Mean eGFR Research Articles

Pharmacokinetic Properties of Dapagliflozin in Patients with Stage 4 Chronic Kidney Disease.

The pharmacokinetic data on dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, is limited in patients with severe renal impairment. We aimed to evaluate the pharmacokinetic properties and safety of dapagliflozin in patients with chronic kidney disease (CKD) stage 4. This was a single center, open label, pharmacokinetic trial involving single and multiple doses. Patients with an estimated glomerular filtration rate (eGFR) of 15-<30 mL/min/1.73m2 were enrolled. The single-dose group received 10mg of oral dapagliflozin once daily, while the multiple-dose group received 10mg daily for five days. Pharmacokinetic parameters, pharmacodynamic response and tolerability were assessed. A total of 12 participants completed the single-dose study, and 9 participants completed the multiple-dose study. The mean eGFR was 23.4 and 23.2 mL/min/1.73m2 in single and multiple dose group, respectively. In the single dose group, dapagliflozin was rapidly absorbed and metabolized to produce dapagliflozin 3-O-glucuronide (D3OG) , with a mean Tmax of 0.7 hours and 1.8 hours, and a mean T1/2 of 16.7 hours and 14.9 hours, respectively. Participants with an eGFR of 15-24 mL/min/1.73m2 exhibited higher AUC0-∞ and mean residence time (MRT) for D3OG compared to those with an eGFR of 25-30 mL/min/1.73m2. In the multiple-dose group, there was no significant accumulation of dapagliflozin, as indicated by the ratio of AUCTau (918.6 ± 155.2 h×ng/mL) to AUC0-24h (917.1 ± 154.7 h×ng/mL) was close to 1. In the multiple-dose group, UACR decreased by 21% and 24-hour urinary protein decreased by 23% from baseline to 24 hours after the last dose. In conclusion, no clinically significant accumulation of dapagliflozin was observed in patients with stage 4 CKD.

Switching from ARBs to sacubitril/valsartan safely improves 24-hour ambulatory blood pressure in patients with advanced chronic kidney disease

Abstract Background We investigated the effects of sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), on 24-hour blood pressure (BP) and safety for 12 weeks in Japanese patients with non-dialysis advanced chronic kidney disease (CKD). Methods We conducted a prospective, single-arm exploratory study. Patients with non-dialysis CKD stage G4-5 (estimated glomerular filtration (eGFR) &amp;lt;30 mL/min/1.73 m2) who did not achieve their BP goals with angiotensin receptor blocker (ARB) administration, were enrolled and switched to sacubitril/valsartan. Primary and key secondary endpoints were changes from baseline in the 24-hour systolic BP (SBP) measured via ambulatory BP monitoring (ABPM) over 12 weeks and the safety, especially incidence of serum creatinine (Cr) increase (≥30% increase from baseline) and hyperkalemia. Results Thirty patients were enrolled, and 29 patients were switched to sacubitril/valsartan. Efficacy analysis was conducted on 26 patients. Baseline mean eGFR and office BP were 21.1±5.0 mL/min/1.73m2 and 149.4±23.7/80.7±11.9 mmHg, respectively. Baseline 24-hour, daytime, and nighttime BP were 139.6±17.7/77.0±7.8 mmHg, 143.5±18.5/79.6±8.7 mmHg, and 131.0±20.4/71.1±8.8 mmHg, respectively. After 12 weeks, changes in 24-hour, daytime, and nighttime SBP from baseline were -7.1±12.4 mmHg (P &amp;lt;0.01), -7.7±12.9 mmHg (P &amp;lt;0.01), and -5.8±15.8 mmHg (P = 0.07), respectively. No incidences of potassium values &amp;gt;6.0 mmol/L or serum Cr ≥30% increase from baseline were reported after sacubitril/valsartan initiation. Conclusions Switching from ARB to sacubitril/valsartan can safely enhance 24-hour antihypertensive treatment in patients with non-dialysis CKD G4-5 who do not achieve BP goals with ARBs. CLINICAL TRIALS REGISTRATION: Trial Number jRCT1031220149.

