Greater Decline In eGFR Research Articles

Kidney growth progression patterns in autosomal dominant polycystic kidney disease

BackgroundPrognosis for autosomal dominant polycystic kidney disease (ADPKD), the main inherited cause of kidney failure, relies on estimating cystic growth using linear formulas derived from height-adjusted total kidney volume (Ht-TKV). However, nonlinear renal growth patterns may occur in typical ADPKD. AimsTo determine kidney outcomes of subjects diagnosed with typical ADPKD exhibiting nonlinear, and unpredictable cystic growth during follow-up. MethodsRetrospective cohort study. We categorized TKV changes in individuals with typical ADPKD according to observed kidney growth trajectories. Ht-TKV was calculated from consecutive CT or MRI using the ellipsoid method. We compared estimated glomerular filtration rate (eGFR) trajectories with linear mixed models. ResultsWe included 83 individuals with ADPKD (67% women; age 47 ± 12 years; follow-up 5.2 years [IQR 2.8–9.0]). Three kidney growth patterns were observed: slow progression (24%, <3%/year linear increase), fast progression (39%, ≥3%/year linear increase), and atypical progression (37%, nonlinear growth). Adjusted ht-TKV change in mL/m/year was +1.4 (IQR –4.5 to +10.0), +40.3 (+16.9 to +89.3), and +32.8 (+15.9 to +85.9) for slow, fast, and atypical progressors, respectively (p <0.001). Atypical progressors exhibited a significantly greater decline in eGFR in mL/min/m²/year (–7.9, 95% CI –6.5, –3.9) compared to slow (–0.5, 95% CI –3.1 to +0.5) and fast progressors (–3.4, 95% CI –7.9, –2.0; between-group p <0.001). Atypical progressors had a higher proportion of acute complications, including hemorrhages, infections, and urolithiasis (84%), compared to slow (20%) and fast progressors (31%) (p <0.001). ConclusionIn typical ADPKD, nonlinear, abrupt, and unpredictable cyst growth occurs frequently, leading to a higher risk of acute complications and kidney function decline.

Tubular biomarkers in proteinuric kidney disease: histology correlation and kidney prognosis of tubular biomarkers.

Proteinuria is not only a biomarker of chronic kidney disease (CKD) but also a driver of CKD progression. The aim of this study was to evaluate serum and urinary tubular biomarkers in patients with biopsied proteinuric kidney disease and to correlate them with histology and kidney outcomes. A single-center retrospective study was conducted on a cohort of 156 patients from January 2016 to December 2021. The following urinary and serum biomarkers were analyzed on the day of kidney biopsy: beta 2 microglobulin (β2-mcg), alpha 1 microglobulin (α1-mcg), neutrophil gelatinase-associated lipocalin (NGAL), urinary kidney injury molecule-1 (uKIM-1), monocyte chemoattractant protein-1 (MCP-1), urinary Dickkopf-3 (uDKK3), uromodulin (urinary uUMOD), serum kidney injury molecule-1 (sKIM-1) and serum uromodulin (sUMOD). A composite outcome of kidney progression or death was recorded during a median follow-up period of 26 months. Multivariate regression analysis identified sUMOD (β-0.357, P<.001) and uDKK3 (β 0.483, P<.001) as independent predictors of interstitial fibrosis, adjusted for age, estimated glomerular filtration rate (eGFR) and log proteinuria. Elevated levels of MCP-1 [odds ratio 15.61, 95% confidence interval (CI) 3.52-69.20] were associated with a higher risk of cortical interstitial inflammation >10% adjusted for eGFR, log proteinuria and microhematuria. Upper tertiles of uDKK3 were associated with greater eGFR decline during follow-up. Although not a predictor of the composite outcome, doubling of uDKK3 was a predictor of kidney events (hazard ratio 2.26, 95% CI 1.04-4.94) after adjustment for interstitial fibrosis, eGFR and proteinuria. Tubular markers may have prognostic value in proteinuric kidney disease, correlating with specific histologic parameters and identifying cases at higher risk of CKD progression.

Abstract P417: A Cumulative Score Approach to Evaluating the Impact of Five Modifiable Lifestyle Factors on Kidney Function

