Baseline Proteinuria Research Articles

#4764 NEPHROTIC SYNDROME IN PREGNANT DIABETIC WOMEN: MATERNAL AND PERINATAL OUTCOMES AT A TERTIARY CENTER

Abstract Background and Aims Management of pregnant women with diabetic kidney disease and nephrotic range proteinuria or nephrotic syndrome constitute a challenge to clinicians. Maternal and perinatal outcomes, especially in patients with chronic kidney disease, remain poor. The authors describe the multidisciplinary approach and the outcomes of diabetic pregnant patients with nephrotic range proteinuria. Method Retrospective observational study in which the authors reviewed maternal, obstetric and perinatal outcomes in pregnant diabetic woman with nephrotic range proteinuria or nephrotic syndrome surveilled at our nephro-obstetric unit from 2011 until 2021. Results We evaluated 7 gestations in 6 patients. Mean age was 31.7±4.7 years (26-38), 5 were caucasian and 1 was black African, and 4 were nuliparas. They all had type 1 diabetes, with mean disease diagnosis at 9.9±5.9 years of age. All patients had chronic hypertension and 5/6 patients had poor glycemic control before pregnancy (mean HbA1c of 11.9%). Mean baseline SCr was 1.1±0.5 mg/dl (0.51-2.8) and mean baseline proteinuria was 3697.2±2301.4 mg/day (75-6326), with 1/1/3/2 patients being on CKD stage 1/2/3/4, before pregnancy, respectively. Exposure to teratogenic therapy during the first trimester occurred in 5/7 gestations with a mean exposure of 7.4 ± 3.1 weeks. Proteinuria increased in all patients and renal function deteriorated in 5/7 gestations (mean SCr of 2.5±1.2; 0.67-4.07 mg/dl) in association with pre-eclampsia in 2 patients and with pregnancy hyperfiltratrion and nephrotic syndrome in all gestations. One patient started dialysis at week 28, due to urea levels >100mg/dL. Partial renal recovery occurred in 2 patients. To date, 3/6 patients initiated PD 15 months (6-29 months) after gestation, 1 of which received a kidney-pancreas transplant. Hypertension aggravated in 6 gestations. Aspirin and low molecular weight heparin were initiated in 6 gestations and they were all treated with furosemide to control volume overload. Regarding fetal outcomes, severe fetal growth restriction was responsible for 1 still birth and 1 medical termination of pregnancy, both at 24 weeks. Cesarean was performed in 4/5 gestations (one is still undergoing) due to pre-eclampsia, renal function deterioration and/or fetal growth restriction. Mean gestation age at delivery was 29.5±4.7 weeks, mean birth weight was 1389 ±203.3 mg (1190-1665) and mean apgar scores at 1/5/10 minutes were 9/10/10 respectively. Neonatal intensive care was needed in 4 newborns. Conclusion This study reinforces the idea that diabetic women with nephrotic range proteinuria have an increased risk of complications and worse outcomes during pregnancy, namely pre-eclampsia, fetal growth restriction, preterm delivery and renal function deterioration. As such, glycemic and proteinuric control should be optimized and careful counseling regarding outcomes should be discussed before pregnancy. Management during gestation should involve an experienced multidisciplinary team including endocrinologist, nutritionist, nephrologist and obstetrician.

#6899 MICROVASCULAR LESIONS IN LUPUS NEPHRITIS

Abstract Background and Aims Microvascular lesions (MVL) can be found in the kidneys of lupus nephritis (LN) patients and might be associated with worse outcomes. There are very few studies which evaluated MVLs in these patients and we aimed to provide a comprehensive evaluation of all MVLs, their frequency, characteristics and association with renal outcomes one year after kidney biopsy. Method We have conducted a retrospective cohort study to evaluate the characteristics and prognostic significance of MVLs in the kidney of subjects with LN. We have collected data on demographics, clinical and laboratory parameters and histopathology (light, immunofluorescent and electron microsopy). MVLs were characterized according to previous classifications. SLE was diagnosed using the American College of Rheumatology criteria. Results A total of 56 patients with biopsy-proven LN were followed up for at least one year after kidney biopsy (79% women, mean age at biopsy 38±13 years). Forty patients (71%) had MVLs in the kidney. The most common MVLs were arteriolar endotheliocyte swelling (54%), arteriolar hyalinosis (25%) and endothelialitis (8%) and the frequency distribution of all microvascular lesions is shown in Figure. Median number of lesions in the MVL group was 1 (interquartile range 1 to 2) and subjects had up to 6 MVLs. There was no difference in the median number of MVLs across LN classes (p>0.05). Proteinuria was highest in class V (5.5 g/day, p = 0.06 vs. all other classes). Subjects with MVLs had lower baseline proteinuria compared with those with no lesions (3.6 vs. 5.4 g/day, p = 0.037), but there was no difference in serum creatinine (92 vs. 119 umol/L, p = 0.25). There were no differences in the occurrence or number of MVLs across LN classes (p = 0.63). The number of MVLs was not correlated with proteinuria (p>0.05). There was no difference in the frequency of proliferative lupus between MVL and no MVL groups (79% vs. 60%, p = 0.15). A total of 48% of subjects achieved complete response (CR), 27% achieved partial response (PR) and 25% had no response (NR). MVLs were not associated with response (defined as CR or PR) in a multivariate regression model (OR 3.5 [0.5, 24.6]). Conclusion MVLs are common in LN. They were associated with lower baseline proteinuria, but not with proliferative LN or renal outcomes. The association with proteinuria warrants further research.