Prognostic Value of Blood Pressure Rhythmicity for Estimated Glomerular Filtration Rate in Male Hypertensive Patients Aged 55 and Older

Background: Blood pressure (BP) exhibits a circadian rhythm characterized by higher levels during wakefulness and lower levels during sleep; however, the functional and structural impact of the rhythms of BP remains uncertain. Methods: Two hundred hypertensive males aged 55 and older without overt cardiovascular or cerebrovascular diseases were enrolled in this longitudinal study. Of these, 188 were included in the analyses (12 lacked valid BP records for part of the 24 h period). Rhythmic profiling of BP was performed using ARSER, and rhythmicity was considered significant at P &lt; 0.05. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology (CKD–EPI) formula. The primary outcome was the change in eGFR. Results: The average age was 64.9±7.2 years. For systolic BH (SBP), 38 of the subjects exhibited a 12 h rhythm and 43 subjects a 24 h rhythm; for DBP, 38 exhibited a 12 h rhythm and 36 exhibited a 24 h rhythm. During the three-year follow-up period, 16 of the subjects died and 36 were lost to follow-up. The mean eGFR at baseline and follow-up were, respectively, 86.6 ± 14.0 and 81.0 ± 17.1 mL min−1 1.73 m−2 (P = 0.001). The urinary albumin:creatinine ratio did not vary significantly among the groups (P = 0.059). Subjects with 12 h rhythmic SBP exhibited a smaller reduction in eGFR than those with arrhythmic SBP (P = 0.014). However, the changes in eGFR were similar among the groups displaying 12 h or 24 h rhythmic DBP or arrhythmic DBP. We defined a decline in eGFR as a reduction &gt;1/2 SD between baseline and follow-up. Adjusting for confounding factors (including age, smoking, alcohol consumption, diabetes mellitus, BMI, albumin levels, administration time of antihypertensive drugs, and duration of hypertension), the risk of a decline in eGFR was 70% lower in subjects with 12 h rhythmic SBP than in those with arrhythmic SBP (heart rate [HR] = 0.307 [0.108–0.874], P = 0.027). Conclusion: SBP with a 12 h period is a protective predictor of the decline in eGFR in hypertensive males. It is therefore necessary to focus on the rhythmic profiling of BP.

Efficacy and safety of Kunxian in IgA nephropathy

BackgroundKunxian (KX) has been reported to be effective in treating Immunoglobulin A nephropathy (IgAN) and autoimmune disorders, such as lupus nephritis, but there is a lack of controlled trial on its effectiveness and safety for treating IgAN.MethodsThis multicenter, prospective cohort study was conducted with individuals aged 18–60 years with biopsy-confirmed primary IgAN, proteinuria greater than 0.75 g/d, and estimated glomerular filtration rate (eGFR) greater than 60 mL/min/1.73 m2. Patients were treated with KX or Mycophenolate mofetil (MMF) after receiving a stable dose of an angiotensin-converting-enzyme inhibitor or angiotensin-receptor blocker for at least 4 weeks.Results67 patients were assigned to the KX group and 72 to the MMF group. The mean (standard deviation) eGFR was 87.75 (15.94) mL/min/1.73 m2, and the mean (standard deviation) proteinuria was 1.70 (0.74) g/d. Patients in the KX group had a greater reduction in proteinuria than those in the MMF group did. Complete remission occurred in 43 patients (64.2%) in the KX group and 37 patients (51.4%) in the MMF group (hazard ratio [HR] 0.612, 95% CI 0.385–0.972, P = 0.038). Overall response occurred in 59 participants (88.1%) in the KX group and 59 participants (81.9%) in MMF group (HR 0.658, 95% CI 0.447–0.970, P = 0.034). Adverse events were observed in 6 patients (8.9%) in the KX group and 5 patients (6.9%) in the MMF group with no significant difference.ConclusionCompared with MMF, KX was safe and significantly decreased proteinuria in IgAN.

Kidney function decline improves after lithium discontinuation.

