17.5% of patients started with 20 mg/d. Complete results including incidence rates of cardiovascular and renal outcomes, hyperkalemia events, and changes in kidney function measures (eGFR, UACR) during follow-up will be presented as part of the conference presentation. Conclusion Data from patients receiving finerenone as part of clinical practice in the USA suggest that finerenone is used concurrently with other renal and cardiovascular protective medication-classes recommended for patients with CKD and T2D.

#1122 Anaemia in CKD and cardiovascular risk; all cut from the same cloth?

Abstract Background and Aims Anaemia in chronic kidney disease (CKD) has been repeatedly associated with increased cardiovascular morbidity and mortality, but most studies have not investigated its longitudinal association by sex and age. Our aim was to study the association between haemoglobin (Hb) current value and the hazard of major adverse cardiovascular event (MACE) in specific subgroups of CKD patients defined by age and sex. Because erythropoiesis-stimulating agents (ESA) are incriminated to modify the effect of Hb level on the hazard of event for high level of Hb, we have here only focused in non-ESA users CKD patients. Method We used data from the CKD-REIN cohort, which included 3033 patients with moderate to severe CKD from 40 nationally representative nephrology clinics in France between 2013 and 2016. We included patients with at least one Hb, estimated glomerular filtration rate (eGFR), transferrin saturation (TSAT) or ferritin measurement. We studied all Hb measurements available until a first MACE defined as the first event among cardio-vascular death, myocardial infarction, stroke or hospitalization for acute heart failure; initiation of kidney replacement therapy; death from other causes; or initiation of ESA therapy, whichever came first. First, we estimated the individual trajectories of Hb, eGFR, TSAT, ferritin using multivariate share random effect joint model. Then, we estimated the association between Hb current value and MACE using a cause specific multivariate Cox model in 4 specific subgroups separately: women ≤ and >70 years, men ≤ and >70 years. All models were adjusted on current value of eGFR, TSAT, Ferritin, and baseline value of albumin-to-creatinine ratio, age, CKD aetiology, heart failure past history, alcohol consumption, iron treatment, antithrombotic and anticoagulant. When appropriate, spline functions were used for continuous variables to account for potential non-linear effects. Reference value of Hb for computing hazard ratio was 12 g/dL in women, and 13 in men according to current definition of anaemia. Results A total of 2742 patients were included in the analysis (median eGFR 33 ml/min/1.73 m2, median age at inclusion 69 years) together with 28423 Hb measurements (median of 13 per patient) collected during a median follow-up of 5.0 years. There were 551 women ≤70 (median Hb 12.4 g/dL, 34 (6.2%) MACE), 349 women > 70 (12.2 g/dL, 61 (17.5%) MACE), 1009 men ≤ 70 (13.4 g/dL, 104 (10.3%) MACE) and 833 men > 70 (13.0 g/dL, 163 (19.6%) MACE). No statistical significant association was found in males whatever their age (Hazard ratio of MACE for each 1 g/dL increase in Hb 1.0 (95% CI 0.9-1.1) in men < 70 and 0.9 (95% CI 0.8-1.1) in men > 70). For women, the hazard of MACE raised as the Hb values decreased, with a more pronounced increase in women > 70 (Fig. 1). For example, the hazard ratio for a Hb value of 10 g/dL compared to the reference was 2.0 (95% CI 0.9-4.7) in women < 70 and 3.3 (95% CI 1.5-7.2) in women > 70. Conclusion In non-ESA users CKD patients, anaemia is associated with the occurrence of MACE in females, especially those older than 70 years. These results raise question about a one-size-fits-all approach in the interpretation of low values of haemoglobin and anaemia management. It also suggests to evaluate the effect of anaemia therapies in men and women separately.

#1128 Accuracy of shorter iohexol glomerular filtration rate measurement protocols in individuals with preserved kidney function

