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BACKGROUND AND AIMS The gold standard for measurement of protein excretion is a 24-h urine collection. However, due to the cumbersome nature as well as the frequent errors in sample collection, it has been suggested that the measurement of albumin-creatinine ratio (ACR) in a spot urine sample could replace 24-h proteinuria as a valid method for the diagnosis and follow-up of renal disease, which is supported by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The aim of our study was to assess the correlation between 24-h proteinuria and spot urine ACR in patients with biopsy-proven glomerulonephritis, METHOD We identified patients with biopsy-proven glomerular diseases who were evaluated during their disease course at our center between 1 January 2005 and 31 December 2021, and included patients with paired 24 h and spot urine samples simultaneously collected at the same day. We excluded patients with interstitial or vascular causes for kidney disease. We contrasted correlation of ACR and 24 h proteinuria according to demographic data, glomerular filtration rate measured at the day of urine collection, and type of glomerular disease. RESULTS A total of 977 paired 24-hr proteinuria and spot urine ACR samples were collected at the same day from 370 patients and included in this study. The mean age of the selected population was 52.1 ± 17.7 years, with a median serum creatinine of 1.26 mg/dL (IQR: 0.94–1.74) and mean eGFR measured by CKD-EPI of 62.4 ± 30.1 mL/min. Median 24-h proteinuria was 1.48 g/day (IQR: 0.59–3.39), and the median ACR was 539 mg/g (IQR: 131–1569). We found an excellent correlation between ACR and 24-h proteinuria (Spearman's r = 0.86, P 3 g/day (Spearman's r = 0.50, P ROC analysis showed that a ACR cutoff of >250 mg/g was the best predictor for 24-h proteinuria >1 g/day, with an area under the curve (AUC) of 0.933, sensitivity 91% and specificity 81%, while an ACR cutoff of >800 mg/g best predicted a 24-hour proteinuria of >3.5 g/day, with an AUC of 0.922, sensitivity of 92% and specificity of 76%. CONCLUSION There is an excellent correlation between ACR and 24-h proteinuria in patients with proteinuria 3 g/day, ACR correlates poorly with proteinuria. We suggest that patients with higher grade proteinuria should always be assessed with a 24-h urine sample protein excretion for therapeutic decisions and follow-up in glomerular diseases.

BACKGROUND AND AIMS The complement system was not initially thought to be associated with the development of ANCA-associated vasculitis (AAV). Convincing evidence from animal models and clinical observations indicates, however, that activation of the complement system, the alternative pathway (ACP) in particular, is pivotal for the development of AAV. Recently, a phase 3 clinical trial has shown that C5a receptor inhibition with avacopan was effective in replacing high dose glucocorticoids in AAV patients treated with rituximab or cyclophosphamide during induction treatment. We hypothesized that in AAV, a disorder in regulatory factors of ACP or in its related proteins (FHR-1, FHR-2, FHR-5) could be present, similar to other diseases in which its dysregulation have been shown. Method We measured longitudinal levels of alternative complements factors (FH, FB, properdin, FHR-1, FHR-2, FHR-5) and performed a genetic study for these factors in three cohorts: active renal ANCA vasculitis (active AAV, n = 54), inactive ANCA vasculitis (remission, n = 48) and in a control cohort of healthy individuals (n = 99). RESULTS ANCA serology was positive in all patients; 83.3% showed activity against MPO, whereas activity against PR3 was identified in 16.7% of patients. Median BVAS at the onset was 15 (IQR 14–19). Extrarenal involvement was present in 46.3% of participants. Haplotype CFH-H6 and the allele CFB32R are significantly associated with increased risk to develop AAV [OR 3.32; 95% confidence interval (95% CI) 1.39–7.89; P = 0.008 and OR 1.71, 95% CI 1.11–2.54; P = 0.008, respectively]. The allele frequency of ΔCFHR3/1 was significantly decreased in patients with severe AAV (T3, BVAS > 16) compared with patients with a lower BVAS score (T1-T2 ≤ 15). Circulating levels of regulatory factors (FH, FB, properdin) were significantly lower in patients with active disease compared to samples in remission, and FHR1 (FH competitor) levels were higher. C3 levels increased over time, while sC5b-9 decreased after initiating the immunosuppressive treatment, with the biggest change observed after the first month of treatment. After 12 months of follow-up, FHR-1 levels decreased in responder patients and did not decrease in nonresponders. CONCLUSION This is the first study to associate the presence of certain alleles of regulatory factors of the alternative complement pathway (Factor H and Factor B) with an increased risk of developing ANCA-associated vasculitis. Likewise, the absence of the ΔCHR3-CFHR1 deletion was associated with more severe forms of the disease. We could conclude that ACP is not a simple additional factor in the inflammatory loop in AAV and, like in other glomerular diseases related to ACP, dysregulation of FH and its regulatory proteins play an essential role in its development.