Long-term lithium treatment decreases kidney function. However, it remains unclear whether stopping lithium improves kidney function. To study kidney function in patients who stopped and subsequently restarted lithium treatment. Mirror-image design using data from the LiSIE retrospective cohort study. The mirror was set to when lithium was stopped with a 5-year pre- and post-mirror period. Adult patients with bipolar, schizoaffective disorder or unipolar depression, who had lithium ≥4.5 years in the pre-mirror period, were included. Creatinine measurements were available from 1997 to 2017. The main outcome was the difference in mean annual change of the estimated glomerular filtration rate (eGFR) adjusted for sex, hypertension and diabetes mellitus. A total of 168 participants (94 women, 74 men) were included. Mean annual eGFR change was -1.58 (-1.87 to -1.28)mL/min/1.73m2/year before and -0.023 (-0.49 to +0.44)mL/min/1.73m2/year after lithium discontinuation (p<0.0001 for difference). The improvement was 0.77 (0.35-1.20)mL/min/173m2/year in participants with eGFR >60mL/min/1.73m2, and 3.03 (2.15-3.92)mL/min/1.73m2/year for participants with eGFR <30mL/min/1.73m2. The effect was persistent over the 5-year post-mirror study period. For participants restarting lithium, the mean annual eGFR change was -1.71 (-2.26 to -1.16)mL/min/1.73m2/year, a setback compared to their lithium-free post-mirror period (p<0.0001). We did not see any difference compared to the pre-mirror period (p=0.51). Stopping lithium slowed down mean eGFR decline. This effect was more pronounced in participants with lower eGFR at the time of lithium discontinuation. In participants who restarted lithium, the annual decline of eGFR reverted to pre-lithium discontinuation levels.

Comparative Analysis of Long-Term Renal Outcomes in Upper Tract Urothelial Carcinoma: Local Ablation Versus Radical Nephroureterectomy

(1) Background: Upper tract urothelial carcinoma (UTUC) is typically managed through radical nephroureterectomy (RNU) or local ablation (LA). Compared to RNU, LA offers nephron-sparing benefit for select patients but may present increased recurrence risk. This study primarily compares long-term differences between LA and RNU in chronic kidney disease (CKD) progression, estimated glomerular filtration rate (eGFR) decline, all-cause mortality, and need for dialysis. (2) Methods: A retrospective cohort study was conducted using the TriNetX database, examining patients with UTUC treated with RNU (n = 2007) or LA (n = 4172). Propensity score matching balanced both cohorts (n = 1965 per group). Risk ratios and hazard ratios with 95% confidence intervals were calculated over 10 years. (3) Results: At 10 years, LA preserved higher mean eGFR (53.49 vs. 46.72; p &lt; 0.001) and lower mean creatinine (1.56 vs. 1.66; p = 0.017). However, LA held a higher incidence of end-stage renal disease (ESRD) (3.6% vs. 2.2%, p = 0.008) and all-cause mortality (26.7% vs. 23.5%, p = 0.016). There was no significant difference in rates of dialysis (p = 0.79). (4) Conclusions: RNU did not carry an increased risk of ESRD, advanced stages of CKD, need for renal dialysis, or overall mortality compared with LA. LA may delay but not totally prevent renal dysfunction when compared to RNU, and exhibits a more gradual timeline.

Validation of the Beck Depression Inventory in U.S. Hispanic Patients with Chronic Kidney Disease.

Depression is common in patients with chronic kidney disease (CKD). Self-report scales including the Beck Depression Inventory (BDI) have been evaluated in non-Hispanic adults with CKD for screening of depressive symptoms. However, the BDI has not been validated in Hispanic adults with CKD. We investigated the screening characteristics of the BDI in 248 Hispanic adults (164 with CKD and 84 with end-stage kidney disease [ESKD]) enrolled in the Hispanic Chronic Renal Insufficiency Cohort Study. Two trained study personnel administered the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Disorders (SCID) which served as the gold standard measure for the diagnosis of major depression. Among the 164 participants with CKD, mean (SD) age was 61 (0.8) years, 37% were female, 77% spoke primarily Spanish, mean (SD) eGFR was 37 (1.3) ml/min/1.73m2 and median (IQR) proteinuria was 0.4 (0.1-2.0) g/g. Using the SCID, 24 (15%) were classified as having current major depressive disorder. The best cutoff BDI score to identify current major depression disorder based on the receiver operating characteristics curve was 16. Sensitivity was 88%, specificity was 84%, positive predictive value was 49% and negative predictive value was 98%. Similar results were found in participants with ESKD. A BDI score of ≥16 was sensitive and specific for identifying major depression in U.S. Hispanic adults with CKD and ESKD, which is a higher cutoff than reported for non-Hispanic patients with CKD. These differences in psychometric properties should be considered in future research and clinical practice.

