Albuminuria In Adults Research Articles

Impact of Weekend Catch-Up Sleep on CKD and Albuminuria in Adults: Evidence from NHANES, 2017-2020

Impact of Weekend Catch-Up Sleep on CKD and Albuminuria in Adults: Evidence from NHANES, 2017-2020

#457 Sparsentan has direct effects on the glomerular capillary wall to attenuate increased permeability after exposure to nephrotic syndrome plasma

Abstract Background and Aims The glomerular endothelial glycocalyx (eGlx), a luminal layer of proteoglycans, glycoproteins and glycolipids, forms the first part of the glomerular filtration barrier (GFB). Nephrotic syndrome (NS) describes a group of pathologies of the renal glomerulus that result in proteinuria and is associated with glomerular endothelial dysfunction. Current treatments are broad and non-specific. Sparsentan is a single-molecule dual endothelin type-A and angiotensin II type 1 receptor antagonist that has received accelerated approval in the United States for the reduction of proteinuria in adults with IgA nephropathy at high risk of disease progression. Our validated glomerular permeability assay directly measures the albumin permeability (Ps’alb)of capillary loops within individually trapped glomeruli [1]. This ex vivo assay is independent of haemodynamic factors and tubular albumin handling – factors known to affect urine protein concentrations. This work examines whether sparsentan could reduce glomerular albumin permeability in NS, by preserving the eGlx to maintain the GFB. Method Human NS plasma samples were collected under ethical consent from 3 patients that had undergone plasma exchange from periods when they were in relapse (RL), or subsequent remission (RM). Adult male Sprague Dawley rats (175–200 g) were perfused with 4% Ringer BSA solution. Glomeruli were isolated on ice by graded sieving from the cortex of each kidney. Glomeruli were incubated, in the presence of AF488-conjugated BSA (AF488-BSA, 30 μg/ml) and R18 (36.5 μg/ml), with 10% plasma from NS patients for 1 hour, and simultaneously treated with sparsentan (0.1 μM, 1 μM and 10 μM) or vehicle. The glomerular Ps’alb assay was used to measure changes in albumin permeability. We applied a fluorescence profile peak-to-peak confocal imaging technique to treated glomeruli to assess glomerular eGlx thickness [2]. Results Human NS patients in RL had a significantly greater proteinuria compared to RM (RL, 10, 000 ± 1, 354 mg/g; RM, 95.3 ± 59.7 mg/g, P = 0.017). Incubation of rat glomeruli with RL plasma induced a significant increase in Ps’alb (RM+vehicle, 6.0 × 10−7 ± 0.12 × 10−7 cm/s; RL+vehicle, 10.9 × 10−7 ± 0.84 × 10−7 cm/s, P < .001) with a significant reduction in glomerular eGlx thickness (RM+vehicle, 210 ± 21.2 nm; RL+vehicle, 109 ± 7.9 nm, P = .027), compared to rat glomeruli incubated with paired RM plasma. Sparsentan-treated RL incubated glomeruli were protected from both the increase in Ps’alb (RL+spars 10 µM, 6.3 × 10−7 ± 0.19 × 10−7 cm/s, P < .001) and the loss in glomerular eGlx (RL+spars 10 µM, 222 ± 8.5 nm, P = .013), to a level comparable to RM incubated glomeruli. The effect of sparsentan on Ps’alb was dose dependent (RL+spars 1 µM, 8.0 × 10−7 ± 0.46 × 10−7 cm/s; RL+spars 0.1 µM, 9.6 × 10−7 ± 0.22 × 10−7 cm/s) with Ps’alb changes correlating inversely with glomerular eGlx thickness (r² = 0.75, P < .0001). In RM glomeruli, sparsentan alone had no effect on Ps’alb compared with vehicle (RM+spars 10 µM, 6.2 × 10−7 ± 0.25 × 10−7 cm/s, P = .590), suggesting no effect on otherwise healthy capillaries. Conclusion We have shown that dual inhibition of endothelin and angiotensin receptors, with sparsentan, preserves the glomerular eGlx resulting in normalised glomerular permeability in NS. These findings suggest that the direct action of sparsentan on the GFB could help maintain barrier integrity in NS, in particular by glycocalyx protection.