BACKGROUND AND AIMS Acute interstitial nephritis (AIN) is one of the most frequent causes of acute kidney injury (AKI). Interstitial inflammation can lead to tubular epithelial infiltration producing tubular dysfunction, which could be clinically detected by glycosuria (with or without Fanconi syndrome), leukocyturia, microscopic haematuria or tubular proteinuria. The aim of this study was to determine the predictive value of renal glycosuria in AKI for the diagnosis of AIN. METHOD We conducted a retrospective study of kidney biopsies performed at out centre between May 1998 and December 2021, and included patients whose kidney biopsy was performed while presenting with AKI. We excluded patients with other indications for kidney biopsy, patients with diabetes mellitus and patients who presented a serum glucose level of > 120 mg/dL at presentation. We registered demographic, clinical and laboratory variables at presentation of AKI, and compared patients with a final diagnosis of AIN to patients with other causes of AKI. RESULTS The study included 211 patients; 39 patients (18.5%) with a diagnosis of AIN and 172 patients (81.5%) with other diagnoses for AKI. Eight patients with AIN presented with renal glycosuria (20.5%) compared with seven patients with other causes of AKI (4.1%) (P 100 mg/dL of glycosuria had a specificity of 99.4% for the diagnosis of AIN, with a positive predictive value of 75% (24.3–96.6) and a positive likelihood ratio of 13.2 (1.4–123.8). CONCLUSION AIN can lead to proximal tubular dysfunction, which can be clinically expressed as renal glycosuria. The presence of renal glycosuria in patients with AKI guides towards the diagnosis of AIN, with an excellent specificity when glycosuria > 100 mg/dL.

BACKGROUND AND AIMS It has been postulated that the protein-creatinine ratio in spot urine sample (uPCR) could be an adequate alternative to measurement of proteinuria in 24-h urine samples (24-h proteinuria), which despite being the gold standard for the diagnosis and follow-up of patients with kidney disease, its accuracy is frequently influenced by incorrect sample collection. Several studies have shown a correlation between uPCR in spot urine samples and 24-h proteinuria. However, in daily clinical practice we often find significant differences between both measurements. Therefore, we set out to conduct this study to analyze the concordance between uPCR in first morning spot urine samples and 24-h proteinuria in patients with biopsy-proven glomerular diseases. METHOD We identified patients with biopsy-proven glomerular diseases who were evaluated during their disease course at our center between January 1, 2005 and December 31, 2021, and included patients with paired 24-h protein excretion measurement and spot urine samples that measured protein and creatinine concentration, simultaneously collected at the same day. We excluded patients with interstitial or vascular causes for kidney disease. We performed correlation analyses of uPCR and 24-h proteinuria globally and analyzed the influence of demographic data as well as eGFR and type of glomerular disease in this relationship. The concordance between both measurements was compared using intra-class correlation coefficients (ICC) and Bland–Altman plots. RESULTS About 351 patients with simultaneous uPCR and 24-h proteinuria measured at the same day were included in the study, 67.2% were male and the mean age was 53.9 ± 17.9. Median serum creatinine was 1.28 mg/dl (IQR 0.95–1.86) and mean eGFR measured by CKD-EPI was 60.1 ± 30.6 mL/mi/1.73 m2. Median 24-h proteinuria was 1.70 g/day (IQR: 0.62–3.45) and median uPCR was 1.09 g/g (IQR: 0.35–2.70). Wilcoxon rank test showed a systematic underestimation of uPCR compared with 24-h proteinuria (Z = −8.22, P 60 mL/min of 0.79 (CI 95%: 0.71–0.85, P 3 g/day for 24-h proteinuria, and 3 g/g for uPCR), we performed Cohen's κ test to determine agreement, finding moderate agreement between measurements (κ = 0.46, P CONCLUSION The level of concordance between proteinuria from 24-h urine samples and protein–creatinine ratio from spot urine samples is high regardless of eGFR, age, sex and type of glomerular disease. However, the level of agreement decreases in nephrotic-range proteinuria. Therefore, we suggest that uPCR could be an appropriate measure to assess and follow-up patients with glomerular diseases and non-nephrotic range proteinuria, while the degree of proteinuria should still be monitored with 24-h urine specimens in patients with proteinuria >3.5 g/day.

