Higher Proteinuria Research Articles

#4489 EFFECT OF RENAL ARTERY CALCIFICATION ON THE OCCURRENCE OF ACUTE KIDNEY INJURY AND MORTALITY

Abstract Background and Aims Renal artery stenosis not only causes secondary hypertension and drug-resistant hypertension by enhancing renin-angiotensin-aldosterone system (RAAS), but also causes ischemic acute/chronic kidney injury by impeding blood flow to the kidneys. Renal artery calcification (RAC) suggests chronic severe atherosclerotic changes, but the relationship between its severity and clinical prognosis has not been established. Method This study was conducted on subjects aged 60 years or older who had serum creatinine measured more than 3 times among patients prescribed and performed abdominal CT at Chung-Ang University Hospital from January 1, 2005 to February 28, 2020. The renal artery calcification score (RACS) was obtained by Agatston score measurement, and the incidence of AKI and mortality were compared between the groups. Results Of a total of 29,410 patients, 17,478 had no RAC and 11,932 was RAC (+). The median value of the group in which RACS was measured was 117.8. The prevalence and history of diabetes mellitus (DM), hypertension, dyslipidemia, and history of cardiovascular disease were significantly higher in the RAC (+) group, lower eGFR and higher proteinuria, and higher prescribing rates of ARB or ACEi, spironolactone, and statin. In the group of RAC (+), the incidence of AKI (HR 1.231, CI 1.174-1.292, P<0.001, Figure1) and all-cause mortality (HR 1.265, CI 1.182-1.355, P<0.001) was high. Regardless of DM or RACS, the risk of AKI was higher in those who were prescribed ACEi or ARB (HR 1.786, CI 1.7-1.875, P<0.001). In patients with DM, mortality risk was reduced in those taking ACEi or ARB regardless of the presence of RACS (HR 0.759, CI 0.645-0.892, P<0.001). Conclusion RAC(+) was associated with higher AKI and mortality risk than RAC(-). The use of RAAS blockades increased the risk of AKI regardless of the presence of RAC, but reduced mortality in patients with DM regardless of the presence or absence of RACS.

#3053 CORRELATION OF SYSTEMIC AND IN SITU BIOMARKERS OF COMPLEMENT ACTIVATION WITH HISTOPATHOLOGICAL FEATURES AND PROGNOSIS IN C3 GLOMERULOPATHY

Abstract Background and Aims C3 glomerulopathy is a rare complement mediated disease, resulting from complement alternative pathway (AP) activation. In addition to AP activation, there are emerging evidence for terminal pathway (TP) implication in kidney damage. A C3G histopathologic index has recently been proposed to evaluate both activity and chronicity parameters. Only a chronicity index > 4 has been independently validated as prognosis factor for end stage kidney disease. We aimed to determine the impact of local activation of the TP on disease phenotype. Method C3G histopathological index grading were evaluated via central review of 53 kidney biopsies from 43 patients carrying C3G. C5b-9 staining was performed on 53 FFPE kidney sections and quantified (scoring from grade 0 to 3 for C5b-9 deposits in glomeruli and from 0 to 2 in the tubulointerstitial compartment). Clinical data, C3 and sC5b-9 levels at the time of KB were retrospectively collected. Results KB were performed at diagnosis for n = 31. In 22 cases, KB was performed during follow up, under specific treatment (n = 10), without treatment (n = 7), or at disease relapse (n = 5). Twenty-five (47%) were children. Median[Q1-Q3] C3 level at KB was 623 mg/l [236-931]mg/l. Median[Q1-Q3] sC5b-9 level at KB, available in 16, was 374 ng/ml [203-1295]. Median [Q1-Q3] activity and chronicity index were respectively 9[6-12] and 1[0-6]. We confirmed the prognostic impact of chronicity index (p = 0.03) (Figure 1A) without impact of the activity index. Glomerular C5b-9 staining was positive in 47/53 (87%) (grade 1: n = 16 (30%); 2: n = 17 (32%); 3: n = 14 (26%)) and n = 40 (75%) had interstitial C5b-9 staining (grade 1: n = 28 (53%); 2: n = 12 (23%)). Soluble C5b-9 measurement correlated with intensity of C5b-9 glomerular deposit (coef corr = 0.69). As compared to patients with normal C3 level, patients with AP activation had higher proteinuria but kidney function at KB was similar. We found distinct histological features according to C3 plasmatic level (Table 1): patients with low C3 level had higher histological activity index (p = 0.03) and higher glomerular and tubulointerstitial C5b-9 staining (p = 0.001 and p = 0.002 respectively). C5b-9 glomeruli staining allows the identification of 3 groups of KB (1: no or low, 2: medium and 3: high C5b-9 staining) with distinct histological and clinical features. Activity index were higher in groups 2 & 3 (p = 0.05) and chronicity index in groups 1 & 3 (p = 0.003) (Table 2). Renal prognosis was poorer in patients with higher glomerular C5b-9 deposits (Figure 1B). Patients with chronicity index >4 and high C5b-9 staining had the poorest renal survival (Figure 1C). Conclusion Our results suggest that TP activation in glomeruli may have an impact on histological features, contributing therefore to renal prognosis. Deeper exploration of correlation between systemic and in situ complement activation and histological features could allow to better identify patients with worst prognosis or who could benefit from emerging complement inhibition therapeutics.