Background: Data from the Gubbio population study were used to investigate the impact of a cumulative score combining physical activity, intake of alcohol, sodium, potassium and protein on the decline of kidney function. Methods: The Gubbio Study is a longitudinal study on the population of Gubbio, a town in central Italy; it started in the year 1983, and addressed the resident population aged 5 +. Three exams were performed: Exam 1 (baseline) Exam 2 (6-year follow-up) and Exam 3 (20-year follow-up); this analysis is on the 3,039 adult individuals (Age 18+ at baseline) who participated in Exam 2 (1989-92) and Exam 3 (2001-07). Kidney function was estimated as glomerular filtration rate (eGFR) with the CKD-Epi equation (mL/min x 1.73 m 2 ). Habitual physical activity and alcohol intake were assessed by standard questionnaires. Dietary intake of protein, sodium and potassium were measured by urinary markers. Each factor received score 0 for the tertile associated with greater eGFR decline, score 1 for the tertile associated with intermediate decline and score 2 for the tertile associated with greater decline. A cumulative score (CS) was then calculated for each individual and used as main independent variable. Results: After correction to avoid low-n bias, the CS ranged from 1 (low risk for all factors) to 9 (high risk for all factors). The mean was 5+/-2, with skewness = 0.016. Multiple linear regression showed a relation with the annualized decline in eGFR (slope = - 0,027, 95% CI = - 0.039/ - 0.014, p &lt; 0.001). Incidence of low eGFR was higher in the groups with higher CS, ranging from 2% in the group with CS = 1 to 12.9% in the group with CS = 9. Multivariate logistic regression analysis confirmed the correlation (p &lt; 0.001). Conclusion: These data indicate a significant independent association between a score comprising five modifiable lifestyle factors and the long-term decline of kidney function, providing a tool for the quantification of its impact on the long-term incidence of low eGFR.

Deterioration of Kidney Function Is Affected by Central Arterial Stiffness in Late Life.

Cardiovascular diseases affect kidney function. The aim of this study was to investigate the possible associations between hemodynamic parameters and change in kidney function in individuals aged 75 years and older. Data on hemodynamics and blood and urine samples were collected at baseline and during one-year visits. Hemodynamics were split into two groups based on median values. Changes in the estimated glomerular filtration rate (eGFR) were investigated between low and high groups for each hemodynamic parameter using analysis of variance. Changes in the albumin-creatinine ratio (ACR) were examined as binary outcomes (large increase vs. stable) using logistic regression. The population consisted of 252 participants. Participants in the high central systolic blood pressure (cSBP) group had a greater decline in eGFR than participants in the low cSBP group (-6.3% vs. -2.7%, p = 0.006). Participants in the high aortic pulse wave velocity (aPWV) group had a greater decline in eGFR than those in the low aPWV group (-6.8% vs. -2.5%, p = 0.001). Other hemodynamic parameters were not associated with eGFR changes. Hemodynamics were not associated with changes in the ACR; aPWV and cSBP appear to be predictors for eGFR decline in older age; monitoring and treatment of elevated stiffness might be helpful in order to prevent kidney function decline.

Prevalence of mycophenolate mofetil discontinuation and subsequent outcomes in pediatric kidney transplant recipients: A PNRC study.

Mycophenolate Mofetil (MMF) is an effective immunosuppressant used in kidney transplant recipients to prevent acute rejection. Complications such as diarrhea, leukopenia, and infections may necessitate the reduction or discontinuation of MMF. The objective of the study was to investigate the prevalence, timing, and reasons for MMF discontinuation and its association with outcomes in pediatric kidney transplant recipients. Seven Pediatric Nephrology Research Consortium (PNRC) centers participated in a retrospective analysis of kidney transplant recipients <21 years of age. Characteristics and outcomes of patients in whom MMF was discontinued were compared to those who continued taking MMF throughout the first 2 years post-transplant. The study population included 288 participants (mean age 11.2 years) from 7 North American transplant centers. MMF was discontinued in 93/288 (32%) of participants. Common reasons for discontinuation included infections (35%), diarrhea (32%), leukopenia (15%), and others (18%). Increased cumulative alloimmunity (55% vs. 42%, p = .02), increased number of hospitalizations (82% vs. 67%, p = .01), and viral replications (79% vs. 47%, p < .0001) were observed in the MMF discontinuation group compared to the continuation group. Greater eGFR decline also occurred in the MMF discontinuation group over 2 years of follow-up (-7 vs. -1 mL/min/1.73 m2 , p = .05). Almost a third of pediatric kidney transplant recipients who begin MMF for maintenance immunosuppression have it discontinued within the first 2 years post-transplant, and this subset of patients is more likely to experience adverse outcomes. New strategies are needed to manage MMF therapy and improve post-transplant outcomes.

Diet and Other Modifiable Factors in Long-Term Decline of Kidney Function: Observational and Population-Based Cohort Study.

