eGFR Threshold Research Articles

Hepatitis C infection and chronic kidney disease among Hispanics/Latinos.

Viral infections, including hepatitis C, can cause secondary glomerular nephropathies. Studies suggest that hepatitis C virus infection (HCV+) is a risk factor for chronic kidney disease (CKD) but evidence of this relationship is lacking among Hispanics/Latinos. We examined the association between HCV+ and incident CKD in a prospective cohort of Hispanics/Latinos enrolled in the Hispanic Community Health Study/Study of Latinos. HCV+ was defined by detectable HCV antibodies with additional confirmation through HCV RNA or recombinant immunoblot assay testing. Incident CKD was defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or sex-specific threshold for albuminuria measured during follow-up. We used Poisson regression to estimate incidence rate ratios (IRR) of CKD and changes in eGFR- or albuminuria-based risk stages, separately. We used linear regression to estimate associations with continuous, annualized changes in eGFR and albuminuria.Over a follow-up period of 5.9 years, 712 incident CKD events occurred among 10,430 participants. After adjustment for demographic characteristics and comorbidities, HCV+ was not associated with incident CKD, defined by eGFR and albuminuria thresholds (IRR 1.29, 95% Confidence Interval 0.61, 2.73). HCV+ was significantly associated with higher eGFR risk stages (IRR 2.39, 95% CI 1.47, 3.61) with most participants transitioning from stage G1 to G2. HCV+ was associated with a continuous, annualized eGFR decline of −0.69 mL/min/m2/year (95% CI −1.23, −0.16). This large, cohort study did not find evidence of a strong association between HCV+ and new-onset CKD among Hispanics/Latinos. HCV infection may not be associated with risk of CKD among Hispanics/Latinos, although treatment with direct-acting antivirals is recommended for all HCV+ individuals, including those with established CKD or end-stage kidney disease.

Evaluating the Impact and Rationale of Race-Specific Estimations of Kidney Function: Estimations from U.S. NHANES, 2015-2018.

BackgroundStandard equations for estimating glomerular filtration rate (eGFR) employ race multipliers, systematically inflating eGFR for Black patients. Such inflation is clinically significant because eGFR thresholds of 60, 30, and 20 ml/min/1.73m2 guide kidney disease management. Racialized adjustment of eGFR in Black Americans may thereby affect their clinical care. In this study, we analyze and extrapolate national data to assess potential impacts of the eGFR race adjustment on qualification for kidney disease diagnosis, nephrologist referral, and transplantation listing.MethodsUsing population-representative cross-sectional data from the United States National Health and Nutrition Examination Survey (NHANES) from 2015-2018, eGFR values for Black Americans were calculated using the Modification of Diet in Renal Disease (MDRD) equation with and without the 1.21 race-specific coefficient using cohort data on age, sex, race, and serum creatinine.FindingsWithout the MDRD eGFR race adjustment, 3.3 million (10.4%) more Black Americans would reach a diagnostic threshold for Stage 3 Chronic Kidney Disease, 300,000 (0.7%) more would qualify for beneficial nephrologist referral, and 31,000 (0.1%) more would become eligible for transplant evaluation and waitlist inclusion.InterpretationThese findings suggest eGFR race coefficients may contribute to racial differences in the management of kidney. We provide recommendations for addressing this issue at institutional and individual levels.FundingNo external funding was received for this study.

CKD Progression From the Time of Estimated GFR-Based Waitlist Eligibility and Racial Disparities in Transplant Access