#5142 THE NATURAL HISTORY OF FSGS IN THE GERMAN CHRONIC KIDNEY DISEASE (GCKD) COHORT

Abstract Background and Aims FSGS is a heterogenic glomerular disease and a common cause of kidney failure in adults. Here we describe the natural history of individuals with FSGS in the German Chronic Kidney Disease (GCKD) cohort. Method From 2010 to 2012, 159 patients with biopsy-proven FSGS have been enrolled into the GCKD study, a prospective observational cohort study (N = 5217). Inclusion criteria were an estimated glomerular filtration rate (eGFR) of 30–60 mL/min/1.73 m2 or overt proteinuria in the presence of an eGFR>60 mL/min/1.73 m2. Baseline date was defined as first study visit. Endpoints were the composite renal endpoint (MAKE); eGFR decline >40%, eGFR< 15ml/min/1.73 m2 or initiation of kidney replacement therapy. The associations between the incidence of MAKE and clinical parameters were analyzed using the Cox proportional hazards regression model. Data relating to baseline demographics, laboratory, comorbidity, and mortality were used. Results The mean age at baseline of patients with FSGS was 52.1 ± 13.6 years. Median proteinuria at baseline was 0.7 g/g (Q1 0.1; Q3 1.8), while mean eGFR was 55.8 ± 23 mL/min/1.73 m². Mean duration of the disease before enrollment was 4.7 ± 6.8 years. The majority (101;63.5%) were male; 69 (43.4%) were diagnosed as primary FSGS using clinical and pathological criteria, 55 (34.6%) as secondary FSGS and for 35 (22%) the etiology was uncertain. At baseline, 37 (23.3%) were under immunosuppressive treatment. Over a follow-up of 6.5 years, 44 reached MAKE, in detail 19 (12%) initiated kidney replacement therapy, an additional 25 (15.8%) experienced a >40% eGFR decline. Albuminuria >0.7 g/g was associated with MAKE, with a HR of 1.47 (95% CI: 1.27-1.7) compared to <0.7 g/g. Higher eGFR at baseline (per 10 ml/min) protected from MAKE with a HR of 0.8 (95% CI: 0.68-0.95). Conclusion The GCKD cohort represents a large study population with lengthy and adjudicated follow-up data. Lower eGFR and higher albuminuria are significant risk factors for progressive kidney disease and ESKD in patients with FSGS.

#4476 PRIMARY GLOMERULAR DISEASES AND LONG-TERM RISKS OF CKD PROGRESSION, CARDIOVASCULAR EVENTS AND DEATH: A SWEDISH NATIONWIDE COHORT STUDY