Lower physical activity, lower alcohol intake, higher protein intake, higher sodium intake, and lower potassium intake related to greater kidney function decline over time, according to previous studies. The present study aimed to analyze the cumulative effects of these factors. This prospective, observational, population-based cohort study included 3039 adult examinees of the Gubbio study who participated in the baseline exam and 15-year follow-up exam. Kidney function was evaluated as estimated glomerular filtration rate (eGFR). Habitual physical activity in leisure time and habitual alcohol intake were assessed by questionnaires; dietary intakes of protein, sodium, and potassium were assessed by urinary markers. Based on previous reports, each one of the five modifiable factors was scored 0 for the tertile associated with smaller eGFR decline (low risk), 2 for the tertile associated with greater eGFR decline (high risk), and 1 for the intermediate tertile (intermediate risk). A cumulative score was calculated as the sum of the factor-specific scores and used as the main independent variable. The cumulative score ranged from 0 to 10, that is, from low risk for all factors to high risk for all factors (skewness = 0.032, mean ± SD = 5 ± 2). To avoid the bias of low-n analyses, score 0 was re-coded as 1 and score 10 was recoded as 9; after re-coding, the cumulative score ranged from 1 to 9 (skewness = 0.016, mean ± SD = 5 ± 2). The cumulative score related to annualized eGFR change in multi-variable linear regression (slope = -0.027, 95%CI = -0.039/-0.014, p < 0.001); findings were consistent in apparently healthy examinees and other subgroups. De novo incidence of eGFR < 60 mL/min × 1.73 m2 was higher along the cumulative score (p < 0.001). Compared to score 1 (n examinees = 35, adjusted incidence = 2.0%), incidence of low kidney function was 4.5 times higher in score 5 (n examinees = 624, adjusted incidence = 8.9%) and 6.5 times higher in score 9 (n examinees = 86, adjusted incidence = 12.9%). The cumulative score related to incidence of low kidney function in multi-variable logistic regression (odds ratio = 1.19, 95%CI = 1.08/1.32, p < 0.001). The combination of five modifiable factors predicted large differences in long-term incidence of low kidney function.

Long-Term Change in Renal Function After Intravitreal Anti-VEGF Treatment for Diabetic Macular Edema: A 2-Year Retrospective Cohort Study.

To investigate the longitudinal changes in renal function and associated factors after intravitreal anti-vascular endothelial growth factor (VEGF) administration in diabetic macular edema (DME). A total of 108 patients who had received intravitreal ranibizumab or aflibercept for DME and had follow-up visits for at least 2years in one hospital were retrospectively enrolled. The estimated glomerular filtration rate (eGFR) at baseline and during the follow-up period and receipt of any renal replacement therapy were recorded. Linear regression and Cox regression models were used to evaluate factors associated with eGFR decline and renal replacement therapy. After intravitreal anti-VEGF treatment, eGFR showed a mean decline of -10.4 ± 23.2% and -16.5 ± 26.4% at months 12 and 24, respectively. Patients in the eGFR > 120mL/min and 15-30mL/min groups had the greatest decline (-32.0 ± 20.6% and -37.4 ± 30.9%, respectively) while those in the 61-90mL/min group had the smallest decline (-4.3 ± 19.7%) in eGFR after the 2-year treatment. One out of 52 patients (1.9%) receiving ranibizumab and five out of 56 patients (8.9%) receiving aflibercept started hemodialysis or peritoneal dialysis within the 2-year follow-up period (P = 0.21). Baseline eGFR correlated with renal replacement therapy after intravitreal anti-VEGF treatment (hazard ratio = 0.879 per increase of 1 in eGFR, P = 0.018). In DME patients receiving intravitreal anti-VEGF treatment, a persistent decline in eGFR was observed during the 2-year treatment course. Patients with extremely high or low eGFR had greater eGFR decline, and those with poor baseline eGFR tended to require dialysis after intravitreal anti-VEGF treatment.

The urine-to-plasma urea concentration ratio is associated with eGFR and eGFR decline over time in a population cohort.

Evaluation of renal function and of factors associated with its decline are important public health issues. Besides markers of glomerular function [e.g. glomerular filtration rate (GFR)], those of tubular functions are rarely evaluated. Urea, the most abundant urinary solute, is markedly concentrated in urine when compared with plasma. We explored the urine-to-plasma ratio of urea concentrations (U/P urea ratio) as a marker of tubular functions. We evaluated the relationship of the U/P urea ratio with eGFR at baseline in 1043 participants (48±17 years) from the Swiss Kidney Project on Genes in Hypertension (SKIPOGH) population-based cohort, using mixed regression. In 898 participants, we assessed the relation between U/P urea ratio and renal function decline between two study waves 3 years apart. We studied U/P ratios for osmolarity, Na, K and uric acid for comparison. In a transversal study at baseline, estimated GFR (eGFR) was positively associated with U/P-urea ratio [βscaled=0.08, 95% CI (0.04; 0.13)] but not with the U/P ratio of osmolarity. Considering separately participants with renal function >90 or ≤90mL/min × 1.73 m2, this association was observed only in those with reduced renal function. In the longitudinal study, eGFR declined at a mean rate of 1.2mL/min per year. A significant association was observed between baseline U/P urea ratio and eGFR decline [βscaled=0.08, 95% CI (0.01; 0.15)]. A lower baseline U/P urea ratio was associated with a greater eGFR decline. This study provides evidence that the U/P urea ratio is an early marker of kidney function decline in the general adult population. Urea is easy to measure with well-standardized techniques and at low cost. Thus, the U/P urea ratio could become an easily available tubular marker for evaluating renal function decline.

The association of low birthweight and prematurity on outcomes in children and adults with nephrotic syndrome-a NEPTUNE cohort study.