#6905 PREVALENCE OF ANTIPLA2R ANTIBODIES IN EGYPTIAN PATIENTS WITH NEPHROTIC SYNDROME

Abstract Background and Aims Primary membranous nephropathy (PMN), a common form of the nephrotic syndrome, is an antibody-mediated autoimmune glomerular disease. Autoimmunity is driven by circulating autoantibodies that bind to one or more antigens on the surface of glomerular podocytes. PLA2R antigen is the most common and prevalent one among these antigens. Anti-PLA2R antibodies are measured in serum and detected within biopsies of primary membranous nephropathy patients. Up to the moment, no clear data about the prevalence of AntiPLA2R antibodies associated PMN in Egyptian patients. The aim of this work was to study the prevalence of antiPLA2R antibodies in Egyptian patients with nephrotic syndrome underwent renal biopsy. Method In this cross-sectional study we recruited 70 adult patients presented with nephrotic range proteinuria to Ain-shams university hospital and a private nephrology center in Cairo during a period of 20 months (from March 2020 to October 2021). All patients first presentation for whom laboratory investigations including serum anti-PLA2R antibodies titer by indirect immunofluorescence and kidney biopsy were done. Anti-PLA2R antibodies were measured in serum, checked in biopsies and correlated with biopsy findings. Results Membranous nephropathy (primary and secondary) was found by biopsy finding in 25 of 70 patients (35.7%) presenting with nephrotic range proteinuria. 21 patients (84%) of the cases of membranous nephropathy had been diagnosed with primary membranous nephropathy and 4 (16%) had been diagnosed with secondary membranous nephropathy. Circulating anti-PLA2R antibodies were detected within serum in 9 (42.85%) of primary MN cases while detection of anti-PLA2R antibodies within the glomerular extracts of primary MN cases was much higher; 17 patients (80.95%). There was positive correlation between serum AntiPLA2R Antibodies titer and U PCR (r = 0.839, P = 0.005) (Fig. 1). Conclusion A we may conclude that, most patients with primary membranous nephropathy have anti-PLA2R antibodies. Detection of anti-PLA2R antibodies within the biopsy has higher sensitivity than serum (80.95% versus 42.85%). Specificity of PLA2R to primary membranous nephropathy is 100%. Patients with high anti-PLA2R titer had higher baseline proteinuria than patients with lower anti-PLA2R titer.

#4613 PREVALENCE OF DKD RAPID PROGRESSION IN TYPE 2 DIABETES IN A DEVELOPING COUNTRY AND ITS CLINICAL PREDICTORS: A SINGLE CENTERED RETROSPECTIVE STUDY

Abstract Background and Aims A significant proportion of diabetic kidney patients experience a rapid decline in GFR, leading to ESRD within months. Although there is a large number of studies on DKD, at present, there is a lack of well-controlled long follow-up studies to assess the burden of rapid progression, distinguishing the clinical profile of rapid progressors from non-progressors and its predictors. Identifying independent risk factors that contribute specifically to rapid progression is essential to prevent end-stage renal disease. Here we conducted a retrospective, hospital-based cohort study aimed to assess the prevalence, clinical profile, and clinical predictors for the rapid progression of DKD in type 2 DM. Method Type 2 DKD patients attending tertiary care hospital in South India were involved between January 2018 and 2022. CKD5 and those without minimum 6 months follow-up were excluded. Patients were followed up for 3.5 years. A sustained decline of eGFR >10 mL/1.73 m2/year was defined as rapid progressors. Patients were categorized into rapid and non-rapid progressors. Clinical profiles, micro-macrovascular complications, cardiovascular events, and other risk factors for rapid progression were studied. Data were analyzed using SPSS22 Results In a median follow-up of 3.5 years, 220(61.3%) were rapidly progressed with median eGFR decline 12ml/1.73 m2/year(IQR 8.5-19.3), and 139(38.7%) were non-rapid progressors with median eGFR decline 1.6ml/1.73 m2(IQR-0-3.3).The baseline characteristics were given in Table 1. The presence of hypertension, proteinuria, diabetic retinopathy, and cardiovascular events (p-0.01) was higher in rapid progressors than non-progressors.On logistic regression analysis, independent predictors of rapid progression were proteinuria (OR4.7;95%CI(2.24-9.88); P = .001), diabetic retinopathy(OR 0.24; 95% CI(0.11-0.52); P = .001), and AKI episodes(OR 2.18;95% CI (1.28-3.71); P = .003) (Table 2). Conclusion The majority of type 2 DKD patients in our setting are rapid progressors. The higher degree of baseline proteinuria, presence of diabetic retinopathy, and AKI episodes were found independently associated with clinical predictors of progression.