#2459 Matching-adjusted indirect comparison of eGFR in patients with immunoglobulin A nephropathy treated with Nefecon (TRF budesonide) or sparsentan

Abstract Background and Aims Primary immunoglobulin A nephropathy (IgAN) is an immune-mediated disease that can lead to kidney failure, need for dialysis and kidney transplantation, and early death. IgAN is the most common type of primary glomerulonephritis globally, with an estimated worldwide incidence of 2.5 per 100 000 individuals per year. Estimated glomerular filtration rate (eGFR) is a measure of renal function and is accepted as a surrogate endpoint for clinical trials evaluating kidney function deterioration. In December 2023, the US Food and Drug Administration (FDA) granted full approval to Nefecon (marketed as Tarpeyo® by Calliditas Therapeutics), a targeted-release formulation of budesonide, to reduce the loss of kidney function in adults with IgAN at risk of disease progression, based on the Phase 3 NefIgArd clinical trial. In February 2023, sparsentan (marketed as Filspari™ by Travere Therapeutics) was granted accelerated approval by the FDA to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression, generally a urine protein–creatinine ratio (UPCR) ≥1.5 g/g, based on the Phase 3 PROTECT study. Matching-adjusted indirect comparison (MAIC) is a widely accepted and relevant methodology for comparing treatments across trials in the absence of head-to-head comparisons. In this analysis, we aimed to compare the effects of Nefecon and sparsentan on kidney function deterioration in patients with IgAN, as assessed by eGFR. Method An anchored MAIC was performed to estimate the relative effect of Nefecon and sparsentan on the absolute eGFR change from baseline at 9, 12 and 24 months, with common comparators of optimized renin–angiotensin system inhibition for NefIgArd and irbesartan for PROTECT. Patient-level data from NefIgArd were used to select a population matched to PROTECT, and the following baseline characteristics were used to determine the weights: mean age (years), sex (% male), race (% white), mean eGFR (mL/min/1.73 m2), mean UPCR (g/g), urine albumin–creatinine ratio (UACR) (% with UACR >1.1 g/g), and urinary protein excretion (% with urinary protein excretion >1.8 g/day). Absolute change in eGFR was analyzed using a mixed model for repeated measures (MMRM) method, including baseline, 3-, 6-, 9-, 12-, 18- and 24-month data, baseline eGFR, baseline eGFR-by-time interaction, treatment, and treatment-by-time interaction. The MAIC weights were incorporated into the MMRM. A Bayesian fixed-effects network meta-analysis was performed on the relative effect from PROTECT and the weighted relative effect from NefIgArd, measured by the estimated absolute change from baseline in eGFR. Results The matching-adjustment of the NefIgArd patient population to the PROTECT population is shown in Table 1. The weighted NefIgArd population exhibits very similar baseline characteristics to the PROTECT population. The effective sample size of the weighted NefIgArd population is 208. Results from the anchored MAIC showed statistically and clinically significant favorable effects of Nefecon versus sparsentan on eGFR for all time points analyzed (Fig. 1). Mean differences in the absolute change in eGFR of 5.68 mL/min/1.73 m2 (95% credible interval [Crl] 3.14, 8.20; p < 0.001), 3.48 mL/min/1.73 m2 (95% Crl 0.97, 5.97; p = 0.006) and 3.28 mL/min/1.73 m2 (95% Crl 0.02, 6.51; p = 0.048) were observed when comparing Nefecon with sparsentan at 9 months vs 36 weeks, 12 months vs 48 weeks, and 24 months vs 106 weeks, respectively. Conclusion After accounting for differences in the patient populations from the NefIgArd and PROTECT trials, the anchored MAIC showed that treatment with Nefecon 16 mg/day for 9 months was associated with greater eGFR benefit compared with continuous treatment with sparsentan 400 mg/day over 2 years, with significant differences observed as early as 9 months after treatment initiation and sustained up to 2-years of follow-up.

Enteric-Coated Capsules Providing Reliable Site-Specific Drug Delivery to the Distal Ileum.