Equations for estimated glomerular filtration rate (eGFR) that incorporate a term for race assign a higher value to Black individuals compared to non-Black individuals for the same sex, age, and serum creatinine concentration. This difference may contribute to racial disparities in kidney transplant access. We sought to (1) compare time from meeting a transplant eligibility threshold of eGFR≤20 mL/min/1.73 m2 to kidney failure with replacement therapy (KFRT) among Black, Hispanic, and White patients, and (2) assess the impact of incorporation of race into eGFR expressions on establishment of waitlist eligibility and time from eligibility to KFRT. Retrospective cohort. Using the OptumLabs Data Warehouse, we assembled a cohort of 40,042 White, 8,519 Black, and 3,569 Hispanic patients having at least one eGFR value between 20 and 60 mL/min/1.73 m2 within the preceding 2 years and an incident outpatient eGFR of≤20 mL/min/1.73 m2 between 2008-2018, using the CKD-EPI creatinine equation that includes a term for race coded as Black or non-Black. We then reassembled a Black patient cohort based on incident eGFR≤20 mL/min/1.73 m2 (n= 11,269) estimated using the same CKD-EPI equation but coding Black patients as non-Black. Race/ethnicity. Time to KFRT. Unadjusted and adjusted Fine-Gray models; linear regression to compute eGFR slopes. By 3 years, the cumulative incidence of KFRT was 20.5% among White patients, 40.9% among Hispanic patients, 36% among Black patients whose GFR was estimated using a race term coded as Black, and 28.7% among Black patients whose GFR was estimated using a race term coded as non-Black. In fully adjusted analyses including 11,269 Black patients with an eGFR≤20 mL/min/1.73 m2 based on coding them as non-Black, KFRT risk remained greater among Black (HR, 1.28 [95% CI, 1.15-1.43]) and Hispanic (HR, 1.66 [95% CI, 1.18-2.31]) patients than among White patients. Based on slopes of eGFR decline, coding Black patients as non-Black would allow earlier waitlist activation by an estimated median of 0.5 [interquartile range, 0.27-1.23] years. Inability to exclude individuals who would not be kidney transplant candidates if comprehensively evaluated. A uniform eGFR threshold provides less opportunity for being placed on the transplant waitlist among Black and Hispanic patients. For many Black patients, estimation of GFR as if their race category were non-Black would allow substantially earlier waitlisting but would not eliminate their shorter time to KFRT and reduced opportunity for preemptive transplantation compared with White patients.

Accounting for Age in the Definition of Chronic Kidney Disease

Using the same level of estimated glomerular filtration rate (eGFR) to define chronic kidney disease (CKD) regardless of patient age may classify many elderly people with a normal physiological age-related eGFR decline as having a disease. To compare the outcomes associated with CKD as defined by a fixed vs an age-adapted eGFR threshold. This population-based cohort study was conducted in Alberta, Canada and used linked administrative and laboratory data from adults with incident CKD from April 1, 2009, to March 31, 2017, defined by a sustained reduction in eGFR for longer than 3 months below a fixed or an age-adapted eGFR threshold. Non-CKD controls were defined as being 65 years or older with a sustained eGFR of 60 to 89 mL/min/1.73 m2 for longer than 3 months and normal/mild albuminuria. The follow-up ended on March 31, 2019. The data were analyzed from February to April 2020. A fixed eGFR threshold of 60 vs thresholds of 75, 60, and 45 mL/min/1.73 m2 for age younger than 40, 40 to 64, and 65 years or older, respectively. Competing risks of kidney failure (kidney replacement initiation or sustained eGFR <15 mL/min/1.73 m2 for >3 months) and death without kidney failure. The fixed and age-adapted CKD cohorts included 127 132 (69 546 women [54.7%], 57 586 men [45.3%]) and 81 209 adults (44 582 women [54.9%], 36 627 men [45.1%]), respectively (537 vs 343 new cases per 100 000 person-years). The fixed-threshold cohort had lower risks of kidney failure (1.7% vs 3.0% at 5 years) and death (21.9% vs 25.4%) than the age-adapted cohort. A total of 53 906 adults were included in both cohorts. Of the individuals included in the fixed-threshold cohort only (n = 72 703), 54 342 (75%) were 65 years or older and had baseline eGFR of 45 to 59 mL/min/1.73 m2 with normal/mild albuminuria. The 5-year risks of kidney failure and death among these elderly people were similar to those of non-CKD controls, with a risk of kidney failure of 0.12% or less in both groups across all age categories and a risk of death at 69, 122, 279, and 935 times higher than the risk of kidney failure for 65 to 69, 70 to 74, 75 to 79, and 80 years or older, respectively. This cohort study of adults with CKD suggests that the current criteria for CKD that use the same eGFR threshold for all ages may result in overestimation of the CKD burden in an aging population, overdiagnosis, and unnecessary interventions in many elderly people who have age-related loss of eGFR.