Abstract Background and Aims Measuring glomerular filtration rate (mGFR) using exogenous tracers is recommended in a number of settings with plasma one-compartment multi-sample protocols (MSP) being the most commonly used and iohexol being the dominant tracer. The accuracy of MSP protocols has mostly been evaluated in the setting of reduced GFR where delayed initial and final samples are recommended. Much less is known about MSPs when GFR is not decreased and the default protocol tends to include initial sampling at 120 minutes and final sampling at 240 minutes post iohexol injection. The objective of this study was to assess the performance of shorter MSPs with earlier initial (60 and 90 minutes) and final (150, 180, and 210 minutes) sampling times in individuals with preserved GFR. Method Participants were recruited from a 4-year prospective, observational study evaluating the cardiovascular, renal, and bone health profile of young adults with Type 1 Diabetes. The reference mGFR was calculated using a plasma iohexol clearance one compartment slope intercept method with 5 samples collected between 120-240 minutes post iohexol injection. Four different combinations of shorter sampling strategies were investigated: 60-150 min, 60-180 min, 90-180 min and 90-210 min. Performance was evaluated using measurements of bias, precision, and accuracy (P2, P5, and mean absolute error). Results Mean age of the 43 participants was 23.9 ± 1.9 yrs with a mean eGFRCKiD-1 of 95.5 ± 15.9 ml/min/1.73 m2 and mean reference mGFR (120-240 min) of 102.3 ± 13.7 ml/min/1.73 m2. All exploratory shorter mGFRs performed well, with median biases less than 1 ml/min/1.73 m2 and mean absolute error less than 1.6 ml/min/1.73 m2. All shorter mGFRs were within 5% of the reference mGFR and the majority were within 2%. Conclusion These results demonstrate that shortening the mGFR procedure in individuals with preserved GFR provided very similar results to the current standard while significantly decreasing procedure time. The cost savings and improved feasibility of these shortened protocols should reduce some of the barriers to more widespread adoption of GFR measurement.

Evaluating the associations between compliance with CKD guideline component metrics and renal outcomes

Understanding the association between compliance to the Chronic Kidney Disease (CKD) guidelines in real-world clinical settings and renal outcomes remains a critical gap in knowledge. A comprehensive analysis was conducted using data from a national, multicenter CKD registry. This study included 4,455 patients with an estimated glomerular filtration rate (eGFR) measurement on the index date and eight additional metrics recorded within six months. These metrics comprised serum electrolyte levels, low-density lipoprotein cholesterol, hemoglobin, and the use of renin-angiotensin system inhibitors. The primary outcome was a composite of renal events, defined by a decline in eGFR to < 15 mL/min/1.73 m2 or a reduction of ≥ 30% in eGFR, confirmed by follow-up tests. Over a median follow-up of 513 days, 838 renal events were observed. High serum potassium levels (> 5.4 mmol/L) were associated with increased event rates compared to lower levels. Similarly, low serum sodium-chloride levels (< 33) correlated with higher event rates. Usage of renin-angiotensin system inhibitors, low serum calcium (< 8.4 mg/dL), and high uric acid levels (> 7.0 mg/dL) were also linked to increased events. Conversely, higher hemoglobin levels (≥ 13 g/dL) were associated with lower event rates. Compliance to guidelines, categorized into quartiles based on the number of met metrics, revealed a significantly reduced risk of events in the highest compliance group (meeting 8 metrics) compared to the lowest (0–5 metrics). Compliance to CKD guidelines in clinical practice is significantly associated with improved renal outcomes, emphasizing the need for guideline-concordant care in the management of CKD.

Determining steady-state trough range in vancomycin drug dosing using machine learning

BackgroundVancomycin is a renally eliminated, nephrotoxic, glycopeptide antibiotic with a narrow therapeutic window, widely used in intensive care units (ICU). We aimed to predict the risk of inappropriate vancomycin trough levels and appropriate dosing for each ICU patient. MethodsObserved vancomycin trough levels were categorized into sub-therapeutic, therapeutic, and supra-therapeutic levels to train and compare different classification models. We included adult ICU patients (≥ 18 years) with at least one vancomycin concentration measurement during hospitalization at Mayo Clinic, Rochester, MN, from January 2007 to December 2017. ResultThe final cohort consisted of 5337 vancomycin courses. The XGBoost models outperformed other machine learning models with the AUC-ROC of 0.85 and 0.83, specificity of 53% and 47%, and sensitivity of 94% and 94% for sub- and supra-therapeutic categories, respectively. Kinetic estimated glomerular filtration rate and other creatinine-based measurements, vancomycin regimen (dose and interval), comorbidities, body mass index, age, sex, and blood pressure were among the most important variables in the models. ConclusionWe developed models to assess the risk of sub- and supra-therapeutic vancomycin trough levels to improve the accuracy of drug dosing in critically ill patients.