Nefecon, a targeted-release capsule formulation of budesonide approved for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy, targets overproduction of galactose-deficient immunoglobulin A type 1 in the Peyer's patches at the gut mucosal level. To investigate whether the commercial formulation of Nefecon capsules reliably releases budesonide to the distal ileum, a human study was conducted with test capsules reproducing the delayed-release function of Nefecon capsules. Caffeine was included in the test capsules as a marker for capsule opening in the gut since it appears rapidly in saliva after release from orally administered dosage forms. Magnetic resonance imaging with black iron oxide was used to determine the capsule's position in the gut at the time caffeine was first measured in saliva and additionally to directly visualize dispersion of the capsule contents in the gut. In vitro dissolution results confirmed that the test capsules had the same delayed-release characteristics as Nefecon capsules. In 10 of 12 human volunteers, the capsule was demonstrated to open in the distal ileum; in the other two subjects, it opened just past the ileocecal junction. These results compared favorably with the high degree of variability seen in other published imaging studies of delayed-release formulations targeting the gut. The test capsules were shown to reliably deliver their contents to the distal ileum, the region with the highest concentration of Peyer's patches.

Non-linear relationship between body roundness index and albuminuria among children and adolescents aged 8-19 years: A cross-sectional study.

Obesity has been found to be correlated with numerous health issues, including an elevated risk of albuminuria in adults. However, this correlation is still controversial among children and adolescents, as several recent large-scale cross-sectional studies have observed a negative correlation between obesity and albuminuria. Our study aimed to investigate the link between the body roundness index (BRI) and albuminuria among children and adolescents, in order to further understand the correlation between obesity and albuminuria in this demographic. We employed information from the National Health and Nutrition Examination Survey (NHANES) 1999-2010 for cross-sectional analysis. Weighted logistic regression was employed to explore the linear relationship between BRI and albuminuria, with subgroup analyses performed for more detailed insights. Weighted linear regression analysis was employed to explore the relationship between BRI and the urine albumin-creatinine ratio (UACR). Additionally, we applied smooth curve fitting to investigate their non-linear relationship and conducted threshold effect analysis to identify any turning point. In this study of 15,487 participants aged 8-19 years, multivariate logistic regression analysis revealed a significant negative correlation between BRI and albuminuria (OR = 0.616, 95%CI: 0.526-0.722). The relationship between BRI and UACR, as shown by multivariate linear regression analysis, was significantly inversely correlated (β: -5.424, 95%CI: -7.416 to -3.433). Furthermore, smooth curve fitting and threshold effect analysis showed a non-linear relationship between BRI and albuminuria, with a BRI inflection point identified at 2.906. These findings of our study suggest a significant nonlinear negative association between BRI and the presence of albuminuria among children and teenagers, and maintaining an appropriate BRI may decrease the occurrence of albuminuria in this population.

Sparsentan is superior to losartan in the gddY mouse model of IgA nephropathy.

The mechanism leading to the development of immunoglobulin A nephropathy (IgAN) remains to be completely understood. Endothelin-1 (ET-1) as well as angiotensin II (AngII) promote glomerular injury, tubulointerstitial inflammation and fibrosis leading to chronic kidney disease. Sparsentan, a dual endothelin angiotensin receptor antagonist, recently received accelerated approval in the USA for the reduction of proteinuria in adults with IgAN at high risk of disease progression. To elucidate the mechanisms by which sparsentan is efficacious in IgAN, we examined the effect of treatment in gddY mice, a spontaneous IgAN mouse model, versus the monoselective angiotensin II type 1 receptor (AT1R) antagonist, losartan, on the development of renal injury at doses resulting in similar blood pressure lowering. Four-week-old gddY mice were given control chow, chow containing sparsentan or drinking water containing losartan until 12 or 20 weeks old. Remarkably, the albumin:creatine ratio (ACR) was attenuated more rapidly and to a greater extent in mice treated with sparsentan than those treated with losartan. The decrease in ACR from baseline after 4 weeks of treatment correlated with beneficial effects of sparsentan on glomerulosclerosis and protection of podocytes and glycocalyx after 16 weeks of treatment across treatment groups; thus, sparsentan treatment delayed development of renal injury to a greater extent than losartan. Expression of mRNA for ET-1, endothelin type A receptor and AT1R and proinflammatory genes was upregulated in 12-week-old gddY mice and was prevented by sparsentan and losartan to a comparable extent. The results of this study, and in light of the results of the phase 3 PROTECT trial, provide a novel perspective and understanding of the mechanisms by which sparsentan has a beneficial renoprotective effect against IgAN compared with AT1R antagonism alone.