FC 067WHEN TO INITIATE DIALYSIS TO REDUCE MORTALITY AND CARDIOVASCULAR EVENTS IN ADVANCED CKD: A NATIONWIDE COHORT STUDY

Abstract Background and Aims There is currently no direct evidence to inform a specific glomerular filtration rate (GFR) to initiate maintenance dialysis. Previous studies are limited by the number of kidney function thresholds compared, immortal time or lead time biases, or small sample sizes. The only randomised trial (IDEAL) found no difference between early versus late start, but confidence intervals were wide. Method Nationwide observational cohort study using data from the Swedish Renal Registry between January 1, 2007 and December 31, 2016, with follow-up until June 1, 2017. Included individuals were receiving nephrologist care and had an eGFR between 10-20 ml/min/1.73m2. A randomized trial was emulated using the cloning, censoring and weighting method. Our primary analysis compared late (at an eGFR 5-7 ml/min/1.73m2 [eGFR5-7]), intermediate (eGFR7-10) and early (eGFR10-14) dialysis initiation to validate our analytical methods by comparison with IDEAL. Our secondary analysis compared fifteen dialysis initiation strategies with eGFR values ranging between 4 and 19 ml/min/1.73m2 in increments of 1 ml/min/1.73m2. Study outcomes were 5-year all-cause mortality and major adverse cardiovascular events (MACE; composite of cardiovascular death, non-fatal myocardial infarction and stroke). Adjusted hazard ratios [HR] and cumulative survival proportions were estimated using a dynamic marginal structural model. Results Among 10,290 individuals with advanced CKD (median age 73 years; 36% women; median eGFR 16.8 ml/min/1.73m2), 3725 individuals initiated dialysis, 4160 died and 2446 experienced MACE. In trial emulation, the 5-year mortality risk was 53.0% for eGFR5-7, 50.3% for eGFR7-10 and 49.7% for eGFR10-14. Compared with eGFR5-7, the 5-year absolute mortality risk difference was -2.7% (95% CI, -4.6% to -0.7%) for eGFR7-10 and -3.3% (95% CI, -5.2% to -1.3%) for eGFR10-14, with a HR of 0.97 (0.94-0.99) and 0.96 (0.94-0.99), respectively. The 5-year absolute MACE risk differences were -1.1% (95% CI, -3.8% to 2.1%) for eGFR7-10 and -3.6% (95% CI, -6.0% to -1.0%) for eGFR10-14 compared with eGFR5-7, with a HR of 1.00 (0.97-1.04) and 0.96 (0.97-1.00), respectively. When analysing fifteen eGFR thresholds, initiation at eGFR15-16 was associated with the largest reduction in mortality (absolute difference, -5.9% [95% CI, -8.0% to -3.1%]; HR, 0.88 [95% CI, 0.85-0.92]) and MACE (absolute difference, -4.5% [95% CI, -7.6% to -1.4%]; HR, 0.92 [95% CI, 0.89-0.97]), compared with eGFR4-5. This -5.9% absolute risk difference translates to a mean postponement of death of 1.8 months over 5-years of follow-up. However, dialysis would need to be initiated on average 14 months earlier. Conclusion Early dialysis initiation was associated with a modest reduction in mortality and cardiovascular events. Such a reduction may not outweigh the burden of longer dialysis treatment duration for the patient.

Elderly Patients in a Large Nephrology Unit: Who Are Our Old, Old-Old and Oldest-Old Patients?

The world population is aging, and the prevalence of chronic kidney disease (CKD) is increasing. Whether this increase is also due to the methods currently being used to assess kidney function in the elderly is still a matter of discussion. We aimed to describe the actual referral pattern of CKD patients in a large nephrology unit and test whether the use of different formulae to estimate kidney function could affect the staging and the need for specialist care in the older subset of our population. In 2019, 1992 patients were referred to our center. Almost 28% of the patients were aged ≥80 and about 6% were ≥90 years old. Among the causes of kidney disease, glomerulonephritis displayed a higher prevalence in younger patients whereas hypertensive or diabetic kidney disease were more prevalent in older patients. The prevalence of referred patients in advanced CKD stages increased with age; estimated glomerular filtration rate (eGFR) decreased with age regardless of which equation was used (chronic kidney disease epidemiology collaboration (CKD-EPI), Lund–Malmö Revised (LMR), modification of diet in renal disease (MDRD), Full Age Spectrum (FAS), or Berlin Initiative Study 1 (BIS)). With CKD-EPI as a reference, MDRD and FAS underestimated the CKD stage while LMR overestimated it. The BIS showed the highest heterogeneity. Considering an eGFR threshold limit of 45 mL/min for defining “significant” CKD in patients over 65 years of age, the variability in CKD staging was 10% no matter which equation was used. Our study quantified the weight of “old” and “old-old” patients on follow-up in a large nephrology outpatient unit and suggested that with the current referral pattern, the type of formula used does not affect the need for CKD care within the context of a relatively late referral, particularly in elderly patients.