In single-center studies, both preterm birth and low birth weight (LBW) are associated with worse outcomes in childhood nephrotic syndrome. Using the Nephrotic Syndrome Study Network (NEPTUNE) observational cohort, we tested the hypothesis that in patients with nephrotic syndrome, hypertension, proteinuria status, and disease progression would be more prevalent and more severe in subjects with LBW and prematurity singly or in combination (LBW/prematurity). Three hundred fifty-nine adults and children with focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) and available birth history were included. Estimated glomerular filtration rate (eGFR) decline and remission status were primary outcomes, and secondary outcomes were kidney histopathology, kidney gene expression, and urinary biomarkers. Logistic regression was used to identify associations with LBW/prematurity and these outcomes. We did not find an association between LBW/prematurity and remission of proteinuria. However, LBW/prematurity was associated with greater decline in eGFR. This decline in eGFR was partially explained by the association of LBW/prematurity with APOL1 high-risk alleles, but the association remained after adjustment. There were no differences in kidney histopathology or gene expression in the LBW/prematurity group compared to normal birth weight/term birth. LBW and premature babies who develop nephrotic syndrome have a more rapid decline in kidney function. We did not identify clinical or laboratory features that distinguished the groups. Additional studies in larger groups are needed to fully ascertain the effects of (LBW) and prematurity alone or in combination on kidney function in the setting of nephrotic syndrome.

Optic Nerve Head Capillary Network Quantified by Optical Coherence Tomography Angiography and Decline of Renal Function in Type 2 Diabetes: A Three-Year Prospective Study

To assess the association of optic capillary perfusion with decline in the estimated glomerular filtration rate (eGFR) and to clarify its added value. Prospective, observational cohort study. Patients with type 2 diabetes mellitus without diabetic retinopathy (non-DR) underwent standardized examinations annually during a 3-year follow-up period. The superficial capillary plexus (SCP), deep capillary plexus (DCP), and radial peripapillary plexus (RPC) of optic nerve head (ONH) were visualized using optical coherence tomography angiography (OCTA), and the perfusion density (PD) and vascular density were quantified for the whole image and circumpapillary regions of the ONH. The lowest tercile of annual eGFR slope was defined as the rapidly progressive group, and the highest tercile was considered the stable group. A total of 906 patients were included for 3-mm×3-mm OCTA analysis. After adjusting for other confounders, each 1% decrease in baseline whole en face PD in SCP and RPC was associated with accelerated rates of decline in eGFR by -0.53 mL/min/1.73/m2 per year (95% confidence interval [CI] -0.17 to -0.90; P=.004) and -0.60 mL/min/1.73/m2 per year (95% CI 0.28-0.91), respectively. Adding both whole-image PD in SCP and whole-image PD in RPC to the conventional model increased the area under the curve from 0.696 (95% CI 0.654-0.737) to 0.725 (95% CI 0.685-0.765; P=.031). Another cohort of 400 eligible patients with 6-mm×6 mm OCTA imaging validated the significant associations between ONH perfusion and rate of eGFR decline (P < .05). Reduced capillary perfusion of ONH in patients with type 2 diabetes mellitus is associated with a greater eGFR decline, and it has additional predictive value for detecting an early stage and progression.

Pregnancy History and Kidney Disease Progression Among Women Enrolled in Cure Glomerulonephropathy

Preeclampsia increases the risk for future chronic kidney disease (CKD). Among those diagnosed with CKD, it is unclear whether a prior history of preeclampsia, or other complications in pregnancy, negatively impact kidney disease progression. In this longitudinal analysis, we assessed kidney disease progression among women with glomerular disease with and without a history of a complicated pregnancy. Adult women enrolled in the Cure Glomerulonephropathy study (CureGN) were classified based on a history of a complicated pregnancy (defined by presence of worsening kidney function, proteinuria, or blood pressure; or a diagnosis of preeclampsia, eclampsia, or hemolysis, elevated liver enzymes, and low platelets [HELLP] syndrome), pregnancy without these complications, or no pregnancy history at CureGN enrollment. Linear mixed models were used to assess estimated glomerular filtration rate (eGFR) trajectories and urine protein-to-creatinine ratios (UPCRs) from enrollment. Over a median follow-up period of 36 months, the adjusted decline in eGFR was greater in women with a history of a complicated pregnancy compared to those with uncomplicated or no pregnancies (-1.96 [-2.67,-1.26] vs.-0.80 [-1.19,-0.42] and-0.64 [-1.17,-0.11] ml/min per 1.73 m2 per year, P= 0.007). Proteinuria did not differ significantly over time. Among those with a complicated pregnancy history, eGFR slope did not differ by timing of first complicated pregnancy relative to glomerular disease diagnosis. A history of complicated pregnancy was associated with greater eGFR decline in the years following glomerulonephropathy (GN) diagnosis. A detailed obstetric history may inform counseling regarding disease progression in women with glomerular disease. Continued research is necessary to better understand pathophysiologic mechanisms by which complicated pregnancies contribute to glomerular disease progression.

Clinical outcomes among young patients with Fabry disease who initiated agalsidase beta treatment before 30 years of age: An analysis from the Fabry Registry.