BACKGROUND AND AIMS An elevated proportion of haemodialysis patients require at some point the utilization of a tunnelled central venous catheter (tCVC) as vascular access. There are several designs for tCVC that differ in the type of material used, the number of lumens, length and tip design. Currently, a scarcity of studies has compared the different types of tCVC. The aim of this study was to analyse whether there were differences in catheter survival between three types of tCVC: symmetrical-tip, step-tip and split-tip catheters. METHOD We conducted a prospective observational study that included all incident patients in two haemodialysis centres between 2016 and 2020, with a minimum follow-up of 6 months (until June 2021). The election of tCVC type was performed by the interventional radiologist in a random manner according to available tCVC. We collected demographic data (age, sex, dialysis site), comorbidities (diabetes mellitus, Charlson Index), laboratory values (albumin, haemoglobin, C-reactive protein), dialysis adequacy (KtV, dose of urokinase used for maintaining tCVC patency) and a number of tCVC used. RESULTS Table 1 shows the characteristics of the 182 tCVC included in this study, stratified in three groups according to the type of tip, without observing significant differences. We did not find significant differences in catheter survival between the three types of tCVC, neither globally nor after adjusting for other confounding variables. However, catheter survival decreased after the second tCVC independent of the type of tCVC (cumulative incidence: tCVC 1 versus >1: 180 days 7% versus 32%; 360 days 10% versus 34%; 720 days 11% versus 34%, P = 0.001) Catheter survival also decreased in patients >70 years old (cumulative incidence 70 years: 360 days 7.6% versus 20%; 720 days 10.8% versus 21.1%, P = 0.035) CONCLUSION There are no differences in catheter survival between the three types of tCVC. The patency of vascular access decreases with age and the number of previously used catheters, being both independent risk factors for catheter dysfunction.

BACKGROUND AND AIMS COVID-19 is associated with an increased mortality in maintenance haemodialysis patients. Considering the baseline immunosuppressed status of this population, humoral immune responses to SARS-CoV-2 vaccination remain to be studied. There is no information regarding sustained immune response in this population after a third booster dose following complete m-RNA vaccination. The aim of our study was to describe the humoral immune response in haemodialysis patients following a complete SARS-CoV-2 vaccine schedule and a third booster dose, and explore the factors associated with a sustained immune response. METHOD We conducted a retrospective study in which we included haemodialysis patients with or without (naïve) previous COVID-19 infection. Patients received the following vaccination schedule: two initial doses of m-RNA vaccine with a 4-week interval (complete immunization) followed by a third booster dose at least 4 months after the second initial dose. IgG anti-SARS-CoV-2 spike antibody titles were measured before the first initial vaccine dose and then monthly up to 3 months after the booster dose. We excluded patients without baseline serological samples and those who did not receive the full vaccination schedule. RESULTS The study included 182 haemodialysis patients with a mean age of 68.5 ± 14.5 years, 63.2% were males and 14.3% were under immunosuppression, 67.7% were responders to HBV vaccine and 18.1% had been infected with SARS-CoV-2 prior to vaccination. After the first two vaccine doses, 96.5% developed immediate humoral immune response, and 91.5% remained with positive anti-SARS-CoV-2 spike antibodies after 4 months from complete vaccination. Median antiSARS-CoV-2 spike antibody titles were significantly higher in patients with previous COVID-19 infection and HBV vaccine responders, both immediately (40 000 AU/mL versus 2926 AU/mL, P In the 4 months between complete initial vaccination and the third booster dose, the mean monthly decrease in antiSARS-CoV-2 spike antibody titles was of 31.8% (±18.9) and was significantly lower in patients with prior COVID-19 infection compared with naïve patients (17.2% versus 34.8%, P After the third booster dose, 98.2% of patients showed positive anti-SARS-CoV-2 S antibodies, and this proportion remained stable in the following 3 months. Nevertheless, median anti-SARS-CoV-2 spike antibody titles remained higher in patients with prior COVID-19 both immediately and after 3 months. However, we observed a more sustained humoral response after the booster dose, with a lower mean monthly decrease in antibody titles compared with the initial vaccine schedule (31.8% to 22.6%, P Multivariate logistic regression for the risk of a >25% monthly decrease in antibodies showed that prior infection with COVID-19 was a protective factor both after the complete initial vaccination {OR: 0.23, [95% confidence interval (95% CI) 0.06–0.87]} as well as after the third dose (OR: 0.23, 95% CI 0.06–0.81). CONCLUSION Vaccination with m-RNA anti-SARS-CoV-2 is effective in eliciting an immediate humoral response in haemodialysis patients, with a progressive reduction in immune response after 4 months particularly in COVID-19 naive patients. A third booster dose enhances the immune response with significantly higher antibody levels and more sustained humoral immune after 3 months in haemodialysis patients.