Comprehensive modalities of kidney-sparing treatment in a carefully selected cohort of localized high-risk upper tract urothelial carcinoma: A potential paradigm shift.

794 Background: This study aims to assess the efficacy and safety of comprehensive modalities of kidney-sparing treatment in a carefully selected cohort of patients with localized high-risk upper tract urothelial carcinoma (UTUC). Methods: This study was initiated in January 2019 and is ongoing. Selected localized high-risk UTUC patients, characterized by conditions such as solitary kidney, bilateral tumors, impending renal insufficiency or patient refusal/ineligibility for radical nephroureterectomy (RNU), were included. Systemic therapy regimens were tailored to patient characteristics, tumor pathology and biomarkers, and included platinum-based chemotherapy, Disitamab Vedotin, and immune checkpoint inhibitors (ICIs). After endoscopic biopsy and attempted laser ablation, patients received four cycles of systemic induction therapy, followed by maximal endoscopic laser ablation or segmental ureterectomy. Postoperatively, a one-year course of immunotherapy maintenance was administered. The co-primary endpoints were disease-free survival (DFS) and conversion-free survival (CFS). Secondary endpoints included metastasis-free survival (MFS), renal function changes, ureteral stricture and treatment safety. Results: 68 patients were enrolled, with a follow-up of 18 months. 54 patients underwent endoscopic thulium laser tumor ablation, while 14 underwent segmental ureterectomy. The induction therapy comprised Disitamab Vedotin for 32 patients, platinum-based chemotherapy for 9, and immunotherapy for 37. Urothelial tract recurrence was observed in 28 patients with a 1-yr DFS rate was 58.82%, who subsequently underwent repeat endoscopic laser ablation. Salvage RNU was performed in 9 patients, yielding a 1-yr CFS rate of 93.7% and a 2-yr CFS rate of 88.9%. No distal metastasis was reported. Postoperative renal function impairment was noted in 15 patients (22.06%). Mean eGFR improvements were observed at various time points: 3.15 ml/min/1.73m 2 at 1 months, 5.07 ml/min/1.73m 2 at 3 months, 2.41 ml/min/1.73m 2 at 6 months, and 3.97 ml/min/1.73m 2 at 12 months. Ureteral stricture on the affected side was a common complication, which was more likely to occur in patients who underwent 3 or more times of ureteroscopy (9/27). Notably, no grade 3 or higher systemic toxicities were observed. Conclusions: Preliminary findings indicate that our comprehensive modalities of kidney-sparing treatment demonstrated promising tumor control and satisfactory renal function preservation in a carefully selected cohort of localized high-risk UTUC. Its definite application strategy and value should be further evaluated in future clinical practice.

Kidney-sparing approach for selected localized high-risk upper tract urothelial carcinoma: A pilot study combining endoscopic thulium laser ablation with perioperative disitamab vedotin and immune checkpoint inhibitors.