Clinical manifestations of classic Fabry disease (α-galactosidase A deficiency) usually occur in childhood, while complications involving major organs typically develop in adulthood. Outcomes of Fabry-specific treatment among young patients have not been extensively reported. Our aim was to analyze clinical outcomes among patients aged 5-30 years at initiation of treatment with agalsidase beta using data from the Fabry Registry (NCT00196742, sponsor: Sanofi). Reported GLA variants were predicted to be associated with the classic phenotype or not classified in fabry-database.org. Linear mixed models were conducted to assess changes over ≥2-year follow-up in the estimated glomerular filtration rate (eGFR) stratified by low (LRI) and high (HRI) renal involvement (defined by proteinuria/albuminuria levels), and changes in interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) Z-scores stratified by median age at first treatment. Self-reports ('yes'/'no') of abdominal pain, diarrhea, chronic peripheral pain (denoting neuropathic pain), and acute pain crises at baseline were compared with reports after ≥0.5-year and ≥2.5-year follow-up using McNemar's test. Male (n = 117) and female patients (n = 59) with LRI initiated treatment at a median age of 19.9 and 23.6 years, respectively, and were followed for a median of 6.3 and 5.0 years, respectively. The eGFR slopes were -1.18 (Pfrom 0 <0.001) and -0.92 mL/min/1.73 m2/year (Pfrom 0 = 0.040), respectively. Males with HRI (n = 23, median UPCR 1.0 g/g), who started treatment at a median age of 26.7 years, had an eGFR slope of -2.39 mL/min/1.73 m2/year (Pfrom 0 <0.001; Pdifference = 0.055, as compared with the slope of -1.18 mL/min/1.73 m2/year for LRI males) during a median follow-up of 5.6 years. Echocardiographic variables were stable among males, regardless of age, and among young females (median follow-up >5.5 years and ≥4.5 years, respectively). Older females (treatment initiation at median age 27.5 years) had a slope of LVPWT Z-scores of 0.18/year (n = 12, Pfrom 0 = 0.028), whereas IVST Z-scores remained stable (n = 13, 0.10/year, Pfrom 0 = 0.304) during a median follow-up of ≥3.7 years. These slopes did not significantly differ from slopes of younger females. Reports of chronic peripheral pain and acute pain crises by males, and of diarrhea and acute pain crises by females, significantly reduced after a median follow-up of ≥4.0 years. After a median follow-up of ≥5.4 years, reports of all four symptoms significantly decreased among males, whereas among females only reports of abdominal pain significantly decreased. During sustained treatment with agalsidase beta in young Fabry patients with a predicted classic phenotype or with unclassified GLA variants with similar characteristics, the decline in eGFR was modest among male and female patients with LRI. The greater decline in eGFR among older, proteinuric (i.e., HRI) males may suggest a benefit of earlier treatment. Overall, echocardiographic variables remained stable, particularly among males and younger females. Significant reductions in symptom reports occurred primarily among males after longer follow-up and were less noticeable among females. These observed trends are suggestive of an overall improvement after treatment in young patients, but warrant larger longitudinal studies.

Effect of Orthostatic Hypotension on Kidney Function

Background: The association between orthostatic hypotension (OH) and long-term changes in kidney function in the general population is not yet well known. Methods: We performed a population-based cohort study based on data from the Korean Genome and Epidemiology Study (KoGES). The primary exposure was the presence of classic OH, defined as a postural drop in blood pressure (systolic blood pressure ≥20 mm Hg and/or diastolic blood pressure ≥10 mm Hg) at 2 min of standing after 5 min of supine rest. The primary outcome was a 12-year change in kidney function, assessed by subtracting the baseline estimated glomerular filtration rate (eGFR) from the eGFR at 12 years of follow-up. Results: Our study included 5,905 participants (median [interquartile range] age, 49 [44–58] years; 46% males) who met inclusion and exclusion criteria. Classic OH was detected in 268 (4.5%) of the total participants. In the regression analyses, participants with classic OH had a greater decline in eGFR over 12 years compared with those without classic OH; the fully adjusted beta coefficient and 95% confidence intervals (95% CIs) were −1.74 (−3.07, −0.40). Furthermore, classic OH was associated with 27% greater risk of a 30% decline in kidney function compared with those without classic OH; fully adjusted hazard ratio and 95% CIs were 1.27 (1.07, 1.49). Conclusions: Classic OH can negatively affect long-term kidney function in the general population.