Practical Considerations for the Use of Sparsentan in the Treatment of Patients with IgAN in Clinical Practice.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. It is characterized by the mesangial deposition of IgA-containing immune complexes, triggering damage to the glomerular filtration barrier that is amplified by the tandem action of endothelin-1 and angiotensin II at their receptors. Proteinuria and progressive glomerular damage cause loss of kidney function in up to 50% of patients within 10-20 years. The risk of progression is strongly associated with persistent proteinuria (>0.75-1 g/day). Current standard of care involves interventions to decrease proteinuria and control blood pressure. Immunosuppressive agents, used in selected patients at high risk for progression, can be associated with significant side effects. Sparsentan, a novel non-immunosuppressive single-molecule Dual Endothelin Angiotensin Receptor Antagonist (DEARA), received FDA accelerated approval based on interim results from the PROTECT trial, which demonstrated that sparsentan-treated patients achieved a significantly greater reduction in proteinuria from baseline versus the active control irbesartan and that sparsentan was generally safe and well tolerated. Sparsentan is the first non-immunosuppressive treatment to be FDA-approved for the reduction of proteinuria in adults with IgAN at high risk of disease progression. We provide practical guidance for the clinical use of sparsentan in adults with IgAN.

Effect of weight loss on proteinuria in adults with type 2 diabetes: A real-world study

AimsTo assess the impact of weight loss on proteinuria in patients with type 2 diabetes (T2DM) in real-world settings. MethodsA total of 1054 participants were categorized based on weight change from baseline to one-year follow-up: weight gain (≥3%), stable weight, or weight loss (≥3%). Proteinuria outcomes were defined as urinary albumin/creatinine ratio (UACR) progression (≥30 % increase), UACR regression (≥30 % reduction), or UACR stable. Ordered logistic regression analysis evaluated the relationship between weight loss and UACR regression. ResultsOf the 1054 participants, 44.5 % were overweight, and 24.1 % were obese. Patients with obesity were at higher risk of developing proteinuria (OR, 1.783; 95 %CI, 1.195 to 2.659). Weight loss was associated with an 83.3 % increase in UACR regression compared to weight gain (OR, 1.833; 95 % CI, 1.262 to 2.663; P = 0.001). This association remained consistent across most subgroups and stronger in males (P for interaction = 0.023), with a 6 % UACR regression for every 1 kg weight loss (OR, 1.06; 95 % CI, 1.02 to 1.10; P = 0.003). ConclusionsOur real-world study reveals that weight reduction is associated with UACR regression in patients with T2DM, regardless of the approach used for weight management, and the association was much stronger in males.

Double-Blind Randomized Study to Evaluate the Effect of Hydroxycarbamide on Albuminuria in Adults with Sickle Cell Disease: Sikamic (SIklos on Kidney Function and AlbuMInuria Clinical Trial)