Abstract Background and Aims Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide (after diabetes and hypertension), little is known about their long-term risks and complications. Method Using data from the Swedish Renal Registry (SRR-CKD) 2005-2021, we compared clinical outcomes between patients with the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD] and membranous nephropathy [MN]) and patients with CKD attributed to non-inflammatory etiologies (i.e. without systemic auto-immune, inflammatory, infectious, hematologic malignancy, genetic disease, or polycystic kidney disease). Poisson models were used to estimate adjusted incidence rate ratios (IRR) of all-cause and cause-specific hospitalizations (cardiovascular-, acute kidney injury-, thromboembolism- and infection-related). Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) of kidney replacement therapy (KRT), major adverse cardiovascular events (MACE) and death. Results We identified 2967 patients with primary glomerular disease (71% men, age 57 years, eGFR 28 mL/min/1.73 m2, uACR 63 mg/mmol) and 40026 patients with a non-inflammatory CKD (64% men, age 74 years, eGFR 22 mL/min/1.73 m2, uACR 20 mg/mmol). As compared to non-inflammatory CKD, patients with primary glomerular diseases were younger, had a lower prevalence of cardiovascular disease, higher eGFR but higher albuminuria. Over median follow-up of 6.3 [3.3;9.9] years, there were median 3.0 [1.0;7.0] hospitalizations per patient, 9890 (23%) KRT, 11708 (27%) MACE, and 21091 (49%) deaths. As compared to non-inflammatory CKD, patients with primary glomerular disease had a lower risk of all-cause (IRR 0.77 [0.75;0.79]), and all cause-specific hospitalizations, MACE (HR 0.56 [0.50;0.63]) and death (HR 0.57 [0.52;0.62], but a similar risk of KRT (HR 1.02 [0.95;1.10]) or AKI (HR 0.84 [0.70;1.02]) (Figure 1). Within primary glomerular diseases and as compared to IgAN, patients with FSGS had a higher risk of death (HR 1.29 [1.03;1.60]) and MACE (HR 1.49 [1.12;1.97]), and patients with MN and MCD had a lower risk of KRT. Conclusion In this nationwide analysis of patients with advanced CKD undergoing nephrologist-care, those with primary glomerular disease have an observed lower risk of adverse clinical events compared to non-inflammatory CKD diseases. However, their risks of AKI or KRT are similar, emphasizing the need of adequate treatment strategies in this population. We speculate that the long-term continuous exposure to comorbidities like diabetes and hypertension in patients with non-inflammatory CKD might explain these differences. Within single primary glomerular disease etiologies, FSGS is associated with the highest risk of cardiovascular and fatal complications. The study received grant support from CSL Vifor.

#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.

Utility of the Kidney Failure Risk Equation and Estimated GFR for Estimating Time to Kidney Failure in Advanced CKD

The Kidney Failure Risk Equation (KFRE) predicts the 2-year risk of kidney failure for patients with chronic kidney disease (CKD). Translating KFRE-predicted risk or estimated glomerular filtration rate (eGFR) into time to kidney failure could inform decision making for patients approaching kidney failure. Retrospective cohort. CKD Outcomes and Practice Patterns Study (CKDOPPS) cohort of patients with an eGFR<60mL/min/1.73m2 from 34 US nephrology practices (2013-2021). 2-year KFRE risk or eGFR. Kidney failure defined as initiation of dialysis or kidney transplantation. Accelerated failure time (Weibull) models used to estimate the median, 25th, and 75th percentile times to kidney failure starting from KFRE values of 20%, 40%, and 50%, and from eGFR values of 20, 15, and 10mL/min/1.73m2. We examined variability in time to kidney failure by age, sex, race, diabetes status, albuminuria, and blood pressure. Overall, 1,641 participants were included (mean age 69±13 years; median eGFR of 28mL/min/1.73m2 [IQR 20-37mL/min/1.73 m2]). Over a median follow-up period of 19 months (IQR, 12-30 months), 268 participants developed kidney failure, and 180 died before reaching kidney failure. The median estimated time to kidney failure was widely variable across patient characteristics from an eGFR of 20mL/min/1.73m2 and was shorter for younger age, male sex, Black (versus non-Black), diabetes (vs no diabetes), higher albuminuria, and higher blood pressure. Estimated times to kidney failure were comparably less variable across these characteristics for KFRE thresholds and eGFR of 15 or 10mL/min/1.73m2. Inability to account for competing risks when estimating time to kidney failure. Among those with eGFR<15mL/min/1.73m2 or KFRE risk>40%), both KFRE risk and eGFR showed similar relationships with time to kidney failure. Our results demonstrate that estimating time to kidney failure in advanced CKD can inform clinical decisions and patient counseling on prognosis, regardless of whether estimates are based on eGFR or the KFRE. Clinicians often talk to patients with advanced chronic kidney disease about the level of kidney function expressed as the estimated glomerular filtration rate (eGFR) and about the risk of developing kidney failure, which can be estimated using the Kidney Failure Risk Equation (KFRE). In a cohort of patients with advanced chronic kidney disease, we examined how eGFR and KFRE risk predictions corresponded to the time patients had until reaching kidney failure. Among those with eGFR<15mL/min/1.73m2 or KFRE risk > 40%), both KFRE risk and eGFR showed similar relationships with time to kidney failure. Estimating time to kidney failure in advanced CKD using either eGFR or KFRE can inform clinical decisions and patient counseling on prognosis.