Association of the Urine-to-Plasma Urea Ratio With CKD Progression

The urine-to-plasma (U/P) ratio of urea is correlated with urine-concentrating capacity and associated with progression of autosomal dominant polycystic kidney disease. As a proposed biomarker of tubular function, we hypothesized that the U/P urea ratio would also be associated with progression of more common forms of chronic kidney disease (CKD). Observational cohort study. 3,723 adults in the United States with estimated glomerular filtration rate (eGFR) of 20-70 mL/min/1.73 m2, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. U/P urea ratio, calculated from 24-hour urine collections and plasma samples at baseline. Associations of U/P urea ratio with eGFR slope, initiation of kidney replacement therapy (KRT), and CKD progression, defined as 50% decline in eGFR or incident KRT. Multivariable linear mixed-effects models tested associations with eGFR slope. Cox proportional hazards models tested associations with dichotomous CKD outcomes. The median U/P urea ratio was 14.8 (IQR, 9.5-22.2). Compared with participants in the highest U/P urea ratio quintile, those in the lowest quintile had a greater eGFR decline by 1.06 mL/min/1.73 m2 per year (P< 0.001) over 7.0 (IQR, 3.0-11.0) years of follow-up observation. Each 1-SD lower natural log-transformed U/P urea ratio was independently associated with CKD progression (HR, 1.22 [95% CI, 1.12-1.33]) and incident KRT (HR, 1.22 [95% CI, 1.10-1.33]). Associations differed by baseline eGFR (P interaction= 0.009). Among those with an eGFR≥30 mL/min/1.73 m2, each 1-SD lower in ln(U/P urea ratio) was independently associated with CKD progression (HR, 1.30 [95% CI, 1.18-1.45]), but this was not significant among those with eGFR<30 mL/min/1.73 m2 (HR, 1.00 [95% CI, 0.84-1.20]). Possibility of residual confounding. Single baseline 24-hour urine collection for U/P urea ratio. In a large and diverse cohort of patients with common forms of CKD, U/P urea was independently associated with disease progression and incident kidney failure. Associations were not significant among those with advanced CKD at baseline.

Progression of Chronic Kidney Disease Following Radical and Partial Nephrectomy

ObjectiveTo compare renal functional outcomes, as determined by percent decline in estimated glomerular filtration rate (eGFR) and CKD stage progression following radical (RN) and partial nephrectomy (PN) stratified by preoperative CKD stage. Materials and MethodsWe retrospectively evaluated adults treated with RN or PN between 1980 and 2018 for unilateral, sporadic, solid renal masses. Multivariable linear models for percent change in eGFR (n = 3046) and competing-risk Cox proportional hazards models for increase in CKD staging (n = 5805) were used to determine if there was a significant interaction between type of surgery (RN vs PN) and preoperative CKD stage. ResultsPercent change in eGFR at 1 year was significantly worse for RN (n = 1724; 57%) compared with PN (n = 1322; 43%) for all preoperative CKD stages. RN (n = 3227; 56%) was more likely to result in CKD stage progression compared with PN (n = 2578; 44%) for preoperative CKD stages I-IIIb (P <.001) but not for CKD stage IV (P = .8). ConclusionRN was more likely to result in decline in eGFR and CKD stage progression compared to PN for patients with preoperative CKD stage IIIb or less. Additionally, RN was associated with a significantly greater decline in eGFR at 1 year relative to PN in the CKD stage IV subset. Our data support performing PN for renal preservation when feasible.

397-P: eGFR Changes from Adolescence into Young Adulthood in Type 1 Diabetes: Evaluation of Novel eGFR Formulae

Background: Diabetic kidney disease (DKD) is one of the leading causes of CKD and ESRD. Decline in eGFR represents an early marker of DKD that may precede microalbuminuria. The optimal eGFR formula during transition from adolescence into adulthood remains unclear. Objective: To assess longitudinal change in eGFR in youth with T1D transitioning to young adulthood using CKiDU25 creatinine-sex-adjusted (CKiDU25-1) , CKiDU25 combined-creatinine-cystatin (CKiDU25-2) , and CKDEPI40 eGFR formulas. Methods: eGFR was calculated at four time points. Subsequently, linear mixed effect model was used to calculate subject specific eGFR slopes. The percentage of decliners, defined as eGFR slope &amp;lt;/= -3ml/min/1.73m2/year, corresponding to larger eGFR decline was determined. Relationships between eGFR slope and average A1C, ACR, sex, and diabetes duration was assessed using linear regression. Results: There were 99 participants, of which 45% were male, assessed over an average of 7.4 ± 1 years, beginning at 14 ±1.7 to 21.3 ± 2.1 years. Mean eGFR for CKiDU25-1 was 108.1 ± 13.1, slope of -2.9 ± 2.9, and 44% decliners. Mean eGFR for CKiDU25-2 was 104.8 ± 11.9, slope of -2.7 ± 2.2 and 42% decliners. Mean eGFR for CKDEPI40 was 114.8 ± 6.9, slope of 0.8 ± 0.9 and no eGFR decliners. Comparison of all three eGFRs and slopes showed no significant difference between CKiD-1 and CKiD-2, however there was significant differences between CKDEPI40 and both CKiDU25 eGFR and slopes. There was a significant relationship between sex and eGFR slope with males having greater decline in eGFR with all formulae. No significant relationship was found between eGFR slope and ACR, A1C and diabetes duration. Conclusion: CKiDU25-1 and CKiDU25-2 formulae provide similar eGFRs and eGFR slopes while the CKDEPI40 had a higher mean eGFR and no change in eGFR over time. If cystatin-C is not available, CKiDU25-1 provides a suitable alternative for assessment of eGFR changes in youth with type 1 diabetes transitioning into early adulthood. Disclosure F.Babalola: None. E.B.Sochett: None. J.Curtis: None. R.Moineddin: None. Y.T.Elia: None. J.W.Scholey: n/a. D.Cherney: Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research &amp; Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk , Mitsubishi Tanabe Pharma Corporation, Sanofi, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. C.A.White: None. F.H.Mahmud: None.