Racial Disparities in Eligibility for Preemptive Waitlisting for Kidney Transplantation and Modification of eGFR Thresholds to Equalize Waitlist Time.

Patients may accrue wait time for kidney transplantation when their eGFR is ≤20 ml/min. However, Black patients have faster progression of their kidney disease compared with White patients, which may lead to disparities in accruable time on the kidney transplant waitlist before dialysis initiation. We compared differences in accruable wait time and transplant preparation by CKD-EPI estimating equations in Chronic Renal Insufficiency Cohort participants, on the basis of estimates of kidney function by creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys). We used Weibull accelerated failure time models to determine the association between race (non-Hispanic Black or non-Hispanic White) and time to ESKD from an eGFR of ≤20 ml/min per 1.73 m2. We then estimated how much higher the eGFR threshold for waitlisting would be required to achieve equity in accruable preemptive wait time for the two groups. By eGFRcr, 444 CRIC participants were eligible for waitlist registration, but the potential time between eGFR ≤20 ml/min per 1.73 m2 and ESKD was 32% shorter for Blacks versus Whites. By eGFRcys, 435 participants were eligible, and Blacks had 35% shorter potential wait time compared with Whites. By the eGFRcr-cys equation, 461 participants were eligible, and Blacks had a 31% shorter potential wait time than Whites. We estimated that registering Blacks on the waitlist as early as an eGFR of 24-25 ml/min per 1.73 m2 might improve racial equity in accruable wait time before ESKD onset. Policies allowing for waitlist registration at higher GFR levels for Black patients compared with White patients could theoretically attenuate disparities in accruable wait time and improve racial equity in transplant access.

Outcomes in Living Donor Kidney Transplantation: The Role of Donor’s Kidney Function

Introduction: Living donor kidney transplant (LDKT) is one of the best therapeutic options for end-stage kidney disease (ESKD). Guidelines identify different estimated glomerular filtration rate (eGFR) thresholds to determine the eligibility of donors. The aim of our study was to evaluate whether pretransplant donor eGFR was associated with kidney function in the recipient. Methods: We retrospectively studied LDKT recipients who received a kidney graft between September 1, 2005, and June 30, 2016 in the same transplant center in France and that had eGFR data available at 3, 12, 24, and 36 months posttransplant. Results: We studied 90 donor-recipient pairs. The average age at time of transplant was 51.47 ± 10.95 for donors and 43.04 ± 13.52 years for recipients. Donors’ average eGFR was 91.99 ± 15.37 mL/min/1.73 m2. Donor’s age and eGFR were significantly correlated (p < 0.0001, r2 0.023). Donor’s age and eGFR significantly correlated with recipient’s eGFR at 3, 12, and 24 months posttransplant (age: p < 0.001 at all intervals; eGFR p = 0.001, 0.003, and 0.016, respectively); at 36 months, only donor’s age significantly correlated with recipient’s eGFR. BMI, gender match, and year of kidney transplant did not correlate with graft function. In the multivariable analyses, donor’s eGFR and donor’s age were found to be associated with graft function; correlation with eGFR was lost at 36 months; and donor’s age retained a strong correlation with graft function at all intervals (p < 0.001). Conclusions: Donor’s eGFR and age are strong predictors of recipient’s kidney function at 3 years. We suggest that donor’s eGFR should be clinically balanced with other determinants of kidney function and in particular with age.

Phase-3 Randomized Controlled Trials on Exclusion of Participants With Kidney Disease in COVID-19

Phase-3 Randomized Controlled Trials on Exclusion of Participants With Kidney Disease in COVID-19

The prevalence of chronic kidney disease in Iceland according to KDIGO criteria and age-adapted estimated glomerular filtration rate thresholds