Background Sickle cell disease (SCD) is associated with a high frequency of chronic kidney disease, which is an independent risk factor for mortality in this population. SCD-associated nephropathy (SCAN) is an emerging concern, characterized by significant albuminuria and progressive deterioration of renal function with a prevalence of up to 26% to 68% in SCD adult patients (Falk 1992, Powars 2005, Yeruva 2016, Ataga 202). Because of rapid decline of estimated glomerular filtration rate (eGFR) is a frequent finding in this population (Derebail 2019, Ataga KI 2021), early diagnosis of SCAN and identification of associated clinical and biologic risk factors are crucial for initiating kidney-protective therapy at early stages of renal impairment. Albuminuria serves as a relevant biomarker for detecting early glomerular damage in SCD patients (Audard 2017). To date, Hydroxycarbamide (HU) remains the cornerstone treatment for managing SCD patients, and its efficacy is primarily attributed to its ability to increase fetal hemoglobin (HbF) levels (Segal 2008). Several observational studies conducted in adult SCD patients have shown that HU may have renal protective effects, making it a promising therapeutic option, but until now, randomized clinical trials confirming this hypothesis are missing (Bartolucci 2015, Laurin 2014). Method SIKAMIC (SIklos on Kidney Function and AlbuMInuria Clinical Trial) is an international (France and Africa), phase IIb, double-blind, randomized, placebo-controlled study. The main objective is to assess the effect of HU on albuminuria levels in SCD adult patients after 6 months of treatment. Eligible patients are of the SS or Sβ0 genotype with a mean albuminuria value (assessed by albumin-to-creatinine ratio: ACR) above 3 and less than 100 mg/mmol, on three urine samples taken one day apart. Patients should not have received HU treatment within the previous 6 months and should not be taking conventional kidney-protecting measures (ACE inhibitors or ARA2) and having blood transfusion in the last 3 months. Patient with an eGFR rate < 60 and ≥ 140 ml/min/1,73m² are excluded from the study. Patients receive either HU at a dosage of 15mg/kg/day or placebo for 6 months, and responders (patient achieving at least a 30% decrease of the ACR baseline at 6 months) have the option to continue the study for an additional six months. Recruitment started in August 2019 in France and in October 2021 in Africa and was extended until June 2023 due to challenge in finding HU-Naïve patients. The end of the study is planned in June 2024 with safety monitoring conducted by an Independent Data Monitoring Committee throughout. Results During the recruitment period, 179 patients were screened, 99 were randomized, 34 in France, 65 in Africa (Senegal: 31, Mali: 23, Ivory Coast: 11) ( Figure 1). The main reason for screen failure was mean ACR < 3mg/mmol. Two patients were excluded from the analysis due to non-compliance with exclusion criteria. Among the 97 patients analyzed, 32 completed the study by June 30, 2023, while 46 were still ongoing treatment, and 19 withdrew before the end of the 6 months follow-up period. The study includes a higher proportion of women (68%), which can be attributed to challenges faced in conducting semen analysis in African countries and the hesitancy to initiate HU treatment without prior semen analysis. The mean age at enrolment was 29.7 ± 9.2 years. Recruitment significantly improved after opening African sites. The study encountered several difficulties, primarily stemming from the challenge of finding HU-naïve patients in France and the high rate of screen failure attributed to non-expected ACR measurement variability and eGFR outside the accepted limits. No safety issues were reported, with 15 well-known adverse events related to HU occurring in 11 patients. Results of the study are expected by the end of 2024. Conclusion This study is the first randomized placebo-controlled study investigating the effect of HU on albuminuria in SCD patients. By employing a complex and robust study design, with ACR measurements at multiple time points, the study will provide valuable insights into the impact of HU on albuminuria levels. Moreover, the collaboration with African countries has highlighted the significance of considering country-specific factors and fostering partnerships to address the unique challenges faced by patients in these regions.

Histopathology Findings and Outcomes of Non-Nephrotic Range Proteinuria in Adults and Children

Histopathology Findings and Outcomes of Non-Nephrotic Range Proteinuria in Adults and Children

Passive Heat Therapy Compared To Aerobic Exercise In Reducing Albuminuria In Adults With Untreated Hypertension

Passive Heat Therapy Compared To Aerobic Exercise In Reducing Albuminuria In Adults With Untreated Hypertension

Budesonide delayed-release capsules to reduce proteinuria in adults with primary immunoglobulin A nephropathy