#3032 EFFICACY AND SAFETY OF VOCLOSPORIN IN PATIENTS WITH PROTEINURIA ≥2 MG/MG: AN INTEGRATED ANALYSIS OF THE AURA-LV AND AURORA 1 STUDIES

Abstract Background and Aims Proteinuria has been established as a mediator of progressive renal damage in many nephropathies. However, recent studies of several monoclonal antibodies demonstrated a lack of efficacy in patients with lupus nephritis and moderate to high levels of proteinuria (UPCR ≥2 to ≥3 mg/mg), potentially due to an increase in renal antibody clearance.1-4 Given that, we examined the efficacy and safety of voclosporin in patients with lupus nephritis and a UPCR of ≥2 mg/mg using the pooled dataset from the Phase 2 AURA-LV and Phase 3 AURORA 1 trials. Method Both studies enrolled patients with biopsy-proven LN (Class III, IV, or V ± III/IV, biopsied within 6 months in AURA-LV or up to 2 years in AURORA 1) and proteinuria ≥1.5 mg/mg (≥2 mg/mg for Class V). Patients were randomized to receive either voclosporin (23.7 mg BID) or placebo and treated for up to one year (48 weeks [AURA-LV], 52 weeks [AURORA 1]); all patients received MMF and low-dose steroids. For this post-hoc analysis, changes in UPCR and renal response rates were evaluated in patients with baseline UPCR ≥2 mg/mg. Complete renal response (CRR) was defined as UPCR ≤0.5 mg/mg with stable renal function, low-dose steroids, and no rescue medication; partial renal response (PRR) was defined as a ≥50% reduction in UPCR from baseline. Safety outcomes were also assessed. Results The pooled analysis included 268 and 266 patients in the voclosporin and control arms, respectively. Of those, 217 and 215 patients had UPCR ≥2 mg/mg (baseline mean [SD], 5.2 [3.4] vs. 4.6 [2.9] mg/mg, respectively). A significantly greater percentage of voclosporin-treated patients achieved a CRR at one year compared to the control arm (41.0% vs. 21.9%; odds ratio [OR] 2.48, p<0.0001, Figure 1A). Similarly, significantly more patients in the voclosporin arm (69.6%) than control arm (50.0%) achieved a PRR at the same time point (OR 2.3, p<0.0001); this endpoint was met significantly earlier in voclosporin-treated patients as well (29 vs. 57 days, hazard ratio [HR] 2.0, p<0.0001). The median time to UPCR ≤0.5 mg/mg was also significantly earlier in the voclosporin arm (211 days); less than 50% of the control arm achieved this endpoint within the study period (OR 1.9, p<0.0001, Figure 1B). Adverse event rates were comparable in both arms (Table 1), and mean eGFR levels were similar and stable over the study period, a trend that was maintained for AURORA 1 patients who continued randomized treatment for another two years in the AURORA 2 study. Conclusion Consistent with results from the overall pooled study population, patients with UPCR ≥2 mg/mg at baseline treated with voclosporin achieved significantly higher renal response rates and significantly earlier reductions in UPCR than patients treated with MMF and low-dose steroids alone. These findings are clinically important given the lack of effective therapies available for patients with high baseline proteinuria.

#4590 A PROSPECTIVE STUDY OF EPLERENONE IN THE TREATMENT OF PATIENTS WITH GLOMERULONEPHRITIS

Abstract Background and Aims Clinical evidence suggests that high aldosterone plasma levels contributes to progressive kidney disease. Although administration of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin type 1 receptor blockers (ARB) can delay kidney disease progression, plasma aldosterone levels may increase to a significant extent even after the initiation of such treatment. Thus, administration of mineralocorticoid receptor antagonists such as spironolactone, on top of treatment with ACEi or ARBs has been shown to reduce albuminuria and slow down kidney function deterioration. Nevertheless, there is scanty evidence on the effect of eplerenone in patients with kidney disease due to glomerulonephritis. Method In this prospective open-label study, we evaluated the effects of eplerenone in patients with biopsy proven glomerulonephritis already treated with ACEi or ARBs. Patients were divided in the active treatment arm, who received 25 mg of eplerenone daily besides ACEi or ARBs, and a control group that received only standard treatment. Protein excretion in 24 h urine, eGFR, blood pressure and serum K+ levels were measured at 3, 6 and 12 months after study initiation. Results Out of 83 patients who were screened, 62 patients were included in the final analysis. Twenty-six received eplerenone and 36 were treated with ACEi (25) or ARBs (9) alone (controls). After 1 year of treatment with eplerenone, proteinuria decreased from 1597 to 1145 mg/24 h while it did not alter in controls. Eplerenone reduced proteinuria especially in those with baseline proteinuria of >1000 mg/24 h. Kidney function remained stable in patients treated with eplerenone (from eGFR: 82.51±22.6 to 84.68±31.7 ml/min/1.73 m2, p = 0.8) and showed a non significant deterioration in controls (from eGFR: 68.39±26.2 to 66.63±29.8 ml/min/1.73 m2, p = 0.08). Systolic blood pressure was significantly reduced in the active treatment arm (from 128.1±17.5 to 126.3±10.93 mmHg, p = 0.03), whereas eplerenone did not increase serum K+ levels or had any other significant adverse effect. Conclusion Administration of eplerenone at a dose of 25 mg/day, on top of treatment with ACEi or ARBs, can further reduce proteinuria and systolic blood pressure in patients with chronic glomerulonephritis.