Background and Aims Kidney fibrosis has been reported to be a key progression hallmark of chronic kidney disease (CKD). It seems likely that a precise biomarker of renal fibrosis extension would contribute to predict accurately the risk of a decline in glomerular filtration rate (eGFR). Previous studies have shown that the assessment of urinary Dickkopf-3 (uDKK3), a stress induced tubular epithelial-derived profibrotic glycoprotein, might be a potential tubulointerstitial fibrosis biomarker and might identify patients at short-term risk of eGFR loss. We aim to evaluate uDKK3 as a potential biomarker for long-term CKD progression in a cohort with various etiologies of CKD, and subsequently in an overt diabetic nephropathy cohort. We also tested the role of treatment with RAAS blockers on the uDKK3 levels and if the treatment could modify them. Method We prospectively studied two independent cohorts consisted of 356 patients with stage 2-3 CKD. Progreser cohort comprised 255 patients with heterogeneous etiologies of CKD and Pronedi cohort 101 patients with overt diabetic nephropathy. The primary outcome was the time to the first event of the composite endpoint (>50% increase in serum creatinine concentration, end-stage kidney disease [ESKD], or death). We divided patients into tertiles according to their baseline uDKK3 levels: less than 1092 pg/mg (Tertile 1, T1), between 1092-5050 pg/mg (Tertile 2, T2) and higher than 5050 pg/mg (Tertile 3, T3). We used the cut point of T3 as an exploratory cut-off. Cox regression models were used to adjust for potential effects of confounders or modifiers: age, gender, mean arterial pressure, body mass index (BMI), urine albumin/creatinine ratio, urine protein/creatinine ratio and serum creatinine. Mixed-effects models were adjusted to study longitudinal data. Results Progreser cohort and Pronedi cohort did not differ in their clinical baseline characteristics except in proteinuria. At baseline, uDKK3 levels were not different between different etiologies or both cohorts, median uDKK3 was 2199 (IQR: 658-7618) pg/mg in the Progreser cohort and 3041 (IQR: 653-9777) pg/mg in the Pronedi cohort (p:0.56). Median time of follow-up was 36 months. Forty-nine patients (19 %) in Progreser cohort and 31 patients (31%) in Pronedi cohort reached the primary composite outcome. Baseline uDKK3 was significantly higher in patients who reached primary outcome. In Cox multivariate model, after adjustment for potential confounders, the highest levels of uDKK3 were found to be an independent factor for renal progression in Progreser cohort (HR 1.83, CI95% 1.11-3.31) and in Pronedi cohort (HR 2.74, CI95% 1.09-6.98). Both in the Progreser and the Pronedi cohorts, uDKK3 levels above 5050 pg/mg, were associated with a lower eGFR, higher proteinuria and were independently associated with a worse renal survival. uDKK3 gradually increased in the following months, especially in patients with higher proteinuria. Treatment with RAAS-blockers did not modify uDKK3 after 4 or 12 months of treatment. Conclusion In this study, uDKK3 ratio identified patients at high risk for long-term kidney disease progression regardless of the etiology of CKD. The hypothesis was generated in a cohort of patients with CKD of heterogeneous etiologies and was further confirmed in a cohort with overt diabetic nephropathy. The predictive role of uDKK3 persisted after adjusting by eGFR and proteinuria. uDKK3 is the first non-invasive biomarker of renal fibrosis and might serve as a useful biomarker for kidney disease progression. Therefore uDKK3 could be used by clinicians to optimize staging for renal progression and monitor therapeutic efficacy of different measures to halt CKD progression.