ABSTRACT Introduction Immunoglobulin A nephropathy (IgAN) is characterized by mesangial deposition of immune complexes containing galactose-deficient IgA1 (Gd-IgA1). This Gd-IgA1 is believed to originate from mucosally sited B cells, which are abundant in the Peyer’s patches-rich distal ileum. Nefecon is a targeted-release form of budesonide developed to act in the distal ileum, thereby exerting a direct action on the mucosal tissue implicated in the pathogenesis of the disease. Areas covered This review discusses IgAN pathophysiology and provides an overview of the current therapeutic landscape, focusing on Nefecon, the first drug to receive accelerated US approval and conditional EU approval for the treatment of patients with IgAN at risk of rapid disease progression. Expert opinion Nefecon trial data thus far have demonstrated a promising efficacy profile, with a predictable pattern of adverse events. Treatment with Nefecon for 9 months reduces proteinuria substantially (Part A of the Phase 3 trial and the Phase 2b trial). A nearly complete prevention of deterioration of renal function has been observed at 12 months in patients at greatest risk of rapid disease progression. Long-term data from Part B of the Phase 3 study will provide 24-month data, furthering understanding of the durability of the 9-month treatment course.

Association of Hand Grip Strength and Albuminuria in Adults Aged over 40 Years: The 2019 Korea National Health and Nutrition Examination Survey (KNHANES VIII-1)

Association of Hand Grip Strength and Albuminuria in Adults Aged over 40 Years: The 2019 Korea National Health and Nutrition Examination Survey (KNHANES VIII-1)

Urinary angiotensinogen is associated with albuminuria in adults with sickle cell anaemia.

We explored the association of novel urinary biomarkers with albumin-creatinine ratio (ACR) in adults with sickle cell anaemia. Of 37 participants, 13 (35.2%) had persistent albuminuria (PA). Urinary levels of clusterin (p = 0.002), retinol-binding protein 4 (p = 0.008), alpha-1 microglobulin (p = 0.002) and angiotensinogen (p = 0.006) were significantly higher in participants with PA than in those without PA. Although univariate analysis showed significant associations between both alpha-1 microglobulin (p = 0.035) and angiotensinogen (p = 0.0021) with ACR, only angiotensinogen was associated with ACR in multivariable analysis (p = 0.04). Our results suggest that urinary angiotensinogen may identify sickle cell anaemia patients at risk for kidney disease.

Sparsentan: First Approval

Sparsentan (FILSPARI™) is an oral, dual endothelin angiotensin receptor antagonist that is being developed by Travere Therapeutics for the treatment of immunoglobulin A (IgA) nephropathy and focal segmental glomerulosclerosis (FSGS). In February 2023, sparsentan received accelerated approval in the USA for reducing proteinuria in adults with primary IgA nephropathy who are at risk of rapid disease progression. This article summarizes the milestones in the development of sparsentan leading to this first approval for IgA nephropathy.

A Case of ALECT2 Renal Amyloidosis Associated with IgG4 Related Kidney Disease, Membranous Nephropathy and Early Diabetic Kidney Injury

Abstract Introduction/Objective ALECT-2 amyloidosis is a rare type of amyloidosis that mostly involves kidneys with other organs rarely affected. It has a high prevalence among patients of Hispanic descent. Membranous nephropathy is one of the most common causes of proteinuria in adults. IgG4-related disease is a systemic disease, which commonly involves the pancreas, but occasionally affects the kidney and manifests as chronic renal insufficiency. Here we describe a very unusual case of concurrence of membranous nephropathy, IgG4 disease involving the kidney, ALECT2 amyloidosis, and early diabetic kidney injury. Methods/Case Report A 49-year-old Hispanic male patient with a history of diabetes and IgG4-related autoimmune pancreatitis and primary sclerosing cholangitis presented with abrupt onset of proteinuria and hypoalbuminemia. A kidney biopsy was performed and showed severe interstitial plasma cell-rich inflammatory infiltrates and interstitial fibrosis which had a storiform pattern. The glomerular basement membranes (GBM) showed focal pinpoint holes but no spikes by silver stain. Immunofluorescence microscopy (IF) showed diffuse and finely granular capillary loop staining for IgG, with Kappa and lambda light chains of equal intensity. IF for Anti-phospholipase A2 receptor (PLA2R) was negative. Immunohistochemical (IHC) stain showed IgG4 positivity in about 60% of IgG-positive plasma cells. Congo red was positive for birefringent deposits predominantly in the interstitium and arteriolar walls with focal deposits in the glomerular mesangium and capillary wall. IHC stain for Amyloid AA and DNAJB9 were negative. Electron microscopy showed scattered subepithelial immune complex-type electron dense deposits consistent with membranous nephropathy, randomly oriented fibrils in interstitium, mesangium and GBM, consistent with amyloidosis, and thickening of GBM (average 559 nm), consistent with early diabetic kidney change. The tissue was sent for mass spectrometry which showed a peptide profile consistent with ALECT-2 (Leukocyte chemotactic factor 2) type amyloidosis. Results (if a Case Study enter NA) NA Conclusion In up to a third of cases reported in the literature, a concomitant renal pathology was present. Diabetic nephropathy was the most common concurrent pathology, to be followed by IgA nephropathy and membranous nephropathy. However, the concurrence of membranous nephropathy, IgG4 disease involving the kidney, ALECT2 amyloidosis, and early diabetic kidney injury has never been described before.