Impact of Renal Function on the Prognosis of Patients Receiving Atezolizumab/Bevacizumab Combination Therapy and Lenvatinib Monotherapy for Unresectable Hepatocellular Carcinoma

Introduction: Several studies have reported kidney injury caused by immune checkpoint inhibitors, and proteinuria caused by vascular endothelial growth factor inhibitors for unresectable hepatocellular carcinoma (u-HCC). We investigated the relationship between renal function and prognosis in patients with u-HCC receiving atezolizumab and bevacizumab (AB) and lenvatinib (LEN) therapy. Methods: Fifty-one patients who received AB and 50 patients who received LEN therapy were included. We analyzed prognostic factors related to the overall survival (OS), and characteristics related to renal function. Results: In patients with AB therapy, OS was shorter in patients with baseline proteinuria of 1+ or higher, as assessed by urine dipstick test, compared to those with –/± (p = 0.024). There were many cases with two or more drugs with a high risk of renal dysfunction (p = 0.019) in patients with 1+ or higher. Furthermore, OS was shorter in the group with estimated glomerular filtration rate (eGFR) grade deterioration without urinary protein-creatinine ratio (UPCR) of 2 g/g·Cre or higher than in the other groups (p = 0.027). In the group where eGFR worsened without an increase in UPCR, there were many cases with a daily salt intake of 10 g or more (p = 0.027), three or more drugs with a high risk of renal dysfunction (p = 0.021), and a history of arteriosclerosis (p = 0.021). On the other hand, in patients with LEN therapy, OS tends to be shorter in patients with proteinuria of ± or higher, compared to those without (p = 0.074). There were many cases with a daily salt intake of 10 g or more in patients with ± or higher (p = 0.002). Conclusion: In patients receiving AB and LEN therapy, baseline proteinuria was associated with OS. Renal function deterioration without proteinuria was associated with a poor prognosis in AB therapy. Excessive salt intake, preexisting atherosclerotic disease, and drug with a high risk of renal dysfunction were risk factors for renal deterioration.

Diagnostic and prognostic performance of renal compartment volume and the apparent diffusion coefficient obtained from magnetic resonance imaging in mild, moderate and severe diabetic kidney disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD). There are unmet needs for noninvasive diagnosis and prognosis prediction of DKD in clinical practice. This study examines the diagnostic and prognostic value of magnetic resonance (MR) markers of renal compartment volume and the apparent diffusion coefficient (ADC) for mild, moderate, and severe DKD. This study was registered at the Chinese Clinical Trial Registry Center (registration number: ChiCTR-RRC-17012687). Sixty-seven DKD patients were prospectively randomly enrolled and underwent clinical examination and diffusion-weighted magnetic resonance imaging (DW-MRI). Patients with comorbidities that affected renal volumes or components were excluded. Ultimately, 52 DKD patients were included in the cross-sectional analysis. The ADC in the renal cortex (ADCcortex), ADC in the renal medulla (ADCmedulla) and difference between ADCcortex and ADCmedulla (ΔADC) were measured using a twelve-layer concentric objects (TLCO) approach. Renal compartment volumes of the parenchyma and pelvis were derived from T2-weighted MRI. Due to lost contact or ESRD diagnosed before follow-up (n=14), only 38 DKD patients remained for follow-up (median period =8.25 years) to investigate the correlations between MR markers and renal outcomes. The primary outcomes were the composite of doubling of the primary serum creatinine concentration or ESRD. ADCcortex presented superior performance in discriminating DKD with normal and declined estimated glomerular filtration rate (eGFR) over ADCmedulla, ΔADC and renal compartment volumes with an AUC of 0.904 (sensitivity of 83% and specificity of 91%) and was moderately correlated with the clinical biomarkers eGFR and proteinuria (P<0.05). The Cox survival analysis demonstrated that ADCcortex rather than ΔADC is a predictor of renal outcomes with a hazard ratio of 3.4 (95% CI: 1.1-10.2, P<0.05) independent of baseline eGFR and proteinuria. ADCcortex is a valuable imaging marker for the diagnosis and prediction of renal function decline in DKD.

Epidemiology and outcomes of post-AKI proteinuria.

Acute kidney injury (AKI) has been associated with increased risks of new-onset and worsening proteinuria. However, epidemiologic data for post-AKI proteinuria was still lacking. This study aimed to determine the incidence, risk factors and clinical correlations of post-AKI proteinuria among hospitalized patients. This study was conducted in a multicenter cohort including patients aged 18-100 years with hospital-acquired AKI (HA-AKI) hospitalized at 19 medical centers throughout China. The primary outcome was the incidence of post-AKI proteinuria. Secondary outcomes included AKI recovery and kidney disease progression. The results of both quantitative and qualitative urinary protein tests were used to define post-AKI proteinuria. Cox proportional hazard model with stepwise regression was used to determine the risk factors for post-AKI proteinuria. Of 6206 HA-AKI patients without proteinuria at baseline, 2102 (33.9%) had new-onset proteinuria, whereas of 5137 HA-AKI with baseline proteinuria, 894 (17.4%) had worsening proteinuria after AKI. Higher AKI stage and preexisting CKD diagnosis were risk factors for new-onset proteinuria and worsening proteinuria, whereas treatment with renin-angiotensin system inhibitors was associated with an 11% lower risk of incident proteinuria. About 60% and 75% of patients with post-AKI new-onset and worsening proteinuria, respectively, recovered within 3 months. Worsening proteinuria was associated with a lower incidence of AKI recovery and a higher risk of kidney disease progression. Post-AKI proteinuria is common and usually transient among hospitalized patients. The risk profiles for new-onset and worsening post-AKI proteinuria differed markedly. Worsening proteinuria after AKI was associated with adverse kidney outcomes, which emphasized the need for close monitoring of proteinuria after AKI.