Most epidemiological studies on chronic kidney disease (CKD) are based solely on estimated glomerular filtration rate (eGFR). Few studies have included proteinuria, while the chronicity criterion is usually omitted. To explore this, we examined the prevalence of CKD stages 1-5 in Iceland based on multiple markers of kidney damage. All serum creatinine values, urine protein measurements and diagnostic codes for kidney diseases and comorbid conditions for people aged 18 years and older were obtained from electronic medical records of all healthcare institutions in Iceland in 2008-2016. CKD was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline using diagnoses indicative of a chronic kidney disease, proteinuria and/or an eGFR under 60 mL/min/1.73 m2 for over three months. Mean annual age-standardized prevalence of CKD stages 1-5 was calculated based on the KDIGO criteria and age-adapted eGFR thresholds from 2,120,147 creatinine values for 218,437 individuals, 306,531 proteinuria measurements for 86,364 individuals and 6973 individuals carrying a kidney disease diagnosis. Median age was 63 years (range, 18-106) and 47% were male. The mean annual age standardized CKD prevalence was 5.13% for men and 6.75% for women using the KDIGO criteria but by age-adapted eGFR cut-offs, the prevalence was 3.27% for men and 4.01% for women. Thus, our nationwide study, defining CKD in Iceland with strict adherence to the KDIGO criteria, demonstrates a lower prevalence of CKD than anticipated from most previous studies.

Improved nephrology referral of chronic kidney disease patients: potential role of smartphone apps.

In chronic kidney disease (CKD), referral to nephrology is based on Kidney Disease: Improving Global Outcomes 2012 guidelines and is generally indicated when the estimated glomerular filtration rate (eGFR) is <30 mL/min/1.73 m2 or when there is a rapid decline of eGFR, elevated urinary albumin:creatinine ratio (>300 mg/g) or other ‘alert’ signs such as the presence of urinary red blood cell casts. Since eGFR declines with ageing in otherwise healthy individuals, we propose that the eGFR threshold for nephrology referral should be adjusted according to age. According to current recommendations, young patients without rapidly progressing CKD are referred more often to nephrology when CKD is more severe, compared with age-matched controls with normal eGFRs, than elderly CKD patients. In this commentary, we discuss the age factor and other specific situations not considered in current guidelines for nephrology referral of CKD patients.

Modification of eGFR-Based CKD Definitions: Perfect, or Enemy of the Good?

Modification of eGFR-Based CKD Definitions: Perfect, or Enemy of the Good?

Starting Renal Replacement Therapy: Is It About Time?

Background: Studies of the timing of end-stage renal disease (ESRD) have primarily defined “early” versus “late” initiation of dialysis using estimated glomerular filtration rate (eGFR)-based criteria. Our objective was to determine the theoretical time that could be spent in chronic kidney disease (CKD) stage 5 prior to reaching a conservative eGFR threshold of 5 mL/min/1.73 m² compared to the actual time spent in CKD stage 5 by risk factors of interest. Methods: Eight-hundred and seventy Chronic Renal Insufficiency Cohort participants with CKD stage 5 who started renal replacement therapy (RRT) were included for retrospective study. We used mixed models to estimate the person-specific trajectory of renal function. We then used these individual trajectories to estimate the amount of time that would be spent in CKD stage 5 (between eGFR of 15 and 5 mL/min/1.73 m²) and compared this estimate to the actual time spent in CKD stage 5 prior to ESRD (between eGFR of 15 mL/min/1.73 m² and ESRD). Results: We found the median observed time between eGFR of 15 mL/min/1.73 m² to RRT was 9.6 months, but the median predicted time between eGFR of 15 mL/min/1.73 m² to eGFR of 5 mL/min/1.73 m² was 17.7 months. Some of the largest differences between the predicted and actual amount of time spent in CKD stage 5 were noted among those with systolic blood pressure <140 mm Hg (9.7 months longer predicted compared to actual), proteinuria <1 g/g (9.1 months), and serum albumin ≥3.5 g/dL (9.0 months). Conclusion: We found marked differences between the actual and predicted time spent in CKD stage 5 based on risk factors of interest. We believe that placing timing of dialysis initiation in the perspective of time is novel and may identify subgroups of patients who may derive particular benefit from a more concerted effort to delay RRT.

Chronic Kidney Disease and Kidney Cancer Surgery: New Perspectives.