Cutaneous Ureterostomy or Ileal Conduit Urinary Diversion: Can We Spare the Bowel Following Radical Cystectomy in Patients with Solitary Functioning Kidney?

To compare the outcomes between cutaneous ureterostomy and ileal conduit urinary diversion in patients with solitary functioning kidney, undergoing radical cystectomy. This study was a retrospective analysis of the patients, with solitary functioning kidney, who underwent radical cystectomy with either cutaneous ureterostomy or ileal conduit from January 2014 to May 2019. Baseline characteristics, perioperative outcomes, and follow-up renal function were evaluated and compared. For renal function outcomes, we assessed the estimated glomerular filtration rate (eGFR) and included patients with a follow-up of at least 2years. A total of 43 patients were included in the study, 23 of them underwent cutaneous ureterostomy and 20 underwent ileal conduit urinary diversion. The two groups were similar with respect to their baseline demographic and clinical characteristics. Operative time (p < 0.001), time to drain removal (p = 0.016), postoperative length of hospital stay (p = 0.018), and bowel-related complications (p = 0.047) were significantly lower in patients who underwent cutaneous ureterostomy. The eGFR was comparable at baseline, and till 1year of follow-up. But, there was a greater decline in eGFR over 2years, in patients who received cutaneous ureterostomy (p = 0.039). The present study shows that cutaneous ureterostomy has better perioperative, and comparable short-term renal function outcomes over ileal conduit urinary diversion. However, over 2years of follow-up, there was an increased likelihood, and greater degree of decline in eGFR in patients who received cutaneous ureterostomy.

MP42-12 HIGHER PREOPERATIVE EGFR IS A PREDICTOR OF WORSE RENAL FUNCTION DECLINE AFTER ROBOTIC ASSISTED RADICAL CYSTECTOMY

You have accessJournal of UrologyCME1 May 2022MP42-12 HIGHER PREOPERATIVE EGFR IS A PREDICTOR OF WORSE RENAL FUNCTION DECLINE AFTER ROBOTIC ASSISTED RADICAL CYSTECTOMY Shirin Razdan, Benjamin Eilender, John Pfail, Mariely Garcia, Daniel Ranti, Shoshana Rosenzweig, Abolfazl Hosseini, Jari Radros, Reza Mehrazin, Peter Wiklund, and John Sfakianos Shirin RazdanShirin Razdan More articles by this author , Benjamin EilenderBenjamin Eilender More articles by this author , John PfailJohn Pfail More articles by this author , Mariely GarciaMariely Garcia More articles by this author , Daniel RantiDaniel Ranti More articles by this author , Shoshana RosenzweigShoshana Rosenzweig More articles by this author , Abolfazl HosseiniAbolfazl Hosseini More articles by this author , Jari RadrosJari Radros More articles by this author , Reza MehrazinReza Mehrazin More articles by this author , Peter WiklundPeter Wiklund More articles by this author , and John SfakianosJohn Sfakianos More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002608.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In patients with muscle invasive bladder cancer or high risk noninvasive bladder cancer, renal function decline is a concern after radical cystectomy with urinary diversion. The pathophysiology of this decline is multifactorial, with subclinical acidosis and metabolic derangements from the diversion thought to contribute. It is unknown whether patients with baseline chronic kidney disease (CKD) are at increased risk of further decline in renal function. METHODS: We performed a retrospective review of two high volume robotic assisted radical cystectomy (RARC) centers between 2016-2020. Preoperative demographics and comorbidities were collected. Postoperative estimated glomerular filtration rate (eGFR) was calculated at 12 and 24 months to determine short-term rate in decline of eGFR. Absolute and percent changes in eGFR were calculated. RESULTS: There were a total of 555 patients who underwent RARC. Men comprised 76.2% of the cohort. Neoadjuvant chemotherapy was given in 31% of patients and adjuvant chemotherapy was given in 4.81% of patients. Higher preoperative eGFR (B -0.549, 95% CI -0.708 - -0.391, p<0.001) and presence of diabetes mellitus (B -15.414, 95% CI -24.820- -6.008, p=0.001) were significant predictors of eGFR decline at 12 months. At 24 months, presence of diabetes mellitus (B -11.799, 95% CI -21.816 - -1.782, p=0.021) and higher preoperative eGFR (B -0.621, 95% CI -0.796 - -0.446, p<0.001) were correlated with a steeper decline in eGFR. Higher preoperative eGFR was also predictive of upstaging to CKD3 or higher post operatively (OR 1.019, 95% CI 1.004-1.034, p=0.015). Intracorporeal diversion was protective, whereas presence of hypertension, diabetes mellitus, and higher preoperative eGFR predicted greater decline in eGFR. CONCLUSIONS: Patients with higher preoperative eGFR and diabetes are at increased risk of renal function decline post RARC at 12 and 24 months. This suggests that patients with risk factors for renal function decline, but otherwise normal renal function at baseline, are a particularly vulnerable population for progression to CKD after RARC and should be counseled and closely followed postoperatively for renal function deterioration. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e735 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shirin Razdan More articles by this author Benjamin Eilender More articles by this author John Pfail More articles by this author Mariely Garcia More articles by this author Daniel Ranti More articles by this author Shoshana Rosenzweig More articles by this author Abolfazl Hosseini More articles by this author Jari Radros More articles by this author Reza Mehrazin More articles by this author Peter Wiklund More articles by this author John Sfakianos More articles by this author Expand All Advertisement PDF DownloadLoading ...