Kidney Disease Patient Representation in Trials of Combination Therapy With VEGF-Signaling Pathway Inhibitors and Immune Checkpoint Inhibitors: A Systematic Review

Kidney Disease Patient Representation in Trials of Combination Therapy With VEGF-Signaling Pathway Inhibitors and Immune Checkpoint Inhibitors: A Systematic Review

Factors Affecting Kidney Functions in One-Year Follow-up After COVID-19 in Kidney Transplant Patients

Background Coronavirus disease (COVID-19) is more severe, and mortality is higher in kidney transplantation (KTx) patients; it is still unclear how renal functions progress and the conditions affecting renal functions in the post-COVID-19 period. We aimed to investigate the changes in kidney functions and the factors affecting this change after COVID-19.&#x0D; Material and Methods Forty-one kidney transplantation patients who were hospitalised for COVID-19 were included in this retrospective study. The patient's personal information, examination, and treatment information regarding their hospitalisation and follow-ups were obtained from the hospital system.&#x0D; Results Patients with elevated serum creatinine in the first year post-COVID had higher baseline proteinuria and systemic immune inflammation index (SII). Proteinuria increased more in patients with a long transplantation period, hypertension, high basal creatinine, and SII. Also, proteinuria was higher in patients who developed AKI during the COVID period. In addition, baseline SII was an independent predictor of the change in serum creatinine and proteinuria.&#x0D; Conclusions We found that patients with signs of increased inflammation, such as high SII were more fragile regarding renal functions. Therefore, the post-COVID-19 follow-up process of KTx patients with COVID-19 should be individualised.

Impact of Baseline Clinical Variables on SGLT2i's Antiproteinuric Effect in Diabetic Kidney Disease.

Proteinuria is a major risk factor for the progression of chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) demonstrated a nephroprotective and antiproteinuric effect in people with type 2 diabetes (T2DM) and proteinuric CKD. We conducted a retrospective study to evaluate clinical and laboratory variables that can help predict proteinuria reduction with SGLT2i therapy. Patients affected by T2DM and CKD who started any SGLT2i were included in the study. Patients were stratified into two subgroups, Responder (R) and non-Responder (nR), based upon the response to the therapy with SGLT2i, namely the reduction in a 24 h urine proteins test (uProt) of ≥30% from baseline levels. The aim of the study is to analyse differences in baseline characteristics between the two groups and to investigate the relationship between them and the proteinuria reduction. A Kruskal-Wallis test, unpaired t-test and Chi2 test were used to test the difference in means and the percentage (%) between the two groups. Linear and logistic regressions were utilized to analyse the relationship between proteinuria reduction and basal characteristics. A total of 58 patients were enrolled in the study: 32 patients (55.1%) were in the R group and 26 patients (44.9%) in the nR group. R's patients had a significant higher uProt at baseline (1393 vs. 449 mg/24 h, p = 0.010). There was a significant correlation between baseline uProt and proteinuria reduction with SGLT2i in both univariate (β = -0.43, CI -0.55 to -031; p < 0.001) and multivariate analyses (β = -0.46, CI -0.57 to -0.35, p < 0.001). In the multivariate analysis, there was a significant positive correlation between the estimated glomerular filtration rate (eGFR) and proteinuria reduction (β = -17, CI -31 to -3.3, p = 0.016) and a significant negative correlation with body mass index (BMI) (β = 81, CI 13 to 50, p = 0.021). The multivariate logistic regressions show a positive correlation of being in the R group with diabetic retinopathy at baseline (Odds Ratio (OR) 3.65, CI 0.97 to 13.58, p = 0.054), while the presence of cardiovascular disease (CVD) at baseline is associated with being in the nR group (OR 0.34, CI 0.09 to 1.22, p = 0.1), even if these statements did not reach statistical significance. In this real-life experience, following the administration of SGLT2i, a reduction of more than 30% in proteinuria was observed in more than half of the patients, and these patients had a significantly higher baseline proteinuria value. Variables such as eGFR and BMI are variables that, considered in conjunction with proteinuria, can help predict treatment response before therapy initiation. Different phenotypes of diabetic kidney disease may have an impact on the antiproteinuric response.

Associations between eGFR and albuminuria with right ventricular measures: the MESA-Right Ventricle study.