We sought to provide a contemporary understanding of chronic kidney disease and its relevance to kidney cancer surgery. Another purpose was to resolve points of discrepancy regarding the survival benefits of partial vs radical nephrectomy by critically evaluating the results of prospective and retrospective studies in the urological literature. We performed a comprehensive literature search for relevant articles listed in MEDLINE® from 2002 to 2018 using the key words radical nephrectomy, partial nephrectomy, glomerular filtration rate, kidney function and chronic kidney disease. We also assessed select review articles and society guidelines about chronic kidney disease pertinent to urology and nephrology. Complete evaluation of the potential consequences of chronic kidney disease involves assessment of the cause, the glomerular filtration rate level and the degree of albuminuria. Chronic kidney disease is commonly defined in the urological literature solely as a glomerular filtration rate less than 60 ml/minute/1.73 m2. This ignores the significance of the cause of chronic kidney disease, and the presence and degree of albuminuria. Although this glomerular filtration rate is relevant for preoperative assessment of patients who undergo surgery of kidney tumors, recent studies suggest that a glomerular filtration rate less than 45 ml/minute/1.73 m2 represents a more discerning postoperative prognostic threshold. Reported survival benefits of partial over radical nephrectomy in retrospective studies were likely influenced by selection bias. The lack of survival benefit in the partial nephrectomy cohort in the only randomized trial of partial vs radical nephrectomy was consistent with data demonstrating that patients in each study arm were at relatively low risk for mortality due to chronic kidney disease when accounting for the chronic kidney disease etiology and the postoperative glomerular filtration rate. The prognostic risk of chronic kidney disease in patients with kidney cancer is increased when the preoperative glomerular filtration rate is less than 60 ml/minute/1.73 m2 or the postoperative rate is less than 45 ml/minute/1.73 m2. Additional factors, including nonsurgical causes of chronic kidney disease and the degree of albuminuria, can also dramatically alter the consequences of chronic kidney disease after kidney cancer surgery. Urologists must have a comprehensive knowledge of chronic kidney disease to assess the risks and benefits of partial vs radical nephrectomy when managing tumors with increased complexity and/or oncologic aggressiveness.

Utility of the HAS-BLED score for risk stratification of patients with acute coronary syndrome.

HAS-BLED score was developed for bleeding prediction in patients with atrial fibrillation (AF). Recently, it was also used in patients undergoing percutaneous coronary interventions (PCI). This study analyzes the HAS-BLED predictivity for bleedings and mortality in patients with acute coronary syndromes (ACS) without AF, and evaluates the utilization of alternative criteria for renal dysfunction. The study population was composed of 704 patients with ACS. Six-hundred and eleven patients completed the follow-up. The HAS-BLED score was calculated both using the original definition of renal dysfunction, both using three alternative eGFR thresholds (< 30, < 60 and ≤ 90ml/min/1.73 mq). In-hospital and post-discharge bleedings and mortality were recorded, and calibration and discrimination of the various risk models were evaluated using the Hosmer-Lemeshow test and the C-statistic. In-hospital bleedings were 4.7% and mortality was 2.7%. Post-discharge bleedings were 3.1% and mortality was 4.4%. Regarding bleeding events and in-hospital mortality, the HAS-BLED original risk model demonstrated a moderate-to-good discriminative performance (C-statistics from 0.65 to 0.76). No significant differences were found in predictive accuracy when applying alternative definitions of renal dysfunction based on eGFR, with the exception of post-discharge mortality, for which HAS-BLED model assuming an eGFR value < 60ml/min/1.73 mq showed a discriminative performance significantly higher in comparison to the other risk models (C-statistic 0.71 versus 0.64-0.66). In conclusion, in our ACS population, the HAS-BLED risk score showed a fairly good predictive accuracy regarding in-hospital and follow-up bleeding events and in-hospital mortality. The use of renal dysfunction alternative criteria based on eGFR values resulted in out-of hospital mortality predictive accuracy enhancement.

An investigation into the accuracy of using serum creatinine estimated glomerular filtration rate to predict measured glomerular filtration rate.

The aim of the study was to identify a threshold value of the estimated glomerular filtration rate (eGFR) that would predict a measured glomerular filtration rate (mGFR) of ≤25 ml/min/1.73 m. This is to guide use of the new British Nuclear Medicine Society guidelines, which specifies a 24 h sample for patients with a GFR of ≤25 ml/min/1.73 m, when using the single-sample (SS) method. Data from 1956 patient studies were used to calculate values for the GFR using the slope intercept (SI) method and SS , which was taken 210 min after injection. A sub-data set of 241 patients was taken with patients having an mGFR of ≤80 ml/min/1.73 m by the SS or SI method and an eGFR value within 28 days of the mGFR. The Modification of Diet in Renal Disease equation was used to calculate the eGFR. Receiver operator characteristic curves comparing the sensitivity and specificity of using the eGFR to predict values of the mGFR were used to find a threshold value for the eGFR. There is a large variation in the accuracy of using the eGFR to predict the mGFR value. The mean difference for the SI method is -2%, with an absolute percentage difference of 22% and a range of -121 to 63%. The SS method has a mean percentage difference of -1%, absolute percentage difference of 23% and a range of -153 to 86%.From the receiver operator characteristic graphs, an eGFR value of 40 ml/min/1.73 m was chosen to maximise the sensitivity of the eGFR threshold value used to predict an mGFR value of ≤25 ml/min/1.73 m. The eGFR value has a high error when used for predicting the mGFR. Therefore, the study recommends that an eGFR threshold value of ≤40 ml/min/1.73 m is used to predict mGFRs of ≤25 ml/min/1.73 m in order to optimise the likelihood of identifying all such patients.