Relationship between STOX1 gene variations and preeclampsia in Turkish population

Preeclampsia (PE) is a common pregnancy disease that occurs in the second trimester of pregnancy and is characterized by high blood pressure and proteinuria. Recent studies have shown that the STOX1 gene, which is associated with the FOX multigene family and expressed in the early placenta, can directly affect the PE phenotype. STOX1 is a transcription factor that affects the high prevalence of human gestational disease by targeting genes in the pathways that affect cell proliferation and migration. In this study, the effects of STOX1 gene variations Y153H and -922 T > C polymorphisms, previously associated with PE by our team, were evaluated on each other and the disease phenotype. In the study, the results obtained from our previous polymorphism studies were used. As a result of statistical analysis, it was observed that STOX1 Y153H and -922 T > C variations were effective together in the development of early-onset Preeclampsia (EOPE). Our in-silico analysis revealed the deleterious impact of the mutation on the structure and function of the protein. Although PE is a disease that occurs with pregnancy and shows its effects mostly during this period, it has been stated that women and children with a history of PE are more prone to various disorders, especially cardiovascular disease in the following years. Therefore, understanding the pathogenesis of the disease is important for both prevention and treatment process. The variations on STOX1 gene appear to be important in terms of disease risk.

The Prognostic Value of Anti-PLA2R Antibodies Levels in Primary Membranous Nephropathy.

Anti-PLA2R antibodies (Ab) are a diagnostic and prognostic biomarker in primary membranous nephropathy (PMN). We assessed the relationship between the levels of anti-PLA2R Ab at diagnosis and different variables related to disease activity and prognosis in a western population of PMN patients. Forty-one patients with positive anti-PLA2R Ab from three nephrology departments in Israel were enrolled. Clinical and laboratory data were collected at diagnosis and after one year of follow-up, including serum anti-PLA2R Ab levels (ELISA) and glomerular PLA2R deposits on biopsy. Univariable statistical analysis and permutation-based ANOVA and ANCOVA tests were performed. The median [(interquartile range (IQR)) age of the patients was 63 [50-71], with 28 (68%) males. At the time of diagnosis, 38 (93%) of the patients had nephrotic range proteinuria, and 19 (46%) had heavy proteinuria (≥8 gr/24 h). The median [IQR] level of anti-PLA2R at diagnosis was 78 [35-183] RU/mL. Anti-PLA2R levels at diagnosis were correlated with 24 h proteinuria, hypoalbuminemia and remission after one year (p = 0.017, p = 0.003 and p = 0.034, respectively). The correlations for 24 h proteinuria and hypoalbuminemia remained significant after adjustment for immunosuppressive treatment (p = 0.003 and p = 0.034, respectively). Higher levels of anti-PLA2R Ab at diagnosis in patients with active PMN from a western population are associated with higher proteinuria, lower serum albumin and remission one year after the diagnosis. This finding supports the prognostic value of anti-PLA2R Ab levels and their possible use in stratifying PMN patients.

Predictors of treatment outcomes in lupus nephritis with severe acute kidney injury and requirement of dialytic support.

Acute kidney injury (AKI) with the requirement of kidney replacement therapy (KRT) portends a poor prognosis for kidney function in lupus nephritis (LN). This study evaluated the kidney function recovery rates, the rates of reinitiation of KRT, and factors associated with these outcomes in LN. All consecutive patients hospitalized for LN with KRT requirement between 2000 and 2020 were included. Their clinical and histopathologic characteristics were retrospectively registered. The outcomes and associated factors were evaluated by multivariable Cox regression analysis. Among 140 patients, 75 (54%) recovered kidney function, with recovery rates of 50.9% and 54.2% by 6 and 12months of therapy. The factors associated with a lower probability of recovery included a previous history of LN flares, worse eGFR and higher proteinuria at presentation, immunosuppression with azathioprine, and hospitalizations within 6months of therapy initiation. There was no difference in the kidney function recovery rates between mycophenolate and cyclophosphamide treatment schemes. Out of 75 patients who recovered kidney function, 37 (49%) reinitiated KRT, with KRT reinitiation rates of 27.2% and 46.5% by 3 and 5years. Seventy-three (52%) patients had at least one hospitalization within 6months of initial therapy, 52 (72%) of them secondary to infectious events. Approximately 50% of patients with LN and KRT requirement recover kidney function within 6months. The risk-to-benefit ratio decisions may be aided by clinical and histological factors. These patients require close follow-up as ≈50% of those who recover kidney function will reinitiate dialysis in the long term. Key Points • Approximately 50% of patients with severe acute lupus nephritis with the need for kidney replacement therapy requirement recover their kidney function. • The factors associated with a lower probability of recovery of kidney function include a previous history of LN flares, worse eGFR and higher proteinuria at presentation, immunosuppression with azathioprine, and hospitalizations within 6 months of therapy initiation. • Patients who recover kidney function will require close follow-up as around 50% of them will eventually reinitiate kidney replacement therapy.