Chronic kidney disease (CKD) is associated with an increased risk of pulmonary hypertension, which may lead to right ventricular (RV) pressure overload and RV dysfunction. However, the presence of subclinical changes in RV structure or function in early CKD and the influence of these changes on mortality are not well studied. We hypothesized that early CKD, as indicated by elevated albuminuria or mild reductions in estimated glomerular filtration rate (eGFR), is associated with greater RV dilation and RV mass. We included 4063 participants (age 45-84years) without baseline clinical cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis. The associations of baseline creatinine-cystatin C-based eGFR and albuminuria with cardiac magnetic resonance-derived RV measures (2000-02) were examined cross-sectionally with linear regression models. Cox regression models were used to examine whether RV parameters modified the associations of eGFR and albuminuria with all-cause mortality. Participants with reductions in eGFR primarily within the 60-89mL/min/1.73 m2 category had smaller RV end-diastolic and end-systolic volumes and stroke volume (all adjusted P-trends <.001) than those with eGFR ≥90mL/min/1.73 m2, an association that was predominantly seen in participants with albuminuria below 30mg/g creatinine. Albuminuria was more strongly associated with death among those with lower RV volumes (P-values for interaction <.03). Among community-dwelling adults, reductions in eGFR primarily within the normal range were associated with smaller RV volumes and the association of albuminuria with worse survival was stronger among those with smaller RV volumes. Further studies are needed to elucidate the underlying mechanistic pathways that link kidney measures and RV morphology.

Twenty-four-hour proteinuria levels are associated with adverse pregnancy outcomes among women with CKD.

Proteinuria is commonly measured to assess the renal status of chronic kidney disease (CKD) patients before the 20th week of gestation during pregnancy. High levels of proteiuria have been associated with adverse pregnancy outcomes. However, researchers have not clearly determined what baseline proteinuria levels would be associated with adverse pregnancy outcomes. This study aimed to analyse associations between proteinuria levels and adverse pregnancy outcomes among CKD patients treated with or without steroids/immunosuppressive therapy in early pregnancy. This retrospective study included the clinical information of 557 pregnant patients with CKD from 1 January 2009 to 31 December 2021. A multivariable logistic regression analysis was conducted to evaluate the risk of adverse pregnancy outcomes across various proteinuria ranges, which were further stratified by whether the patients were receiving steroids/immunosuppressive therapy. (i) Proteinuria was assessed on 24-h urine collection. The median (quartile) baseline proteinuria levels were 0.83g (0.20, 1.92) and 0.25g (0.06, 0.80) in the steroids/immunosuppressive therapy and therapy-free groups, respectively. (ii) CKD patients with adverse pregnancy outcomes had significantly higher proteinuria levels in the first trimester than patients without adverse pregnancy outcomes. (iii) The risk of adverse pregnancy outcomes increased with increasing baseline proteinuria levels (P<.001). (iv) In the early-pregnancy steroids/immunosuppressive therapy group, the risk of severe preeclampsia was higher in patients with higher baseline proteinuria levels (P<.007) [odds ratio (OR) 30.86 for proteinuria ≥5.00g/24h]; in the therapy-free group, the risks of severe preeclampsia, very-low-birth-weight infants, early preterm birth and foetal-neonatal death were higher in patients with higher baseline proteinuria levels (OR 53.16 for proteinuria ≥5.00g/24h; OR 37.83 for proteinuria ≥5.00g/24h; OR 15.30 for proteinuria ≥5.00g/24h; and OR 18.83 for proteinuria ≥5.00g/24h, respectively; P<.001, P<.001, P<.001 and P=.006, respectively). As shown in the present study, a baseline 24-h proteinuria level >1.00g was associated with adverse maternal outcomes. Furthermore, a 24-h proteinuria level >2.00g increased the incidence of adverse foetal events among CKD patients.

Triglycerides and Renal Outcomes According to Albuminuria and in Consideration of Other Metabolic Syndrome Components in Diabetic US Veterans

Introduction: Hypertriglyceridemia, a component of the metabolic syndrome, is a known independent predictor of albuminuria and chronic kidney disease (CKD) in the general population. Previous studies have shown that the relationship of triglycerides (TGs) with outcomes changes across stages of CKD. Our objective was to examine the association of TG independent of other metabolic syndrome components with renal outcomes in diabetic patients with or without CKD. Methods: This retrospective cohort study included diabetic US veteran patients with valid data on TGs, estimated glomerular filtration rate (eGFR), and albuminuria (urinary albumin/creatinine ratio) between fiscal years 2004 and 2006. Using Cox models adjusted for clinical characteristics and laboratory markers, we evaluated the relationship of TG with incident albuminuria (stratified by eGFR category) and based on eGFR (stratified by baseline albuminuria categories). To evaluate the relationship of TG with time to end-stage renal disease (ESRD), we stratified models by baseline CKD stage (eGFR category) and baseline albuminuria stage ascertained at time of TG measurement. Results: In a cohort of 138,675 diabetic veterans, the mean ± SD age was 65 ± 11 years old and included 3% females and 14% African Americans. The cohort also included 28% of patients with non-dialysis-dependent CKD (eGFR <60 mL/min/1.73 m²), as well as 28% of patients with albuminuria (≥30 mg/g). The median (IQR) of serum TG was 148 (100, 222) mg/dL. We observed a slight positive linear association between TG and incident CKD after adjustment for Case-Mix and Laboratory variables among non-albuminuric and microalbuminuric patients. The relationship of high TG trended towards a higher risk of ESRD in CKD 3A non-albuminuric patients and in CKD 3A and 4/5 patients with microalbuminuria. Conclusion: In a large cohort, we have shown that elevated TGs are associated with all kidney outcomes tested independently of other metabolic syndrome components in diabetic patients with normal eGFR and normal albumin excretion rate, but the association is weaker in some groups of diabetic patients with preexisting renal complications.