The highlights of kidney transplantation in2023

In 2023, significant advances were made in various areas of kidney transplantation. Firstly, the use of a balanced crystalloid solution in the recipient appears to prevent the delay in graft function, unlike hypothermia in the donor and normothermic pulsatile perfusion. Understanding the pathophysiology of humoral rejection has progressed, highlighting the major role of HLA class II molecules and innate immune cells (NK and monocytes expressing FCGR3A). An automatic Banff classification algorithm has been developed to better categorize biopsies in currently known diagnoses. CXCL10, combined with other variables, seems effective in ruling out rejection, but its role in routine care is yet to be defined. Regarding cytomegalovirus (CMV), letermovir has been proven effective in preventing CMV disease in D+R- patients, with fewer hematological side effects. For R+ patients, monitoring CMV-specific T-cell immunity is suggested to reduce the duration of antiviral prophylaxis. The only innovation in immunosuppression is imlifidase for highly sensitized patients, guided by French recommendations. A new equation for glomerular filtration rate measurement has been developed for kidney transplant recipients, performing well across various analyzed stratifications. Finally, xenotransplantation is making a comeback this year, generating hope. However, the description of early humoral rejections involving innate immune cells indicates that adjustments are still needed before considering its widespread deployment.

Glomerular filtration rate measurement during platinum treatment for urothelial carcinoma: optimal methods for clinical practice

BackgroundWe assessed the accuracy of four estimated glomerular filtration rate (eGFR) methods: MDRD, Cockcroft–Gault, CKD-EPI, and Wright.MethodThe four methods were compared to measure GFR (mGFR) in patients with urothelial urinary tract cancer (T2-T4bNxMx) receiving platinum-based chemotherapy at Rigshospitalet, Copenhagen, from January 2019 to December 2021. Using standardized assays, creatinine values were measured, and mGFR was determined using Technetium-99 m diethylenetriaminepentaacetic acid (Tc-99 m-DTPA) or Cr-51-ethylenediaminetetraacetic acid (Cr-51-EDTA) plasma clearance. Patients (n = 146) with both mGFR and corresponding creatinine values available were included (n = 345 measurements).ResultsThe CKD-EPI method consistently demonstrated superior accuracy, with the lowest Total Deviation Index of 21.8% at baseline and 22.9% for all measurements compared to Wright (23.4% /24.1%), MDRD (26.2%/25.5%), and Cockcroft–Gault (25.x%/25.1%). Bland Altman Limits of agreement (LOA) ranged from − 32 ml/min (Cockcroft–Gault) to + 33 ml/min (MDRD), with CKD-EPI showing the narrowest LOA (− 27 ml/min to + 24 ml/min and lowest bias (0.3 ml/min). Establishing an eGFR threshold at 85 ml/min—considering both the lower limit of agreement (LOA) and the minimum cisplatin limit at 60 ml/min—allows for the safe omission of mGFR in 30% of patients in this cohort.ConclusionCKD-EPI equation emerged as the most suitable for estimating kidney function in this patient group although not meeting benchmark criteria. We recommend its use for initial assessment and ongoing monitoring, and suggest mGFR for patients with a CKD-EPI estimated GFR below 85 ml/min. This approach could reduce costs and decrease laboratory time for 30% of our UC patients.

High-Throughput Computing to Automate Population-Based Studies to Detect the 30-Day Risk of Adverse Outcomes After New Outpatient Medication Use in Older Adults with Chronic Kidney Disease: A Clinical Research Protocol.