Multimorbidity in nephrotic syndrome.

Nephrotic syndrome (NS) is characterized by high proteinuria (over 3,5g/24 hrs), hypalbuminaemia, general edemas and hypercoagulation. Beside of primary glomerulonephritides this is found in secundary glomerulopaties eg. diabetes, systemic inflammatory diseases, oncology, damage by drugs and poisoning, by alergy, serious infections and in children from hereditary reasons. The most frequent reason for NS in adults patiens is diabetes and diabetes with nephropathy represents almost 40% of dialysed patiens. From this point of view, there is great interest focusing on gliflozins (SGLT2 inhibitors) with positive nephroprotecive effect. It leads do increasing of glycosuria with concomitant natriuresis and osmotic diuresis. The effect is proportional to glomerulal filtration, but the effect on natriuresis stay in all stages of renal insufficiency.

Relation of early-stage renal insufficiency and cardiac structure and function in a large population of asymptomatic Asians: a cross-sectional cohort analysis.

Few studies have addressed early-stage kidney disease and preclinical cardiac structural and functional abnormalities from a large-scale Asian population. Further, the extent to which measures of myocardial function and whether these associations may vary by testing various formulas of renal insufficiency remains largely unexplored. To explore the associations among renal function, proteinuria, and left ventricular (LV) structural and diastolic functional alterations. A cross-sectional, retrospective cohort study. Registered data from a cardiovascular health screening program at MacKay Memorial Hospital from June 2009 to December 2012. Asymptomatic individuals. Renal function was evaluated in terms of estimated glomerular filtration rate (eGFR) by both MDRD and CKD-EPI formulas and severity of proteinuria, which were further related to cardiac structure, diastolic function (including LV e' by tissue Doppler), and circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) level. Among 4942 participants (65.8% men, mean age 49.4 ± 11.2 years), the mean CKD-EPI/MDRD eGFR was 90.6 ± 15.7 and 88.5 ± 16.9 ml/min/1.73m2, respectively. Lower eGFR, estimated either by the MDRD or CKD-EPI method, and higher proteinuria were significantly associated with lower LV e' and higher NT-proBNP (all p<0.05) even after adjusting for clinical covariates. In general, lower eGFR estimated by CKD-EPI and MDRD displayed similar impacts on worsening e' and NT-proBNP, rather than E/e', in multivariate models. Finally, lower LV e' or higher composite diastolic score, rather than E/e', demonstrated remarkable interaction with eGFR level estimated by either CKD-EPI or MDRD on circulating NT-proBNP level (p interaction <0.05). Proteinuria was estimated using a urine dipstick rather than more accurately by the urine protein-to-creatinine ratio. Also, pertaining drug history and clinical hard outcomes were lacking. Both clinical estimate of renal insufficiency by eGFR or proteinuria, even in a relatively early clinical stage, were tightly linked to impaired cardiac diastolic relaxation and circulating NT-proBNP level. Elevation of NT-proBNP with worsening renal function may be influenced by impaired myocardial relaxation.

Study of the erythrocyte sedimentation rate in diabeticpatients

The morbidity and mortality of diabetus mellitus - related complications can be greatly reduced by constantly checking patients blood sugar ( self - monitoring or HbAlc testing). Some patients can not receive this comprehensive diabetic care. This study try to ciarify the relation between some inflammatory markers and sugar control in diabetic patients. The study includes 50 patients ( 18 males and.32 females ) from samarra city . All were reviewed with history, thorough examination, and investigations. Out of 50 patients with diabetes, 39 had high blood sugar, 40 had high ESR, 9 had increase in both blood sugar and ESR, 17 had abnormal (high) blood sugar and albuminuria, 17 had high ESR and albuminuria. Other causes of high ESR should be excluded such as rheumatoid arthritis, anemia, haematological diseases and infection like brucellosis .

High exposure to tacrolimus is associated with spontaneous remission of recurrent membranous nephropathy after kidney transplantation.