Effects of deferasirox dose and decreasing serum ferritin concentrations on kidney function in paediatric patients: an analysis of clinical laboratory data from pooled clinical studies

Serious and fatal deferasirox-induced kidney injury has been reported in paediatric patients. This study aimed to investigate the effects of deferasirox dose and serum ferritin concentrations on kidney function and the effect of impaired kidney function on dose-normalised deferasirox minimum plasma concentration (Cmin). We did a case-control analysis using pooled data from ten clinical studies. We identified transfusion-dependent patients with thalassaemia, aged 2-15 years, who were receiving deferasirox and had available baseline and follow-up serum creatinine and ferritin measurements. Cases of acute kidney injury (AKI) were defined according to an estimated glomerular filtration rate (eGFR) threshold of 90 mL/min per 1·73 m2 or less (if baseline eGFR was ≥100 mL/min per 1·73 m2), an eGFR of 60 mL/min per 1·73 m2 or less (if baseline eGFR was <100 mL/min per 1·73 m2), or an eGFR decrease from baseline of at least 25%. Cases were matched to control visits (eGFR ≥120 mL/min per 1·73 m2) on age, sex, study site, and time since drug initiation. We calculated rate ratios for AKI using conditional logistic regression, and evaluated the effect of eGFR changes on Cmin. Among 1213 deferasirox-treated paediatric patients, 162 cases of AKI and 621 matched control visits were identified. Patients with AKI had a mean 50·2% (SD 15·5) decrease in eGFR from baseline, compared with a 6·9% (29·8) decrease in controls. A significantly increased risk for AKI (rate ratio 1·26, 95% CI 1·08-1·48, p=0·00418) was observed per 5 mg/kg per day increase in deferasirox dispersible tablet dose (equivalent to a 3·5 mg/kg per day dose of film-coated tablets or granules), above the typical starting dose (20 mg/kg per day). An increased risk (1·25, 1·01-1·56, p=0·0400) for AKI was also observed per 250 μg/L decrease in serum ferritin, starting from 1250 μg/L. High-dose deferasirox (dispersible tablet dose >30 mg/kg per day) resulted in an increased risk (4·47, 1·25-15·95, p=0·0209) for AKI when serum ferritin was less than 1000 μg/L. Decreases in eGFR were associated with increased Cmin. Deferasirox can cause AKI in a dose-dependent manner. The increased AKI risk with high-dose deferasirox and lower serum ferritin concentration is consistent with overchelation as a causative factor. Small decreases in eGFR correlate with increased deferasirox Cmin, especially in younger patients. Physicians should closely monitor renal function and serum ferritin, use the lowest effective dose to maintain acceptable body iron burden, and interrupt deferasirox treatment when AKI or volume depletion are suspected. None.

Association between hearing organ and renal function in young adult type 1 diabetic patients: A cross-sectional study

Type 1 diabetes can lead to impaired function of many organs and tissues. The aim of this study was to evaluate associations between hearing and kidney function in young adult type 1 diabetic patients. 31 patients (9 women) with type 1 diabetes, aged <45, with disease duration <10 years were included. Blood and urine samples for laboratory tests and urinary albumin excretion (UAE) assessment were obtained. eGFR was calculated with CKD-EPI formula. In all patients pure-tone audiometry, transient evoked otoacoustic emissions and auditory brainstem responses were evaluated, also eye fundus was examined. Mean patients’ age was 29.5 ± 7.0 years and disease duration 4.6 ± 2.6 years. All patients had eGFR > 60.0 ml/min/1.73 m2. In one case microalbuminuria and in 3 patients early retinopathy were revealed. Linear correlation between eGFR and hearing threshold at 4, 6, 8 and 12 kHz was found. Patients with hearing impairment (n = 7) had lower eGFR 108.8 vs. 121.7 ml/min/1.73 m2, p = 0.047 compared to normal-hearing subjects. Also patients with absence of otoacoustic emissions in at least one ear had lower eGFR, 103.1 vs. 123.3 ml/min/1.73 m2, p < 0.001, compared to the remaining group. In auditory brainstem responses we found significant linear correlation between eGFR and wave III and interval I-III latencies, and between UAE and waves III, V and interval I-III latencies. This study suggests existence of relationship between hearing and kidney function in type 1 diabetic patients. Pathways directly linking hearing and renal function are unknown. Larger studies are necessary to further analyze these relationships.