791 Background: Radical nephroureterectomy (RNU) is the standard treatment for localized high-risk upper tract urothelial carcinoma (UTUC). However, the predominance of UTUC in elderly populations with significant comorbidities necessitates alternative treatment strategies that prioritize functional nephron preservation. This pilot study aims to assess the efficacy and safety of a comprehensive modality of kidney-sparing approach, comprising endoscopic Thulium laser ablation and perioperative systemic therapy (Disitamab vedotin [DV] and immune checkpoint inhibitors [ICIs]), in a carefully selected cohort of localized high-risk UTUC. Methods: This ongoing study, initiated in November 2021 at West China Hospital of Sichuan University, included selected patients with localized UTUC patients (cT≤2N0M0) characterized by conditions such as solitary kidney, bilateral tumors, impending/already renal insufficiency and individual refusal/ineligibility for RNU. The treatment protocol consisted of endoscopic biopsy and initial laser ablation, followed by 3-4 cycles of DV and ICIs administered every three weeks as induction therapy. Subsequently, patients underwent maximal endoscopic laser ablation. Those exhibiting efficient response received a 6-month course of DV and a 12-month course of ICIs as maintenance therapy. Co-primary endpoints were 1-yr disease-free survival (DFS) and conversion-free survival (CFS). Secondary endpoints included clinical complete response (cCR) rate, renal function benefits, and treatment safety. Results: Thirty-two patients were enrolled, with a median follow-up of 15 months. The majority of patients (26/32, 81.25%) were diagnosed with HER2-positive in biopsy-related IHC, including 3 cases of HER2 3+ and 23 cases of HER2 2+. During the follow-up, 17 local recurrences were observed in 10 patients and the 1-yr DFS rate was 68.75%. HER2 status was a significant predictive factor for local recurrence (OR, 0.15; 95% CI, 0.03, 0.91). Salvage RNU was performed in 2 patients, yielding a 1-yr CFS rate was 93.75%. The cCR rate is 78.13% (25/32). Postoperative renal function impairment was noted in 6 patients (18.75%). Mean eGFR improvements (ml/min/1.73m2) were observed with 3.15 at 1 month, 5.07 at 3 months, 2.41 at 6 months, and 3.97 at 12 months. Notably, no grade 3 or higher systemic toxicities were observed. Conclusions: Preliminary findings indicate that the combination of endoscopic Thulium laser ablation with perioperative systemic therapy (DV and ICIs) demonstrated promising efficacy and manageable safety in selected patients with localized high-risk UTUC. These results provide a solid foundation for the ongoing phase 2 trial (WUTSUP-03) and suggest a potential paradigm shift in the management of this challenging patient population.

COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint (CONFIDENCE) trial: Baseline clinical characteristics.

Finerenone, a selective nonsteroidal MRA, and SGLT2is both reduce CKD progression and improve kidney/CV outcomes. The CONFIDENCE study (NCT05254002; EudraCT 2021-003037-11) hypothesis is that early combination of finerenone and empagliflozin, a SGLT2i, is superior to either drug alone in reducing UACR over 6 months. CONFIDENCE is an ongoing, fully enrolled, randomized, controlled, double-blind, multicentre phase 2 clinical trial in adults (≥18 years of age) with CKD and T2D, eGFR of 30 to 90 ml/min/1.73 m2, and UACR of ≥100 to <5000 mg/g. Participants taking the clinically maximum tolerated dose of a renin-angiotensin system inhibitor for >1 month at screening were eligible. Participants were randomized 1:1:1 to once daily finerenone plus empagliflozin, finerenone plus placebo, or empagliflozin plus placebo; doses were 10 mg once daily for empagliflozin and 10 or 20 mg once daily for finerenone, depending on eGFR at baseline. Randomization was stratified by eGFR (< or ≥60 ml/min/1.73 m2) and UACR (≤ or >850 mg/g). The primary efficacy outcome is the relative change in UACR from baseline at Day 180. There were 818 participants randomized across 143 sites from 14 countries between July 2022 and August 2024. Mean eGFR (ml/min/1.73 m2 [SD]) was 54.2 (17.1). Median UACR (mg/g [IQR]) was 583 (292, 1140). Mean HbA1c (% [SD]) was 7.3 (1.2). Mean systolic/diastolic BP (mmHg) was 135.2/77.3. GLP-1 RAs and insulin were used by 182 (23%) and 313 (39%) participants, respectively. Atherosclerotic CV disease, diabetic retinopathy, and a history of heart failure were present in 223 (28%), 126 (16%), and 30 (4%) participants, respectively. The CONFIDENCE trial enrolled a diverse population with CKD and T2D and will determine the impact of simultaneous initiation of combination finerenone and a SGLT2i versus individual therapy on potentially mitigating the progression of CKD in people with T2D. Trial registration number: Clinicaltrials.gov NCT05254002; EudraCT 2021-003037-11.