We aimed to characterize the incidence and clinical presentation of membranous nephropathy (MN) after kidney transplantation (KT), and to assess allograft outcomes according to proteinuria rates and immunosuppression management. Multicenter retrospective cohort study including patients from six Spanish centers who received a KT between 1991-2019. Demographic, clinical, and histological data were collected from recipients with biopsy-proven MN as primary kidney disease (n=71) or MN diagnosed de novo after KT (n=4). Up to 25.4% of patients with biopsy-proven MN as primary kidney disease recurred after a median time of 18.1 months posttransplant, without a clear impact on graft survival. Proteinuria at 3-months post-KT was a predictor for MN recurrence (rMN, HR 4.28; P=0.008). Patients who lost their grafts had higher proteinuria during follow-up [1.0 (0.5-2.5) vs 0.3 (0.1-0.5) g/24h], but only eGFR after recurrence treatment predicted poorer graft survival (eGFR<30ml/min: RR=6.8). We did not observe an association between maintenance immunosuppression and recurrence diagnosis. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence (trough concentration/dose ratio: 2.86vs 1.18; P=0.028). Up to 94.4% of KT recipients received one or several treatments after recurrence onset: 22.2% rituximab, 38.9% increased corticosteroid dose, and 66.7% ACEi/ARBs. Only 21 patients had proper antiPLA2R immunological monitoring. One-fourth of patients with biopsy-proven MN as primary kidney disease recurred after KT, without a clear impact on graft survival. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence.

Clinical and histopathologic predictors of recurrent glomerulonephritis after kidney transplantation.

We evaluated the long-term outcomes of recurrent glomerulonephritis (RGN) using clinical, histopathological, and demographic predictors. A retrospective cohort study of kidney transplant recipients (KTR) in two renal centers between 2005 and 2020.Clinical and native kidney histological data were analyzed. The risk factors and outcomes of each primary glomerulonephritis subtype were assessed using Cox methods. 336 recipients with primary glomerulonephritis were analyzed. RGN was diagnosed in 17%, 20%, 25%, and 13% of recipients with IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and membranoproliferative glomerulonephritis (MPGN), respectively. Median time to recurrence was shortest in FSGS (.6 years IQR .2-2.9) and longest in MN (6.3 years IQR 3.3-8.0) whereas time to graft loss after diagnosis was shortest in MPGN (.3 years IQR .1-1.7) and longest in IgAN (2.9year IQR 1.3-4.3). Recipients with recurrent IgAN were likely to be younger, have higher proteinuria at diagnosis, receive living donor allografts, receive cyclosporine treatment, have a history of acute rejection, and have segmental sclerosis in native glomeruli. Younger age of the donors, higher proteinuria at diagnosis, alemtuzumab, proteinuria within the first 12 months, acute rejection, low baseline eGFR, mesangial proliferation, and IgG and IgA deposits were associated with FSGS recurrence. MPGN recurrence was predicted by lower BMI at transplantation, and crescentic native disease. Death-censored graft survival at 5-, 10-, and 15-years was 83%, 51%, and 29% in the RGN group and 95%, 93%, and 84%, respectively in the non-RGN group. Over 15 years, recipients with RGN are nine times more likely than those without RGN to lose their grafts, regardless of donor type, acute rejection, and baseline eGFR. Transplant recipients of related donor allograft were not more likely to have recurrent GN than non-related donors.

Impact of lenvatinib-induced proteinuria and renal dysfunction in patients with thyroid cancer.

Proteinuria is the most frequent adverse event of lenvatinib use. However, the association between lenvatinib-induced proteinuria and renal dysfunction remains unclear. We retrospectively reviewed medical records of patients with thyroid cancer without proteinuria treated with lenvatinib as a first-line systemic therapy at the initiation of treatment to assess the association between lenvatinib-induced proteinuria and renal function and the risk factors for the development of ≥3+ proteinuria on a dipstick test. Proteinuria was assessed by the dipstick test throughout the treatment in all cases. Of the 76 patients, 39 developed ≤2+ proteinuria (low proteinuria group) and 37 developed ≥3+ proteinuria (high proteinuria group). There was no significant difference in estimated glomerular filtration rate (eGFR) between high and low proteinuria groups at each time point, but there was a trend toward a significant decrease in eGFR of -9.3 ml/min/1.73 m2 in all patients after 2 years of treatment. The percentage of change in eGFR (ΔeGFR) significantly decreased in the high proteinuria group compared to that in the low proteinuria group (ΔeGFR: -6.8% vs. -17.2%, p=0.04). However, there was no significant difference in development of severe renal dysfunction with eGFR <30 ml/min/1.73 m2 between the two groups. Moreover, no patients permanently discontinued treatment because of renal dysfunction in both groups. Furthermore, renal function after completion of lenvatinib was reversible. There was no association between the degree of lenvatinib-induced proteinuria and renal function. Therefore, treatment should be continued with attention to renal function, regardless of the degree of proteinuria.