Background and Aims There is an increased risk of thrombotic complications in patients with COVID-19. Hemodialysis patients are already at an increased risk for thromboembolic events such as stroke and pulmonary embolism. The aim of our study was to determine the incidence of late thrombotic complications (deep vein thrombosis, pulmonary embolism, stroke, new-onset vascular access thrombosis) in maintenance hemodialysis patients after recovery from COVID-19. Method We performed a retrospective cohort study of 200 prevalent hemodialysis patients in our center at the start of the pandemic. We excluded incident patients after the cohort entry date and those who required hemodialysis for acute kidney injury, and excluded patients with less than 1 month follow-up due to kidney transplantation or death from non-thrombotic causes. Results 185 prevalent hemodialysis patients finally met the inclusion criteria; 37 patients (17.6%) had SARS-CoV-2 infection, out of which 10 (27%) died during the acute phase of disease without evidence of thrombotic events. There was an increased risk of thrombotic events in COVID-19 survivors compared to the non-infected cohort (18.5% vs 1.9%, p=0.002) after a median follow-up of 7 months. Stroke incidence was 38.9 episodes/1000 patient-years in patients infected with SARS-CoV-2, compared to an incidence of 2.8 episodes/1000 patient-years in non-infected patients during the follow-up period. The median time from diagnosis of SARS-CoV-2 to the first thrombotic event was 62 days (interquartile range 5-118 days). Survival analysis with Kaplan-Meier curves revealed an increase in the rate of thrombotic events after SARS-CoV-2 compared to non-infected patients (see Figure 1). Mean survival from thrombotic event was 6.1±0.4 months in the COVID-infected group, compared to 6.97±0.04 months in the non-infected group (p Conclusion There is an increased risk of late thrombotic complications in hemodialysis patients after infection with COVID-19. Further studies should evaluate the benefit of prolonged prophylactic anticoagulation in hemodialysis patients after recovery from COVID-19.

Background and Aims Inflammation is a main mechanism for the pathogenesis and progression of diabetic kidney disease (DKD). Interleukin-6 (IL-6) is an important inflammatory mediator and different studies have suggested its involvement in the pathogenesis of DKD. The aim of our study was to evaluate the association between IL-6 levels and progression of DKD in patients with type 2 diabetes. We also tested whether the use of optimal doses of RAS blockade in monotherapy had an influence on the levels of IL-6 in comparison with dual blockade. Method IL-6 levels were measured at baseline and after 4 and 12 months in 70 patients included in the PRONEDI trial (EUDRACT 2004-002470-31), a multicenter, randomized controlled clinical trial. The study included type 2 diabetes patients with a clinical diagnosis of DKD, stage 2 or 3 CKD, and a urinary protein/creatinine ratio (UPCR) >300 mg/g (morning urine spot) on 2 separate opportunities. The primary composite endpoint was a >50% increase in baseline serum creatinine, end stage kidney disease (ESKD) or death. Cox regression model was adjusted for potential confounders or modifiers including eGFR calculated using the CKD-EPI equation and UPCR. Mixed models were adjusted to study longitudinal data. Results The recruitment period was 18 months and the median follow-up was 36 (IQR: 20-48) months, after which 27 patients (38.6%) reached the primary endpoint. At baseline mean IL-6 levels in the whole cohort were 4.58 ± 2.90, at 4 months 4.61 ± 3.10 and at 12 months: 6.14 ± 4.97. Patients were further divided into three groups according to the tertiles of baseline IL-6 levels (tertile 1: 0.65–2.65 pg/mL; tertile 2: 2.66–4.83 pg/mL and tertile 3: 4.84–13.30 pg/mL). There were no differences among the groups in demographic characteristics, cardiovascular risk factors, serum creatinine or proteinuria among the groups. Correlation analyses for IL6 and other inflammatory parameters were carried out for all subjects. The results showed that inflammatory parameters had a significant correlation between them. IL-6 levels correlated with TNFα (r: 0.29; 95% CI: 0.05 - 0.49 p= 0.02), C-reactive protein (r= 0.61; 95%CI: 0.44 - 0.74 p Patients with the highest IL-6 levels (>4.84 pg/ml) experienced a significantly faster evolution to endpoint (mean survival: 33.2 months, CI 95%: 25.2-41.3) than the other 2 groups. In the multivariate Cox regression analysis, the highest levels of IL-6 (Tertile 3) were significantly associated with the primary outcome (HR:3.86; 95%CI: 1.08-13.86) after being adjusted for baseline serum creatinine and proteinuria. The time-dependent area under the ROC curve at two years of follow-up was 0.88 (95% CI: 0.79 - 0.97). The best cut-off IL-6 level was found at 4.68 pg/ml (sensitivity: 100%, specificity: 78.7%) Generalized linear mixed model analysis showed no effect on subsequent IL-6 levels either with RAS blockade monotherapy or dual blockade. Conclusion In conclusion, our results show that higher levels of IL-6 are independently associated with progression of DKD in patients with type 2 diabetes, and that treatment with RAS blockade does not influence these levels. Serum IL-6 may be used as a noninvasive biomarker of progression to ESKD. Since our results show that higher IL-6 levels are associated with a worse renal prognosis, anti- inflammatory drugs that modulate IL-6 could be promising therapeutic agents to improve outcomes. Further studies focusing on the potential applications of anti-IL6 treatment in DKD are warranted.