Association of urinary liver-type fatty acid-binding protein with renal functions and antihyperglycemic drug use in type 2 diabetic nephropathy patients.

In diabetic nephropathy exacerbation, a reduction in the estimated glomerular filtration rate (eGFR) without raised albuminuria or proteinuria has been frequently observed. This study aimed to clarify the clinical usefulness of urinary liver-type fatty acid-binding protein (L-FABP) in the exacerbation of diabetic nephropathy in type 2 diabetes. A cross-sectional study and a retrospective observational study of 227 patients with type 2 diabetes were conducted to investigate the relationship between urinary L-FABP and renal dysfunction. Changes in urinary L-FABP with or without additional administration of antihyperglycemic drugs were examined in 63 patients. Baseline urinary L-FABP was significantly associated with baseline eGFR (ρ = -0.34, p < 0.001) and baseline albuminuria (ρ = 0.64, p < 0.001). In multivariate regression analysis, baseline urinary L-FABP was a significant independent factor for eGFR reduction [β = -0.348, 95% confidence interval (CI) = -0.482 to -0.214, p < 0.001]. Cox regression analysis showed that patients with a baseline urinary L-FABP above 6.5μg/g creatinine exhibited a higher hazard ratio (HR) for the renal dysfunction surrogate end point (HR = 15.00, 95% CI 3.640-61.40, p < 0.001). In logistic regression analysis, administration of sodium glucose cotransporter-2 inhibitors was associated with a statistically significant reduction in urinary L-FABP levels, independent of changes in systolic blood pressure, glycosylated hemoglobin, and eGFR (odds ratio = 0.75, 95% CI 0.56-0.99, p = 0.04). Urinary L-FABP may be associated with the future decrease in renal functions in type 2 diabetic nephropathy patients. Additionally, urinary L-FABP could be used as a marker of the effectiveness of diabetic nephropathy treatment.

The association of plasma NT-proBNP level and progression of diabetic kidney disease

Aims Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease (ESKD). The identification of risk factors involved in the progression of DKD to ESKD is expected to result in early detection and appropriate intervention and improve prognosis. This study aimed to explore whether plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with kidney outcomes in patients with type 2 diabetes mellitus (T2DM) and biopsy-proven DKD. Methods Patients with biopsy-proven DKD who were followed up at West China Hospital over 12 months were enrolled. The kidney outcome was defined as progression to ESKD. The cutoff value of plasma NT-proBNP concentration was calculated by using receiver operating characteristic (ROC) curve analysis. The influence of NT-proBNP levels on kidney outcome in patients with DKD was assessed using Cox regression analysis. Results A total of 30 (24.5%) patients reached ESKD during a median follow-up of 24.1 months. The baseline serum NT-proBNP level had a significant correlation with baseline proteinuria, kidney function, glomerular lesions, interstitial fibrosis tubular atrophy (IFTA), and arteriolar hyalinosis. Multivariate Cox regression analysis indicated that increased NT-proBNP level was significantly associated with a higher risk of progression to ESKD (HR 6.43; 95% CI (1.65–25.10, p = 0.007), and each 1 SD increase in LG (NT-proBNP) was also associated with a higher risk (HR 2.43; 95% CI 1.94–5.29, p = 0.047) of an adverse kidney outcome after adjusting for confounding factors. Conclusions A higher level of plasma NT-proBNP predicts kidney prognosis in patients with biopsy-proven DKD. This warrants further investigation into the potential mechanisms.

Pre-Pregnancy eGFR and the Risk of Adverse Maternal and Fetal Outcomes: A Population-Based Study.

Pregnancies in women with CKD carry greater risk than pregnancies in the general population. The small number of women in prior studies has limited estimates of this risk, especially among those with advanced CKD. We report the results of a population-based cohort study in Ontario, Canada, that assessed more than 500,000 pregnancies, including 600 with a baseline eGFR < 60 ml/min per 1.73 m 2 . The investigation demonstrates increases in risk of different adverse maternal and fetal outcomes with lower eGFR and further risk elevation with baseline proteinuria. CKD is a risk factor for pregnancy complications, but estimates for adverse outcomes come largely from single-center studies with few women with moderate or advanced stage CKD. To investigate the association between maternal baseline eGFR and risk of adverse pregnancy outcomes, we conducted a retrospective, population-based cohort study of women (not on dialysis or having had a kidney transplant) in Ontario, Canada, who delivered between 2007 and 2019. The study included 565,907 pregnancies among 462,053 women. Administrative health databases captured hospital births, outpatient laboratory testing, and pregnancy complications. We analyzed pregnancies with serum creatinine measured within 2 years of conception up to 30 days after conception and assessed the impact of urine protein where available. The risk of major maternal morbidity, preterm delivery, and low birthweight increased monotonically across declining eGFR categories, with risk increase most notable as eGFR dropped below 60 ml/min per 1.73 m 2 . A total of 56 (40%) of the 133 pregnancies with an eGFR <45 ml/min per 1.73 m 2 resulted in delivery under 37 weeks, compared with 10% of pregnancies when eGFR exceeded 90 ml/min per 1.73 m 2 . Greater proteinuria significantly increased risk within each eGFR category. Maternal and neonatal deaths were rare regardless of baseline eGFR (<0.3% of all pregnancies). Only 7% of women with an eGFR <45 ml/min per 1.73 m 2 received dialysis during or immediately after pregnancy. We observed higher rates of adverse pregnancy outcomes in women with low eGFR with concurrent proteinuria. These results can help inform health care policy, preconception counseling, and pregnancy follow-up in women with CKD.