OR28-3 Ethnic Differences in Albuminuria among Adults with Diabetes and Normal Range Estimated Glomerular Filtration Rate (eGFR).

Abstract Background Diabetic kidney disease (DKD) develops in approximately 40% of adults with diabetes and is the leading cause of chronic kidney disease (CKD). Less is known about early DKD, particularly in ethnically diverse populations that include Black, Hispanic/Latinx, and Asian Americans. Current guidelines recommend that patients with diabetes be screened annually for DKD. Albuminuria is the first sign of CKD and is associated with CKD progression, cardiovascular events, and death. This study characterizes ethnic differences in the prevalence of albuminuria in a diverse population of adults with diabetes with normal range eGFR. Methods This retrospective study was conducted in a large healthcare system where patients with diabetes are annually monitored for DKD. We identified adults with diabetes aged 45-74 years, eGFR ≥60 mL/min/m2 based on serum creatinine (using the CKD-EPI equation without race), and assessment of urine albumin-creatinine ratio (ACR), urine protein-creatinine ratio (PCR) and/or urine protein dipstick in 2015. Albuminuria was based on urine ACR (95%), otherwise, from urine PCR (1%) converted to ACR, and, if unavailable, from urine protein dipstick (4%) converted to ACR. The cohort was restricted to patients with diabetes onset after health plan enrollment to calculate diabetes duration. Hypertension was identified by clinical diagnosis. Modified Poisson regression with robust variance was used to examine the association of ethnicity and albuminuria, reporting relative risk (RR) with 95% confidence intervals (CI). Results Among 79,184 adults with diabetes, eGFR ≥60, and urine albumin/protein assessment (age 60.5 ±7.7y, 54.0% male), 40.3% were non-Hispanic White, 9.6% Black, 26.3% Asian/Pacific Islander (PI), and 21.0% Hispanic/Latinx race/ethnicity. 69.9% had hypertension. Overall, 81.7%, 13.8%, and 4.6% had urine ACR <30 (normal), 30 to <300 (microalbuminuria), and ≥300 mg/g (macroalbuminuria), respectively, with albuminuria higher in males than females. By race/ethnicity, the prevalence of [micro/macroalbuminuria] was [15.7/5.4%] Asian/PI, [13.8/4.8%] Black, [13.1/4.5%] Hispanic/Latinx, and [12.8/4.1%] non-Hispanic Whites. Among Asian/PIs, prevalence ranged from [19.5/8.4%] Hawaiian/PI and [18.2/7.1%] Filipino to [14.5/3.6%] Chinese and [11.2/3.4%] South Asian. In multivariable analyses, adjusting for age, sex, diabetes duration, and hypertension, Asian/PI (RR 1.3, CI 1.2-1.3) was associated with higher risk of albuminuria compared to non-Hispanic White, but Black (RR 1.0) and Hispanic/Latinx (RR 1.0) were not. Among Asian/PIs, with Chinese as reference, Filipino (RR 1.3, CI 1.2-1.4) and Hawaiian/PI (RR 1.4, CI 1.3-1.6) had higher risk, South Asian had lower risk (RR 0.7, CI 0.7-0.8), and Japanese and Southeast Asian had similar risk of albuminuria. Conclusions The risk of albuminuria in adults with diabetes and normal range eGFR was higher in Asian/PI adults. Among Asian/PIs, the risk was higher among Filipino and Hawaiian/PI and lower in South Asian compared to Chinese adults, supporting the importance of disaggregating Asians when examining microvascular outcomes. Future studies should examine ACEI/ARB use and albuminuria progression. Presentation: Tuesday, June 14, 2022 10:15 a.m. - 10:30 a.m.