Background and Aims Thirst mechanism is essential to maintain an adequate osmolarity and homeostasis. During summer heat waves, there is an increased morbidity and mortality in elderly patients that has led to generally recommend an increase in fluid intake in all elderly patients beyond thirst stimulation, even in those independent patients with free access to water. The aim of this study was to observe the differences in calculated serum osmolarity (cOsm) between young, elderly and very elderly patients who were neither institutionalized nor hospitalized, in different seasons throughout the year. Method We conducted a retrospective cross-sectional study in outpatients between 18-104 years old that had undergone a blood test between July 2019 and January 2020, in which serum osmolarity could be calculated. Patients with serum creatinine above 1.5 mg/dl were excluded. Results The study included 45236 blood samples from 41132 patients, 56.1% were female. 50% of patients were between 18 and 65 years old, 45.4% were between 65 and 85 years old and 4.6% were >85 years old. The mean cOsm in patients between 18-65 years was 288.3 mOsm/kg, compared to 289.8 mOsm/kg in those between 65- 85 years old (p85 years, mean cOsm was 289.4 mOsm/kg. When comparing cOsm between different seasons of the year, cOsm in summer months was about 1 mOsm/kg higher than in autumn-winter (288.9 mOsm/kg vs 287.8 mOsm/kg in young patients, p=0.0001; 290.5 mOsm/kg vs 289.4 mOsm/kg in elderly patients, p=0.0001). In the very elderly (>85 years) the difference was smaller and non-significant (289.6mOsm/kg vs 289.1mOsm/kg). Conclusion Under physiologic conditions, patients >65 years have a slightly higher calculated serum osmolarity than younger patients, nevertheless staying within normal range. These differences only increase in 1 mOsm/kg during the summer months. Therefore, it is not indicated to force an increase in fluid intake in the elderly or very elderly population under physiologic conditions.

Background and Aims Proliferative lupus nephritis (class III and IV) is the most severe form of lupus nephritis and requires prompt diagnosis and treatment with immunosuppressive therapy. Since it represents the most serious entity and has the greatest functional consequences there is a need to determine which factors in proliferative lupus nephritis are most predictive of good long-term renal function. Method Methods We analysed the data of 49 biopsy-proven proliferative lupus nephritis (18,4% class III and 81,6% class IV) of three different Spanish hospitals to find prognostic factors for complete renal response (CRR), defined as loss of Results The median follow-up was 8 years (IQR: 3-12,5), during which time 18 patients (36,7 %) achieved CRR. In the univariate analysis complete renal response was related to: (1) at the diagnosis to: age [40,52 (11,29) years vs 29,92 (11,93) p=0,004]; (2) in kidney biopsy to less leukocyte infiltration (42,3% p=0,05); (3) during the follow up to: less comorbities (27,8% vs 64,3% p=0,02), less infections (27,8% vs 58,6% p=0,04) and less hospitalizations due to infections (0% vs 33,3% p=0,010), less prevalence of high BP (22,2% vs 60,7% p=0,01), (4) at the end of follow up to : serum albumin [3,97 (0,59) vs 4,31(0,19) mg/dL p=0,03]. In the logistic regression comorbidies (HR : 5,71 95%IC: 1,56-20,93 p=0,008) and age at the moment of diagnosis (HR : 1,046 95%IC:1,001-1,071 p=0,04) were related to complete renal response. We didn´t find any differences concerning treatments. Conclusion Proliferative lupus nephritis is one of the most severe manifestations of lupus nephritis, resulting in increased morbidity and mortality. Traditionally it has been thought that older patients have a worst prognosis, however we demonstrated that they achieved more frequently CRR. In the management of the patients traditional reno protective measures like strict control of BP must be considered since it is a predictive factor of CRR. We shouldn´t forget about the implications of an aggressive immunosuppressive treatment such as hospitalizations due to infections and comorbities.