Age-Related Changes in Brain Structure in Pediatric Chronic Kidney Disease

Pediatric patients with chronic kidney disease (CKD) exhibit reduced cerebellum volume, which is associated with neurocognitive deficits and a lower estimated glomerular filtration rate (eGFR), even before dialysis or transplantation. These differences have not been examined within the context of age-related brain changes during childhood to early adulthood. To evaluate differences in age-related neurodevelopmental changes in patients with CKD compared with control participants and to investigate associations between regional neuroanatomy, functional outcomes, and disease-related variables. Case-control study of individuals aged 6 through 21 years with and without CKD at an academic medical center in Iowa City, Iowa, from September 2016 to August 2024. Neurocognitive testing; 3-T magnetic resonance imaging. Participants completed standardized neurocognitive assessments and quantitative neuroanatomical scans. Brain regions of interest (ROIs) were analyzed for volumetric differences using automated pipelines. Multivariable linear models assessed neurocognitive and neuroanatomical differences between groups, including an age × group interaction for ROI analyses. The sample included 124 individuals (mean [SD] age, 12.8 [4.5] years; 74 [59.7%] male), including 87 control participants (44 [50.6%] male) and 37 participants with CKD (30 [81.1%] male). The mean (SD) eGFR was 71.3 [25.5] mL/min/1.73 m2 for the CKD group. Participants with CKD scored lower than control participants on most neurocognitive measures included in the analyses. The CKD group showed differential age-related changes in cerebellar gray matter (β = -0.10; 95% CI, -0.18 to -0.01; Cohen f = 0.22) and white matter (β = -0.09; 95% CI, -0.19 to -0.00; Cohen f = 0.19). The age × group interaction approached but did not reach significance for amygdala volume (β = 0.09; 95% CI, -0.01 to 0.19; Cohen f = 0.18; P = .06). Volumetric variation in these regions was associated with proxy ratings of executive function in patients with CKD. A significant, positive association between cerebellar gray matter and eGFR was observed in the CKD group (β = 0.04; 95% CI, 0.00 to 0.02; P = .01). In this case-control study, age-related neurodevelopmental differences were observed in pediatric patients with CKD compared with healthy peers. Reductions in cerebellar volume were associated with cognitive deficits and lower kidney function. These findings underscore the importance of monitoring neurodevelopmental trajectories in children with CKD, as early interventions may be necessary to mitigate cognitive impairments associated with CKD.

GFRs in Chinese CKD: A systematic review.

GFRs in Chinese CKD: A systematic review.

Randomized trial of dietary acid reduction and acid-base status of patients with CKD and normal eGFR

Randomized trial of dietary acid reduction and acid-base status of patients with CKD and normal eGFR

Dialysis Transition Patterns of Chronic Kidney Disease Patients With and Without Heart Failure.

Dialysis Transition Patterns of Chronic Kidney Disease Patients With and Without Heart Failure.

Kinetic estimated glomerular filtration rate and drug dosing in critically ill patients with acute kidney injury-A prospective observational study.

To study the impact of kinetic glomerular filtration rate (kGFR) on clinical decision making and its implications on drug dosing compared to that of estimated GFR (eGFR) using chronic kidney disease epidemiology collaboration (CKD-EPI) equation in critically ill patients with acute kidney injury (AKI) admitted in a tertiary level intensive care unit (ICU). Cross-sectional, prospective, observational study design. All patients admitted to Medical ICU, Fortis Hospital, Bangalore with AKI defined as per AKI network (AKIN) criteria. Patients were recruited after approval from the scientific and institutional ethics committee, with written informed consent. Serum creatinine values at admission and further values were noted. GFR was calculated using both formulas (CKD-EPI and kGFR) and documented at all intervals of creatinine sampling. Drugs requiring renal dose modification along with the dosing were documented. Sample size was calculated after a pilot study and a total of 107 patients were analyzed. Incidence of AKI was 12.84%. The mean (±SD) eGFR was 37.25 (±29.4) and kGFR was 42.5 (±33.2), (p-value .003). 70 (65.42%) patients required drug dose change when kGFR was used. Dosing changes from Day 1 to Day 5 are 53/104 (50.9%), 39/81 (48.1%), 12/26 (46.1%), 2/9 (28.5%), 1/2 (50%). Predominant dose changes were for antimicrobials: vancomycin (35.7%), acyclovir (23.1%), and meropenem (23%). Drug dosing using different methods of GFR calculation showed a difference in the dosing in 65.42% of patients with AKI. Accounting for change in creatinine over time using kinetic GFR may lead to better drug dosing in critically ill patients with AKI. Our study shows that calculating GFR using kGFR formula instead of CKD-EPI may change drug dosages among patients with AKI admitted in ICU. By replacing conventional GFR estimation formulas with kGFR we may reduce the drug dosing inaccuracies that are currently prevalent in this cohort of patients.