Association of Pre‐Living Kidney Donation Body Mass Index with Post‐Donation Estimated Glomerular Filtration Rate Decline

IntroductionObesity is one of the risk factors for chronic kidney disease (CKD). Whether body mass index (BMI) at pre‐living kidney donation is associated with worsening kidney function of the remaining kidney after donation is unclear. We aim to examine the association between pre‐donation BMI and change in post‐donation estimated glomerular filtration rate (eGFR) in living kidney donors.MethodsA single‐center retrospective cohort study included 14 living kidney donors. Associations between pre‐donation BMI and percentage of eGFR decline at 2 and 7 days post‐donation were examined by multiple linear regression.ResultsOf all 14 living kidney donors, mean age±SD was 52.64±13.46 years old and 50% was female. Mean BMI was 26.90±2.66 kg/m2. The majority were overweight (72%) followed by normal weight (21%) and obese (7%). eGFR at 2‐ and 7‐day post‐donation were significantly lower than pre‐donation eGFR (55.59±12.48 vs. 55.29±11.33 vs. 93.39±14.62, p &lt;0.001; Figure 1). Every 1 kg/m2 increase in pre‐donation BMI was associated with 0.1% greater decline in eGFR at 2‐day post‐donation, while eGFR decline was up to 1.4% at 7‐day post‐donation (β2day±SE 0.149±0.716, p 0.861, 95%CI ‐1.668, 1.966; Figure 2A and β7day ±SE 1.368±0.834, p 0.080, 95%CI ‐0.191, 2.928; Figure 2B). After adjusted for age, gender, ethnicity, pre‐donation eGFR, and interaction term between age and pre‐donation eGFR, the magnitude of eGFR decline post‐donation were greater for both 2‐ and 7‐day post‐donation; however, only the 7‐day post‐donation eGFR decline was statistically significant without the interaction between age and pre‐donation eGFR (β2day±SE 0.653±0.977, p 0.525, 95%CI ‐1.657, 2.963, pinteraction 0.045 and β7day±SE 2.068±0.800, p 0.036, 95%CI 0.176, 3.959, pinteraction 0.541).ConclusionsHigher pre‐donation BMI is associated with greater eGFR decline at 7‐day, but not 2‐day, post‐donation. Pathological glomerular hyperfiltration from overweight or obesity may counteract with physiological glomerular hyperfiltration from acquired solitary kidney post‐donation leading to worsening post‐donation eGFR decline.

Association of urinary angiotensinogen with renal arteriolar remodeling in chronic kidney disease.

Renin-angiotensin system (RAS) might be associated with arteriolar remodeling. The present study aimed to explore the hitherto unknown relationship between renal RAS and renal arteriolar remodeling and to elucidate whether altered renal RAS subsequently affects renal function in patients with chronic kidney disease (CKD). In this retrospective study, patients with various CKDs not using RAS inhibitors who underwent renal biopsy were included in cross-sectional and longitudinal analyses. Urinary angiotensinogen (UAGT) levels and wall/lumen ratio (WLR) were determined to evaluate renal RAS and renal arteriolar remodeling, respectively. The association between ln(UAGT) and ln(WLR) was cross-sectionally examined using a liner regression model. Furthermore, the association of ln(UAGT) with subsequent changes in estimated glomerular filtration rate (eGFR) per year were longitudinally examined in the largest subgroup of patients who were diagnosed with IgA nephropathy. In the overall cohort (n = 54), the median age, blood pressures, eGFR, and WLR were 37 years, 120/73 mmHg, 85 ml/min per 1.73 m2, and 0.93, respectively. Ln(UAGT) was significantly and positively associated with ln(WLR) even after adjusting for classical and nonclassical clinical renal risk factors. In patients with IgA nephropathy, higher ln(UAGT) was associated with higher ln(WLR). Ln(UAGT) also tended to be associated with a greater decline in eGFR per year over a median period of 8.7 years, even after adjusting for potential confounding factors. In patients with CKD, renal RAS might be associated with renal arteriolar remodeling and future decline in eGFR, independent of potential risk factors.