Predicting survival of older community-dwelling individuals according to five estimated glomerular filtration rate equations: The InChianti study.

There is uncertainty about which estimated glomerular filtration rate eGFR equation to use in older people with respect to the prediction of prognosis. Our aim was: (i) to compare the discriminative capacity of eGFR estimated by different equations with respect to all-cause mortality; and (ii) to identify the eGFR threshold at which the risk of mortality starts to increase for each equation. We used data from 828 community-dwelling older adults aged >65 years enrolled in the InCHIANTI study. The outcome measure was all-cause mortality at 9 years. GFR was estimated by five different equations: Chronic Kidney Disease Epidemiological Collaboration (creatinine equation [CKD-EPIcre ], and creatinine and cystatin C equation [CKD-EPIcre-cys ]), Berlin Initiative Study (BIScre and BIScre-cys ) and full age spectrum. Sensitivity, specificity, areas under receiver operating curve (AUC) and C-statistics were used to compare their predictive capacity. The best mix of sensitivity, specificity, AUC and C-statistic value in predicting mortality was observed with BIS equations. BIScre (AUC 0.65, 95% CI 0.61-0.69) outperformed both CKD-EPIcre (AUC 0.60, 95% CI 0.56-0.64; P = 0.005) and full age spectrum (AUC 0.63, 95% CI 0.59-0.67; P = 0.002) in terms of predictivity. Similarly, BIScre-cys (AUC 0.67, 95% CI 0.63-0.71) outperformed CKD-EPIcre-cys (AUC 0.63, 95% CI 0.59-0.67; P = 0.01). AUC obtained with equations also including cystatin C were not significantly different compared with their creatinine-based counterparts. The risk of long-term mortality began to increase at under 65.6 mL/min/1.73 m2 for CKD-EPIcre-cys , 60.5 for CKD-EPIcre , 60 for BIScre-cys , 56.3 for BIScre and 55.2 for full age spectrum. The BIS equation discriminates the risk of all-cause mortality better than other equations in older community-dwelling individuals. The eGFR threshold under which mortality starts to increase could change as a function of the equation used. Geriatr Gerontol Int 2018; 18: 607-614.

Is Chronic Dialysis the Right Hard Renal End Point To Evaluate Renoprotective Drug Effects?

RRT and doubling of serum creatinine are considered the objective hard end points in nephrology intervention trials. Because both are assumed to reflect changes in the filtration capacity of the kidney, drug effects, if present, are attributed to kidney protection. However, decisions to start RRT are not only on the basis of filtration capacity of the kidney, but also on other factors. We therefore compared the time to RRT with the time to a fixed eGFR threshold and assessed the effect of the renoprotective drug irbesartan on both components. Post hoc analysis of two clinical trials, the Irbesartan Diabetic Nephropathy Trial (IDNT) and Reduction of End points in Non-insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan Trial, in patients with type 2 diabetes and nephropathy. The time to a predefined eGFR level of 11 ml/min per 1.73 m2 (eGFR11), calculated by within-patient linear regression, was compared with the time to RRT or sustained serum creatinine ≥6 mg/dl. A large difference was observed in the median time to RRT (779 days) compared with eGFR11 (678 days; P=0.01). We also observed a large variation in the difference between the time to RRT and eGFR11. In IDNT, the hazard ratio for the effect of irbesartan on the serum creatinine ≥6.0 mg/dl end point was 0.60 (95% confidence interval, 0.39 to 0.91; P=0.02), whereas it was smaller for the RRT end point (hazard ratio, 0.78; 95% confidence interval, 0.58 to 1.07; P=0.12). This study shows a difference in the time to RRT and a fixed eGFR threshold, and shows that the effect of an angiotensin receptor blocker on a filtration-based end point versus RRT varies. This implies that evaluating renoprotective effects of drugs with a combined RRT and doubling of serum creatinine end point may result in evaluating other effects beyond renoprotection alone. Future trials should consider registering all parameters that lead to RRT decisions.