High Triglyceride-Glucose Index with Renal Hyperfiltration and Albuminuria in Young Adults: The Korea National Health and Nutrition Examination Survey (KNHANES V, VI, and VIII).

Background: High triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, is associated with an increased risk of albuminuria in adults. However, the relationship between high TyG index associated with renal hyperfiltration (RHF) and albuminuria among young adults is unclear. Methods: A total of 5420 participants aged 19-39 years were enrolled from the Korean National Health and Nutrition Examination Survey (2011-2014 and 2019) and their TyG index levels were analyzed. RHF was defined as eGFR with residuals > 90th percentile after adjusting for age, sex, weight, and height. Albuminuria was defined as urinary albumin-to-creatinine ratio ≥ 30 mg/g Cr. Logistic regression analyses were used to evaluate the association between TyG index, RHF, and albuminuria. Results: The mean age was 30.7 ± 6.0 years and 46.4% were male. The prevalence of albuminuria and RHF was higher in the higher tertiles of TyG index. In our multivariable model, high TyG index showed higher risk of albuminuria (odds ratio (OR) per 1.0 increase in TyG index, 1.56; 95% confidence interval (CI), 1.24-1.95 and OR in the highest tertile, 1.65; 95% CI, 1.08-2.52). High TyG index was associated with higher risk of RHF (OR per 1.0 increase in TyG index, 1.56; 95% CI, 1.32-1.84 and OR in the highest tertile, 1.73; 95% CI, 1.31-2.30). When participants were divided into with or without RHF, high-TyG index-associated high risk of albuminuria was only observed in those with RHF. Participants with concurrent high TyG index and RHF showed the highest risk of albuminuria. Mediation analysis showed that 54.2% of the relation between TyG index and albuminuria was mediated by RHF (95% CI of indirect effect, 0.27-0.76). Finally, incorporating TyG index into our basic model improved the predictive value for albuminuria only in participants with RHF. Conclusion: High TyG index associated with RHF was the strongest risk factor for albuminuria in this study. Early identification of high TyG index with RHF may prevent future development of CKD in relatively healthy and young adults.

Renal Amyloidosis: Epidemiological, Clinical, and Laboratory Profile in Adults from One Nephrology Center.

Background Renal amyloidosis is one of the main differential diagnoses of nephrotic proteinuria in adults and the elderly. The aim of this study with the most important series in our country is to contribute to the epidemiological, clinical, and etiological study of the renal amyloidosis. Methods In a retrospective study carried out between 1975 and 2019, 310 cases of histologically proven and typed renal amyloidosis were selected for this study. Results There were 209 men and 101 women with a mean age of 53.8 ± 15.4 years (range, 17–84 years). Of the 310 cases, 255 (82.3%) were diagnosed with AA renal amyloidosis and 55 (17.7%) with non-AA amyloidosis. Infections were the main cause of AA amyloidosis, and tuberculosis was the most frequent etiology. The period from the onset of the underlying disease to diagnosis of the renal amyloidosis was an average of 177 months. The most frequent manifestations at the time of diagnosis were nephrotic syndrome (84%), chronic renal failure (30.3%), and end-stage renal disease (37.8%). After a medium follow-up of 16 months (range, 0–68 months), mortality occurred in 60 cases. Conclusions Given the high frequency of AA amyloidosis in our country, awareness of the proper management of infectious and chronic inflammatory diseases remains a priority in reducing the occurrence of this serious disease.

First Drug to Reduce Proteinuria in Berger's Disease.

Budesonide (Tarpeyo) has received accelerated approval to reduce proteinuria in adults with primary immunoglobulin A nephropathy, also known as Berger's disease.Nurses should assess if any coprescribed drugs could induce a drug-drug interaction via the cytochrome P-450 isoenzyme system. Because budesonide causes immunosuppression, patients are at high risk for developing infections and should be told to avoid anyone who is known to have an infection.