Background and Aims Urinary Dickkopf-related protein-3 (DKK3), a stress-induced renal tubular glycoprotein, has been identified as a novel biomarker for chronic kidney disease patients at risk of kidney disease progression. The aim of our study was to assess urinary DKK3 as a diagnostic biomarker for predicting GFR loss and renal survival in a cohort of patients with ANCA-associated vasculitis Method We measured baseline urinary DKK3 levels in a cohort of patients diagnosed with ANCA-associated vasculitis (AAV), and repeated measurements at 1 and 3 months of diagnosis. Urinary DKK3 levels were normalized to urinary creatinine concentrations to account for dilution of the urine. The association between baseline uDKK3/creatinine levels and the rate of GFR loss was measured. The primary composite outcome was defined as an increase of >50% in baseline serum creatinine, initiation of renal replacement therapy or death. Results We included 36 AAV patients with a mean age 71.2 ±12.0 years, 55.6% males, with baseline eGFR at diagnosis 22.3 ±14.1 ml/min. There was a correlation between baseline DKK3-creatinine levels and age (r=0.48, p=0.003) and baseline eGFR (r=-0.327, p=0.051). Ten patients (27.8%) reached the primary composite outcome. Patients were then stratified into two groups according to baseline uDKK3 levels. The group of patients with baseline uDKK3-Creatinine >16000 pg/mg were older (76±12.5 vs 66.4 years, p=0.014), presented a lower baseline eGFR (16.2±10.8 vs 28.5±14.5 ml/min, p=0.007) and had higher baseline uCD163 levels (1135.1 [312.4-2537.5] vs 397.2 [146-809.4], p=0.089]). There were no differences in baseline proteinuria, microhematuria or histological class across the groups. After a median follow-up of three years, 44.4% of the patients in the highest DKK3 group reached the primary composite outcome, whereas only 11.1% of those with lower DKK3 levels reached the endpoint at the end of follow-up (p=0.026) . The area under the time-dependent curve for predicting the primary composite outcome according to uDKK3 was 0,677, with a sensibility of 80% and specificity of 61.5% at the cutoff 16056 pg/mg. Additionally, patients who had a >30% increase in uDKK3 levels after one month reached the primary composite outcome more often (40%) than those who remained with a stable or decreasing DKK3 levels (0%, p=0.04). There were no differences in the rate of change in DKK3 and the different treatment regimens. Conclusion Elevated urinary DKK3 levels help identify those patients who are at a higher risk of kidney disease progression and dialysis dependency over the next three years in ANCA-associated vasculitis. DKK3 monitoring could be considered in the follow-up of these patients to assess the effect of treatment and predict the long-term response.

Background and Aims Vitamin K antagonists (VKA) are the most widely used anticoagulants in the daily clinical practice for the prevention of thrombotic events. Several renal adverse effects have been associated with the use of VKA, from hemodynamic effects due to massive urological hemorrhage associated with VKA overdose, to non-hemodynamic effects that include glomerular hemorrhage and renal tubular obstruction due to red cell casts. The main aim of our study was to establish an association between INR levels and microscopic hematuria in patients with VKA, and identify possible risk and protective factors associated with development of microscopic hematuria in these patients. Method We performed a transversal study that included patients with oral anticoagulation with coumarin derivatives (warfarin or acenocoumarol), that attended the Hematology outpatient clinic from October to December 2019 for routine INR control. A urine specimen was collected on the day of the INR control. We performed a simple urinalysis to all patients and quantified the precise number of red cells in the urine sediment by flow cytometry. Demographic data, kidney function tests including serum creatinine and albuminuria, comorbidities, anticoagulant dose and concomitant treatment were registered. Results 337 patients were included in the study, with an average age of 68.6 ± 12.2 years, 51% were females, 95% were treated with acenocoumarol and 5% with warfarin. Median INR levels were 2.6 (IQR 2.1-3.3) and the median number of urine red cells in the sediment were 11 RBCs/µl (IQR 0-13). 11.9% of the patients presented microscopic hematuria (≥14 RBCs/µl). There was a significant correlation between INR levels and the number of RBCs in the urine sediment (Spearman’s rho= 0.119, p= 0.029), independent from the type of anticoagulant used. This correlation was stronger after excluding those patients who had concomitant bacteriuria (Spearman’s rho= 0.201, p= 0.024). We found no correlation between time elapsed from start of anticoagulation or total weekly dose with the intensity of microscopic hematuria. In the univariate analysis, microhematuria was associated with having an INR >3.5 (19% vs. 10.2%, p=0.046), bacteriuria (15.2% vs. 3.6%, p=0.015), leukocyturia (14.8% vs. 6.6%, p= 0.026), hypertension (16.2% vs. 9.5%, p=0.053), and the use of RAAS blockers (17.2% vs. 6.9%, p=0.004). After performing a multivariate logistic regression that included the aforementioned variables, the association between microhematuria and RAAS blockade with either an ACE inhibitor or ARB was maintained (OR 0.38, CI 95% 0.163-0.886, p=0.025), independent from INR levels, hypertension, leukocyturia or bacteriuria. We found no association between serum creatinine, albuminuria or antiplatelet treatment with the presence of microscopic hematuria. Conclusion INR overdose is significantly associated with the presence of microscopic hematuria, independent from the type of VKA used or the total weekly dose. RAAS blockade is an independent protective factor for the presence of microscopic hematuria in anticoagulated patients.