Safety issues are detected in about one third of prescription drugs in the years following regulatory agency approval. Older adults, especially those with chronic kidney disease, are at particular risk of adverse reactions to prescription drugs. This protocol describes a new approach that may identify credible drug-safety signals more efficiently using administrative health care data. To use high-throughput computing and automation to conduct 700+ drug-safety cohort studies in older adults in Ontario, Canada. Each study will compare 74 acute (30-day) outcomes in patients who start a new prescription drug (new users) to a group of nonusers with similar baseline health characteristics. Risks will be assessed within strata of baseline kidney function. The studies will be population-based, new-user cohort studies conducted using linked administrative health care databases in Ontario, Canada (January 1, 2008, to March 1, 2020). The source population for these studies will be residents of Ontario aged 66 years or older who filled at least one outpatient prescription through the Ontario Drug Benefit (ODB) program during the study period (all residents have universal health care, and those aged 65+ have universal prescription drug coverage through the ODB). We identified 3.2 million older adults in the source population during the study period and built 700+ initial medication cohorts, each containing mutually exclusive groups of new users and nonusers. Nonusers were randomly assigned cohort entry dates that followed the same distribution of prescription start dates as new users. Eligibility criteria included a baseline estimated glomerular filtration rate (eGFR) measurement within 12 months before the cohort entry date (median time was 71 days before cohort entry in the new user group), no prior receipt of maintenance dialysis or a kidney transplant, and no prior prescriptions for drugs in the same subclass as the study drug. New users and nonusers will be balanced on ~400 baseline health characteristics using inverse probability of treatment weighting on propensity scores within 3 strata of baseline eGFR: ≥60, 45 to <60, <45 mL/min per 1.73 m2. We will compare new user and nonuser groups on 74 clinically relevant outcomes (17 composites and 57 individual outcomes) in the 30 days after cohort entry. We used a prespecified approach to identify these 74 outcomes. In each cohort, we will obtain eGFR-stratum-specific weighted risk ratios and risk differences using modified Poisson regression and binomial regression, respectively. Additive and multiplicative interaction by eGFR category will be examined. Drug-outcome associations that meet prespecified criteria (identified signals) will be further examined in additional analyses (including survival, negative-control exposure, and E-value analyses) and visualizations. The initial medication cohorts had a median of 6120 new users per cohort (interquartile range: 1469-38 839) and a median of 1 088 301 nonusers (interquartile range: 751 697-1 267 009). Medications with the largest number of new users were amoxicillin trihydrate (n = 1 000 032), cephalexin (n = 571 566), prescription acetaminophen (n = 571 563), and ciprofloxacin (n = 504,374); 19% to 29% of new users in these cohorts had an eGFR <60 mL/min per 1.73 m2. Despite our use of robust techniques to balance baseline indicators and to control for confounding by indication, residual confounding will remain a possibility. Only acute (30-day) outcomes will be examined. Our data sources do not include nonprescription (over-the-counter) drugs or drugs prescribed in hospitals and do not include outpatient prescription drug use in children or adults <65 years. This accelerated approach to conducting postmarket drug-safety studies has the potential to more efficiently detect drug-safety signals in a vulnerable population. The results of this protocol may ultimately help improve medication safety.

Shear wave elastography in chronic kidney disease - the physics and clinical application.

Chronic kidney disease is a leading public health problem worldwide. The global prevalence of chronic kidney disease is nearly five hundred million people, with almost one million deaths worldwide. Estimated glomerular filtration rate, imaging such as conventional ultrasound, and histopathological findings are necessary as each technique provides specific information which, when taken together, may help to detect and arrest the development of chronic kidney disease, besides managing its adverse outcomes. However, estimated glomerular filtration rate measurements are hampered by substantial error margins while conventional ultrasound involves subjective assessment. Although histopathological assessment is the best tool for evaluating the severity of the renal pathology, it may lead to renal insufficiency and haemorrhage if complications occurred. Ultrasound shear wave elastography, an emerging imaging that quantifies tissue stiffness non-invasively has gained interest recently. This method applies acoustic force pulses to generate shear wave within the tissue that propagate perpendicular to the main ultrasound beam. By measuring the speed of shear wave propagation, the tissue stiffness is estimated. This paper reviews the literature and presents our combined experience and knowledge in renal shear wave elastography research. It discusses and highlights the confounding factors on shear wave elastography, current and future possibilities in ultrasound renal imaging and is not limited to new sophisticated techniques.

Risk Factors for Developing Low Estimated Glomerular Filtration Rate and Albuminuria in Living Kidney Donors