Nutritional Characterisation of Childhood Chronic Kidney Disease: Trace Element Malnutrition in Paediatric Renal Disease (TeMPeReD) Study.

In chronic kidney disease (CKD), poor nutrition is associated with poorer clinical outcomes. There are limited data on milder stages of childhood CKD. This study characterised the nutritional state of a cohort of children with CKD. Within the cohort (mean age 10.5 years, mean eGFR = 57 mL/min/1.73 m2), obesity defined by body mass index rates was comparable to that in the general population, but central obesity (waist-to-height ratio > 0.5) was evident in 44% of children. Although average nutrient intakes for the cohort were acceptable, there was marked variability in the risk of poor nutrient intake (<LRNI): selenium (35%), magnesium (35%), iodine (30%), and zinc (30%). No child met the recommended dietary fibre intake. The prevalence of frank deficiency of vitamins and minerals in blood concentrations was low. Blood concentrations of vitamins A and E were near-universally elevated. In those who had a decline in kidney function at the 12-month follow-up, dietary intake of fibre correlated with the degree of decline. Much work is needed to optimise the nutritional status of children with CKD as an important modifiable risk factor for disease progression and other important outcomes.

Recalibrating the kidney failure risk equation for a Mediterranean European population: reducing age and sex inequality.

Chronic kidney disease (CKD) patients may develop kidney failure (KF), receiving renal replacement therapy (RRT) in some cases. The Kidney Failure Risk Equation (KFRE-4), predicting RRT risk, is widely validated but not in a primary care Mediterranean European population. We aim to recalibrate KFRE-4 accordingly, considering death as a competing risk, to improve performance. Additionally, we recalibrate KFRE-4 for predicting KF, including all patients reaching CKD stage 5, not just those on RRT. Retrospective cohort study including individuals aged ≥50 years with confirmed glomerular filtration rate (eGFR) <60 mL/min/1.73m2 and measured albumin-to-creatinine ratio (ACR). Dataset was split into training and test sets. New KFRE-4 models were developed in the training set and performance was evaluated in the test set: Base hazard adapted-KFRE (Basic-RRT), Cox reestimation (Cox- RRT), Fine and Gray RRT reestimation (FG-RRT), and Fine and Gray KF reestimation (FG-KF). Among 165,371 primary care patients (58.1% female; mean age 78.1 years; mean eGFR 47.3 mL/min/1.73m2, median ACR 10.1 mg/g), original KFRE-4 showed good discrimination but poor calibration, overestimating RRT risk. Basic-RRT showed poorer performance. Cox-RRT and FG-RRT, enhancing the influence of old age and female sex, diminished overprediction. FG-RRT, considering death as a competing risk, resulted the best RRT model. Age and sex had less impact on KF prediction. A fully tailored recalibration model diminished RRT overprediction. Considering death as a competing event optimizes performance. Recalibrating for KF prediction offers a more inclusive approach in primary care, addressing the needs of women and elderly.

Evaluation of efficacy and safety of generic tacrolimus (Suprotac®) compared to reference tacrolimus (Prograf®) in kidney transplantation: a phase IV study.