Alterations in the Circulating Proteome Associated with Albuminuria.

We describe circulating proteins associated with albuminuria in a population of African American Study of Kidney Disease and Hypertension with CKD (AASK) using the largest proteomic platform to date: nearly 7000 circulating proteins, representing approximately 2000 new targets. Findings were replicated in a subset of a general population cohort with kidney disease (ARIC) and a population with CKD Chronic Renal Insufficiency Cohort (CRIC). In cross-sectional analysis, 104 proteins were significantly associated with albuminuria in the Black group, of which 67 of 77 available proteins were replicated in ARIC and 68 of 71 available proteins in CRIC. LMAN2, TNFSFR1B, and members of the ephrin superfamily had the strongest associations. Pathway analysis also demonstrated enrichment of ephrin family proteins. Proteomic techniques have facilitated understanding of pathways that mediate decline in GFR. Albuminuria is a key component of CKD diagnosis, staging, and prognosis but has been less studied than GFR. We sought to investigate circulating proteins associated with higher albuminuria. We evaluated the cross-sectional associations of the blood proteome with albuminuria and longitudinally with doubling of albuminuria in the African American Study of Kidney Disease and Hypertension (AASK; 38% female; mean GFR 46; median urine protein-to-creatinine ratio 81 mg/g; n =703) and replicated in two external cohorts: a subset of the Atherosclerosis Risk in Communities (ARIC) study with CKD and the Chronic Renal Insufficiency Cohort (CRIC). In cross-sectional analysis, 104 proteins were significantly associated with albuminuria in AASK, of which 67 of 77 available proteins were replicated in ARIC and 68 of 71 available proteins in CRIC. Proteins with the strongest associations included LMAN2, TNFSFR1B, and members of the ephrin superfamily. Pathway analysis also demonstrated enrichment of ephrin family proteins. Five proteins were significantly associated with worsening albuminuria in AASK, including LMAN2 and EFNA4, which were replicated in ARIC and CRIC. Among individuals with CKD, large-scale proteomic analysis identified known and novel proteins associated with albuminuria and suggested a role for ephrin signaling in albuminuria progression.

Urine proteome profile in primary podocytopathies

BACKGROUND. Primary focal segmental glomerulosclerosis (FSGS) and membranous nephropathy (MN) are diseases with primary podocyte damage with high proteinuria and nephrotic syndrome. While the mechanisms in primary MN are well understood, the pathogenesis of primary FSGS is still unknown, and therefore, the search for biomarkers that could expand ourunderstanding of its pathogenetic mechanisms. THE AIM: to determine the urine proteomic profile of patients with primary podocytopathies – FSGS in comparison with MN. PATIENTS AND METHODS. The study included 48 patients with a morphologically confirmed diagnosis of CGN occurring with nephrotic syndrome – 32 men and 16 women. In 18 patients, a decrease in glomerular filtration rate &lt; 60 ml/min/1.73 m2 was observed. The histological diagnosis was confirmed by biopsy: 31 patients had FSGS, 17 patients with MN were included as a comparison group. The study of the urinary proteome was carried out by high performance liquid chromatography/mass spectrometry. RESULTS. In patients with FSGS, compared with the MN group, an increased content of 22 different proteins was noted, the most abundant were apolipoprotein A-I, hemopexin, vitronectin, pigment epithelial growth factor, components of the complement system (C3, C4b, factors B and H), retinol – and vitamin D-binding proteins, alpha-2-HS-glycoprotein, histidine-rich glycoprotein, plasma C1 protease inhibitor. In MN, increased urinary excretion of the complement component C2, fibrinogen alpha chain, osteopontin, and the SH3 domain-binding glutamic acid-rich-like protein 3, was detected. CONCLUSION. The proteomic profile of urine in FSGS, compared to MN, reflects the activation of variety of pathological processes – podocyte damage, involvement of parietal epithelial cells, tubulo-interstitial damage, accumulation of extracellular matrix, and complement activation process.