Rationale & ObjectiveChronic kidney disease is associated with significant morbidity and mortality in the general population, but little is known about the incidence and risk factors associated with developing low eGFR and moderate-severe albuminuria in living kidney donors following nephrectomy. Study DesignRetrospective, population-based cohort study. Setting& Participants: Kidney donors in Alberta, Canada. ExposureDonor nephrectomy between May 2001 and December 2017. Outcome2 estimated glomerular filtration rate (eGFR) measurements <45 mL/min/1.73 m2 or 2 measurements of moderate or severe albuminuria from one-year post-donation onwards that were at least 90 days apart. Analytical ApproachAssociations between potential risk factors and the primary outcome were assessed using Cox proportional hazard regression analyses. ResultsOver a median follow-up period of 8.6 years (interquartile range [IQR]: 4.7-12.6 years), 47 of 590 donors (8.0%) developed sustained low eGFR or moderate-severe albuminuria, with an incidence rate of 9.2 per 1000 person-years (95% confidence interval: 6.6-11.8). The median time for development of this outcome beyond the first year after nephrectomy was 2.9 years (IQR: 1.4-8.0 years). Within the first four years of follow-up, a 5 mL/min/1.73 m2 lower pre-donation eGFR increased the hazard of developing post-donation low eGFR or moderate-severe albuminuria by 26% (aHR, 1.26; 95% CI, 1.10-1.44). Furthermore, donors were at higher risk of developing low eGFR or albuminuria if they had evidence of pre-donation hypertension (aHR, 2.52; 95% CI, 1.28-4.96) or post-donation diabetes (aHR, 4.72; 95% CI, 1.54-14.50). LimitationsWe lacked data on certain donor characteristics that may impact long-term kidney function such as race, smoking history, and transplant-related characteristics. ConclusionsA proportion of kidney donors, at an incidence rate of 9.2 per 1,000 person-years, will develop low eGFR or albuminuria after donation. Donors with lower pre-donation eGFR, pre-donation hypertension, and post-donation diabetes are at increased risk of developing this outcome.

Assessment of Iohexol Serum Clearance by LC-MS/MS with Isotopically Labeled Internal Standard.

Accurate measurement of the glomerular filtration rate (GFR) is essential for detecting renal insufficiency in living kidney donors. Iohexol is a "near-ideal" exogenous filtration marker for GFR measurement that has attracted increasing interest in clinical practice because it is non-toxic, non-radioactive, readily available, and easy to measure. In this chapter, we describe a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to measure iohexol in serum and to calculate GFR based on the rate of iohexol clearance. In this procedure, the contrast agent iohexol is administrated to the study subject in an outpatient setting, and three timed blood samples are collected. The serum proteins are precipitated, and the supernatant containing iohexol and the internal standard 2H5-iohexol is diluted prior to LC-MS/MS analysis. The LC-MS/MS method utilizes a Thermo Vanquish UHPLC coupled with TSQ Endura triple quadruple mass spectrometer, with a total run time of 2.5min. The LC-MS/MS method has demonstrated good analytical performances, and the workflow can be used to reliably measure GFR in apparently healthy individuals without impaired renal function, such as living kidney donors.

Prevalence of chronic kidney disease in the Netherlands and its cardiovascular and renal complications

BackgroundKnowledge on prevalence, comorbidities and consequences of chronic kidney disease (CKD) is mandatory to estimate the potential of cardiovascular risk management on a population level. We studied the prevalence of CKD with or without type 2 diabetes mellitus (T2D) and/or heart failure and its cardiorenal complications in The Netherlands.MethodsA descriptive cross-sectional and longitudinal cohort study was performed, using data from the Dutch PHARMO Data Network. Prevalence of CKD at a single time point was determined by a recorded diagnosis or by ≥ 2 estimated glomerular filtration rate (eGFR) measurements and urine albumin/creatinine ratio (UACR) that define CKD. A representative group of adults with CKD was included in a longitudinal analysis to study cardiorenal complications. Those were followed until first complication, end of study or death, whichever occurred first.ResultsThe prevalence of CKD was 8.9% in a representative population of 2,187,962 adult Dutch individuals. The average age of persons with CKD was 72 years, 57% were female, 19.9% had T2D, 7.7% heart failure, and 3.0% both T2D and heart failure. In the longitudinal analysis, cerebrovascular events (11/1,000 person-years), hospitalizations for heart failure (10/1,000 person-years), myocardial infarction (5.5/1,000 person-years), and hospitalization for CKD (6.2/1,000 person-years) were the most common first cardiorenal complications. People with CKD with T2D and/or heart failure generally had higher rates of cardiovascular or renal complications or mortality than people with CKD without these comorbidities.ConclusionThe prevalence of CKD in The Netherlands is 8.9%. People with T2D or heart failure, or both, in addition to CKD, had numerically higher mortality and cardiorenal complication rates than people without these comorbidities. Optimizing up-to-date cardiovascular risk management in these high-risk individuals may provide health benefits.