Transplant recipients are given an immunosuppressive regimen such as tacrolimus to prevent organ rejection. Suprotac® is a generic tacrolimus that is utilized in kidney transplantation regimen in Iran. This post-market study was conducted to evaluate the safety and efficacy of Suprotac® in comparison with Prograf®. In this two-armed, open-label, parallel, active-controlled, and cohort study, de novo kidney transplant recipients aging 18 to 65 years were prescribed Suprotac® or Prograf® as part of the immunosuppressant protocol. The primary outcome was comparing the mean estimated glomerular filtration rate (eGFR) at month 12. The secondary outcomes were the assessment of patient and graft survival, acute rejections during hospitalization, tacrolimus dose, trough concentration, and trough concentration/dose (C/D) ratio, and adverse events (AEs) during the study period. A total of 201 patients were enrolled in this study. At discharge, the eGFR was lower in the Suprotac® group compared to the Prograf® group (51.70 ml/min/1.73m2 and 57.48 ml/min/1.73m2, respectively; p = 0.042). However, at month 12, there was no significant difference in mean eGFR between the two groups (58.94 ml/min/1.73m2 and 59.78 ml/min/1.73m2, respectively; p = 0.772). Other outcomes, including patient and graft survival, acute rejection during hospitalization, tacrolimus dose, trough concentration, and C/D ratio, and overall incidence of AEs were similar between the two groups (p > 0.05). The efficacy and safety profile of the generic tacrolimus were shown to be comparable to the reference tacrolimus at month 12.

The utility of split function testing in determining recovery of glomerular filtration rate after living kidney donation: a cohort study

BackgroundA number of UK transplantation centres use isotope studies to estimate the relative contribution from each kidney in living kidney donor assessment. The evidence that the estimation of pre-donation split function of the non-donated kidney influences post-donation renal recovery is limited. The aim of this study was to analyse whether, in the context of other donor factors, the split function of the non-donated kidney predicts the percentage recovery of glomerular filtration rate (GFR) at one-year post-donation.MethodologyA retrospective cohort analysis was undertaken on 291 living kidney donors in the Glasgow Renal and Transplant Unit between 1st January 2011 and 1st June 2022. Univariable and multivariable linear regression analysis was used to analyse the impact of donor factors on recovery of renal function at one year relative to baseline isotope GFR (iGFR) or to estimated GFR (eGFR by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula). Sub-analyses of donor outcome (% recovery of iGFR and eGFR at one year) were undertaken using single-measures ANOVA and grouping of donors by pre-donation isotope uptake of the non-donated kidney. ResultsMedian recovery of pre-donation GFR at 1 year was 70.0% (IQR 64.8-75.5). On linear regression analysis there was no significant association found between split function of the non-donated kidney and the percentage recovery of iGFR, although a small significant association was found for eGFR. There was no significant difference between mean iGFR or eGFR recovery on sub-analysis of donor outcomes.ConclusionsThis study demonstrated no clinically important predictive relationship between percentage recovery of renal function at 1 year after living kidney donation and pre-donation split function within the range accepted for donation in our centre.

Cardiovascular, kidney and safety outcomes with canagliflozin in older adults: A combined analysis from the CANVAS Program and CREDENCE trial.

SGLT2 inhibitors may be underused in older adults with type 2 diabetes due to concerns about safety and tolerability. This pooled analysis of the CANVAS Program and CREDENCE trial examined the efficacy and safety of canagliflozin according to age. Pooled individual participant data from the CANVAS Program (n = 10 142) and CREDENCE trial (n = 4401) were analysed by baseline age (<65 years, 65 to <75 years, and ≥75 years). A range of adjudicated clinical outcomes were assessed, including major adverse cardiovascular events and CKD progression, as well as safety outcomes. Cox proportional hazards models and Fine and Gray competing risk analysis were used. Among the 14 543 participants, 7927 (54.5%) were <65 years, 5281 (36.3%) were 65 to <75 years and 1335 (9.2%) were ≥75 years. Older participants had higher rates of atherosclerotic cardiovascular disease and heart failure, longer diabetes duration and lower mean eGFR. Reductions in cardiovascular and kidney outcomes with canagliflozin were consistent across age categories (all p trend >0.10), although there was some evidence that effects on cardiovascular death and all-cause death were attenuated with older age (p trend = 0.02 and 0.03, respectively). Although the incidence of adverse events increased with age, effects of canagliflozin on safety outcomes including acute kidney injury, volume depletion, urinary tract infections and hypoglycaemia, were not modified by age (all p trend >0.10). In patients with varying degrees of kidney function, canagliflozin reduced cardiovascular and kidney outcomes, regardless of age, with no additional safety concerns identified in older patients.