Incident heart failure and the subsequent risk for progression to end stage kidney disease in South East Asian people with type 2 diabetes

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Singapore National Medical Research Council grants: CSA-INV/0020/2017 and CS-IRG (MOH-000066) Background Heart failure (HF) is a common but often unrecognized complication of type 2 diabetes (T2D). Both low eGFR and high albuminuria are strong risk factors for development of HF in diabetic population. However, data on the role of HF in long-term kidney disease outcome are sparse. Aim We sought to study the risk for progression to end stage kidney disease (ESKD) after incident HF in multi-ethnic South East Asian people with type 2 diabetes. Participants and Methods A total of 1,756 individuals with type 2 diabetes recruited from a regional hospital were followed for a median of 7.3 (interquartile range 6.8-7.8) years. Incident HF was identified according to European Society of Cardiology 2016 criteria. HF was subtyped into preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) with ventricular ejection fraction (LVEF) cut-off at ≥50% and &amp;lt;50% respectively. Progression to ESKD was defined as patients with sustained eGFR &amp;lt;15ml/min per 1.73m2 with confirmation measurement 3 months apart, or on sustained dialysis for at least 3 months or death attributable to renal cause, whichever occurred first. The risk of progression to ESKD after HF was assessed using Cox proportional hazard models. Results Average age of participants was 57±11 years with diabetes duration of 11 (IQR 4-15) years. There were 52% Chinese, 22% Malay and 26% Asian Indian in the study participants. We identified 113 incident HF events (65 HFpEF and 48 HFrEF) during 11,869 patient-years (crude incidence rate 9.5 per 1000 patient-years). Individuals with HF occurrence were older, had a longer diabetes duration, higher body mass index, HbA1c and systolic blood pressure, and prevalent diabetic kidney disease (DKD). We identified 75 ESKD events in the follow-up (incidence rate 6.0 per 1000 patient-years) and 22 occurred after incident HF. Cox regression model showed that incident HF was associated with 7.4-fold (95% CI 4.5-12.2) unadjusted risk for progression to ESKD. The association of HF with subsequent risk for ESKD remained statistically significant (adjusted hazard ratio, HR 2.3, 95% CI 1.3-4.2) after adjustment for multiple clinical risk factors including baseline eGFR and albuminuria. Similar outcome was obtained when death attributable to non-renal cause was taken as a competing risk for ESKD. In a fully adjusted model, both HFpEF and HFrEF patients had a higher risk for progression to ESKD (adjusted HR 2.8, 95%CI 1.4-5.9, and 2.2, 95%CI 1.0-4.7, respectively), as compared to those with no HF events. The incidence rate of ESKD in patients with incident HF was 5.6 per 100 patient-years whilst in propensity score-matched patients without HF event, the rate was 2.1 per 100 patient-years. Conclusion Incident HF is a strong independent risk factor for progression to ESKD in individuals with T2D. Our data highlight the importance for prevention, early diagnosis and treatment of HF to improve the renal outcomes in individuals with type 2 diabetes.

Long-term follow-up of an IgA nephropathy cohort: outcomes and risk factors

Aim IgA nephropathy (IgAN), the most common glomerulopathy worldwide and in Uruguay, raised treatment controversies. The study aimed to analyze long-term IgAN outcomes and treatment. Methods A retrospective analysis of a Uruguayan IgAN cohort, enrolled between 1985 and 2009 and followed up until 2020, was performed. The Ethics Committee approved the study. The inclusion criteria were (a) biopsy-proven IgAN; (b) age ≥12 years; and (c) available clinical, histologic, and treatment data. The patients were divided into two groups, with immunosuppressive (IS) or without (NoIS) treatment. Outcomes (end-stage kidney disease/kidney replacement therapy [ESKD/KRT] or all-cause death) were obtained from mandatory national registries. Results The study population included 241 patients (64.7% men), median age 32 (19.5) years, baseline blood pressure <130/80 mmHg in 37%, and microhematuria in 67.5% of patients. Baseline proteinuria, glomerulosclerosis, and a higher crescent percentage were significantly more frequent in the IS group. Proteinuria improved in both groups. Renal survival at 20 years was 74.6% without difference between groups. In the overall population and in the NoIS group, bivariate Cox regression analysis showed that baseline proteinuria, endocapillary hypercellularity, tubule interstitial damage, and crescents were associated with a higher risk of ESKD/KRT or death, but in the IS group, proteinuria and endocapillary hypercellularity were not. In the multivariate Cox analysis, proteinuria in the NoIS group, crescents in the IS group and tubule interstitial damage in both groups were independent risk factors. Conclusion The IS group had more severe risk factors than the NoIS group but attained a similar outcome.