Combination of robot-assisted laparoscopy and ureteroscopy for the management of complex ureteral strictures

BackgroundTo summarize the efficacy of combined robot-assisted laparoscopy and ureteroscopy in treating complex ureteral strictures.MethodsEleven patients underwent combined robot-assisted laparoscopy and ureteroscopy for ureteral strictures between January 2020 and August 2022. Preoperative B-ultrasound, glomerular filtration rate measurement, and intravenous pyelography showed different degrees of hydronephrosis in the affected kidney and moderate to severe stenosis in the corresponding part of the ureter. During the operation, stricture segment resection and end-to-end anastomosis were performed using the da Vinci robot to find the stricture point under the guidance of a ureteroscopic light source in the lateral or supine lithotomy position.ResultsAll the patients underwent robot-assisted laparoscopy and ureteroscopy combined with end-to-end ureterostenosis. There were no conversions to open surgery or intraoperative complications. Significant ureteral stricture segments were found in all patients intraoperatively; however, stricture length was not significantly different from the imaging findings. Patients were followed up for 3–27 months. Two months postoperatively, the double-J stent was removed, a ureteroscopy was performed, the ureteral mucosa at the end-to-end anastomosis grew well, and the lumen was patent in all patients. Furthermore, imaging examination showed that hydronephrosis was significantly improved in all patients, with grade I hydronephrosis in three cases and grade 0 hydronephrosis in eight cases. No recurrence of ureteral stricture was observed in patients followed up for > 1 year.ConclusionRobot-assisted laparoscopy combined with ureteroscopy is an effective method for treating complex ureteral strictures and can achieve accurate localization of the structured segment.

Accuracy-Based Glomerular Filtration Rate Assessment by Plasma Iohexol Clearance in Kidney Transplant Donors.

An accurate measurement of the glomerular filtration rate (GFR) is essential for detecting renal insufficiency in living kidney donors. Iohexol is a "near-ideal" exogenous filtration marker for GFR measurements that has attracted increasing interest in clinical practice because it is non-toxic, non-radioactive, readily available, and easy to measure. In this study, we aimed to set up a laboratory test to conveniently assess the plasma clearance of iohexol in living kidney donors. A workflow was established in the institution's infusion clinic to administer iohexol and to collect three timed blood samples from renal transplant donors. Iohexol was thereafter measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The serum proteins were precipitated and the supernatant containing iohexol was diluted prior to the LC-MS/MS analysis. The LC-MS/MS method was developed on a Thermo Vanquish UHPLC coupled with a TSQ Endura triple quadruple mass spectrometer with a total run time of 2.5 min. The analytical performance of the method was assessed. The LC-MS/MS method demonstrated a good analytical performance. To calculate the iohexol clearance rate and the GFR, automated data integration and a result calculation were accomplished by using a custom Python script. Automated result reporting was achieved using a laboratory informatics system (LIS) vendor's direct media interface. We developed and implemented a laboratory test to assess the plasma clearance of iohexol. A workflow was established in the hospital to reliably measure the GFR in living kidney donors, with a potential to be further expanded into other areas where an accurate GFR measurement is needed.

Preoperative chronic kidney disease and complications after pancreatoduodenectomy: a retrospective cohort study.

Chronic kidney disease is a prevalent condition in surgical patients. Possible associations with increased postoperative morbidity and mortality have not been clearly demonstrated in patients undergoing pancreatoduodenectomy. The aim of this study was to assess the risk of postoperative complications in patients with reduced kidney function undergoing pancreatoduodenectomy. All patients undergoing pancreatoduodenectomy at Karolinska University Hospital between 2008 and 2019 were retrospectively included. The variable of interest was chronic kidney disease, based on preoperative estimated glomerular filtration rate measurements. Unadjusted and adjusted logistic regression analyses were performed for standardized postoperative complications. A total of 971 patients were included in the study, of whom 92 (10%) had an estimated glomerular filtration rate < 60 mL/min/1.73m2 , equivalent to chronic kidney disease Stage 3a or worse. Patients with chronic kidney disease had a higher odds of longer hospital stay (adjusted odds ratio 1.58, 95% confidence interval 1.00-2.50) and postoperative weight increase (adjusted odds ratio 2.02, 1.14-3.56). A 10 unit increase of preoperative estimated glomerular filtration rate was associated to lower odds of intensive care unit admission (adjusted odds ratio 0.81, 0.69-0.95), delayed gastric emptying (adjusted odds ratio 0.90, 0.81-0.99), and post-operative pancreatic fistula (adjusted odds ratio 0.83, 0.74-0.94). Patients undergoing pancreatoduodenectomy with decreased preoperative kidney function are more likely to experience major postoperative complications, and also postoperative weight increase. Preoperative kidney function assessment is important in risk stratification before pancreatoduodenectomies.