Living Donor Liver Transplantation Alone Is Not Inferior to Combined Kidney Liver Transplant for Cirrhotic Patients With Chronic Kidney Disease

Chronic kidney disease (CKD) is common in patients with chronic liver disease (CLD) as is acute kidney injury (AKI). The differentiation between CKD vs AKI is often difficult and sometimes the both may coexist. A combined kidney-liver transplant (CKLT) may result in a kidney transplant in patients whose renal function is likely to recover or at least who have stable renal function post-transplant. We retrospectively enrolled 2742 patients who underwent living donor liver transplant at our center from 2007 to 2019. This audit was carried out in liver transplant recipients with CKD 3 to 5 who underwent either liver transplant alone (LTA) or CKLT to look at outcomes and long-term evolution of renal function. Forty-seven patients met the medical eligibility criteria for CKLT. Of the 47 patients, 25 underwent LTA and the rest 22 underwent CKLT. The diagnosis of CKD was made according to the Kidney Disease: Improving Global Outcomes classification. Preoperative renal function parameters were comparable between the 2 groups. However, CKLT patients had significantly lower glomerular filtration rates (P=.007) and higher proteinuria (P=.01). Postoperatively, renal function, and comorbidities were comparable between the 2 groups. Survival was similar at 1, 3, and 12 months, respectively (log-rank; P=.84,=.81, and=.96, respectively). At the end of the study period, 57% of patients who survived in LTA groups had stabilized renal function (Creatinine=1.8 ± 0.6 mg/dL). Liver transplant alone is not inferior to CKLT in living donor situations. Renal dysfunction is stabilized in the long term whereas long-term dialysis may be carried out in others. Living donor liver transplantation alone is not inferior to CKLT for cirrhotic patients with CKD.

Investigating the relationship between right ventricular size and function with pre-eclampsia: A two-group cross-sectional study.

Pre-eclampsia is a multisystem disorder characterized by symptoms of high blood pressure and proteinuria during pregnancy. It is associated with many complications and maternal and fetal mortality. This disorder may be associated with many cardiovascular complications and affect the function of the heart. Therefore, in this study, the structure and function of the right ventricle (RV) in patients with pre-eclampsia have been investigated using echocardiography. This cross-sectional study was conducted in Ghaem Hospital of Mashhad. Thirty-twopregnant women, whose gestational age was 20 weeks or more, were considered as the case group after evaluating blood pressure and confirming proteinuria and pre-eclampsia. Thirty-twohealthy pregnant women were also included in the study as a control group. The function of the RV was evaluated using two-dimensional transthoracic echocardiography. Investigating the results of the study shows that in pregnant women with pre-eclampsia, RV fractional area change, and RV strain indices have decreased significantly compared with healthy pregnant women (p < 0.05). Also, the statistical analysis shows that no significant differences were observed in the two groups in terms of echocardiographic indices E, A, É, E/É, É/Á, E/A, pulmonary artery pressure, Tricuspid Annular Plane Systolic Excursion, right ventricular diameter, and left ventricle mass index. According to the results of the study, it can be generally said that pre-eclampsia may be associated with changes in the function and echocardiographic indices of the RV and may result in cardiac complications.

Design and Baseline Data of the Diabetes Registration Study: Guangzhou Diabetic Eye Study

Purpose The incidence and risk factors for diabetic retinopathy (DR) in southern China remain unclear. This project aims to explore the onset and progression of DR and their determinants through a prospective cohort in South China. Methods The Guangzhou Diabetic Eye Study (GDES) recruited patients with type 2 diabetic registered in the community health centers in Guangzhou, China. Comprehensive examinations were performed including visual acuity, refraction, ocular biometry, fundus imaging, blood and urine tests. Results A total of 2305 eligible patients were included in the final analysis. In total, 14.58% of the participants had any DR and 4.25% had vision-threatening DR (VTDR), among which 76 (3.30%), 197 (8.55%), 45 (1.95%) and 17 (0.74%) were classified as mild NPDR, moderate NPDR, severe NPDR and PDR, respectively. There were 93 (4.03%) patients with diabetic macular edema (DME). The presence of any DR was independently associated with a longer duration of DM, higher degree of HbA1c, insulin treatment, higher average arterial pressure, higher concentration of serum creatinine, presence of urinary microalbumin, older age, and lower body mass index (BMI) (all p < 0.001). For VTDR, seven factors were significant: older age, a longer duration of DM, higher concentration of HbA1c, use of insulin, lower BMI, higher concentration of serum creatinine, and high albuminuria (all p < 0.05). These factors were also independently associated with DME (all p < 0.001). Conclusion The GDES is the first large-scale prospective cohort study of the diabetic population in southern China, which will help to identify novel imaging and genetic biomarkers for DR in this population.