The coronavirus disease 2019 (COVID-19) pandemic has created major challenges for all countries around the globe. Retrospective studies have identified hypertension, cardiovascular disease, diabetes and older age as risk factors for high morbidity and mortality from COVID-19. There is a general concern that patients with immune-mediated kidney diseases, namely those on immunosuppressive therapies and/or those with more advanced kidney failure, could particularly be at risk for adverse outcomes due to a compromised antiviral immunity. Uncertainties exist on how management routines should be reorganized to minimize the risk of severe acute respiratory syndrome coronavirus 2 infection and what measures are necessary for infected patients. The aim of the present review of the Immunonephrology Working Group of the European Renal Association–European Dialysis and Transplant Association is to provide recommendations for the management of patients with immune-mediated kidney diseases based on the available evidence, similar circumstances with other infectious organisms and expert opinions from across Europe. Such recommendations may help to minimize the risk of encountering COVID-19 or developing complications during COVID-19 in patients with immune-mediated kidney disease.

Background and Aims Obesity is a strong risk factor for the development of chronic kidney disease (CKD) through its close association with hypertension and diabetes. As metabolic demands increase with higher body mass indices, a compensatory glomerular hyperfiltration occurs to meet the increasing burden, consequently increasing intraglomerular pressure that can lead to the development of CKD and may influence the progression of already established kidney damage. The aim of our study was to determine whether there was an association between body mass index (BMI) and kidney disease progression in patients with primary glomerulonephritides (GN). Method We performed a single-centre retrospective cohort study in patients with biopsy-proven primary glomerular disease [minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and IgA nephropathy (IgAN)] diagnosed between July 1998 and December 2018. We excluded patients with no available data on weight at presentation or height, and those lost to follow-up. Patients were stratified into three groups according to BMI to 30 kg/m2. Baseline characteristics were compared between the groups, serum creatinine, proteinuria and microscopic hematuria were recorded at presentation, and yearly afterwards until the end of follow-up. We compared among BMI groups the mean yearly change in eGFR, and yearly increase in proteinuria. Renal adverse outcomes were: time to doubling serum creatinine and initiation of renal replacement therapy (RRT). We performed a multivariate survival analysis to evaluate the risk factors associated with a renal composite outcome that included doubling serum creatinine and initiation of RRT. Results We included 178 patients that presented with a biopsy-proven primary glomerular disease (18 patients with MCD, 38 had FSGS, 38 MN and 84 IgAN), with a mean age of 50.6±18.0 years, 71.3% were males, mean BMI of 28.2±5.4 kg/m2. There were no differences in age at presentation, sex or BMI between the four groups of GN. 24.2% of patients had BMI 30 kg/m2 (obese group). Non-obese group had lower baseline systolic and diastolic blood pressure than the overweight group (p=0.021 and p=0.015) and the obese group (p=0.001 and p Conclusion BMI at presentation was associated with higher blood pressure, but not with baseline serum creatinine or proteinuria, and was not associated with an increased risk of progression of kidney disease in primary glomerular diseases.

Background and Aims IgM nephropathy (IgMN) is a controversial clinicopathological entity that is characterized by the presence of dominant diffuse mesangial IgM deposits, with diverse clinical presentations and varying response to supportive or immunosuppressive treatment. The aim of our study was to determine the clinical features, histopathological characteristics and treatment outcomes in patients with IgMN. Method We conducted a multicenter retrospective observational study that included patients that had undergone a kidney biopsy between January 1990 and December 2018. We identified 40 patients with mesangial proliferative glomerulopathy with dominant IgM deposits. Patients with the presence of systemic diseases (systemic lupus erythematosus, rheumatoid arthritis, diabetes mellitus or paraproteinemia) were excluded, as well as those with incomplete histological or follow-up data. Demographic, clinical, analytical, and histological data were collected, and the different treatment regimens were compared for achieving clinical remission and prevention of kidney disease progression. Results 33 patients were identified with primary mesangial IgM nephropathy, with a median post-biopsy follow-up of 7.3 (2.8-11.1) years. Mean age of presentation was 34.9±19.0 years, 51.5% were females. The most frequent initial manifestation was nephrotic syndrome in 54.5% of cases, followed by proteinuria with microscopic hematuria in 21.2%, proteinuria in 19.1%, and isolated microhematuria in 3% of patients. On presentation, mean eGFR measured by CKD-EPI was 102.9±38.9 ml/min, median proteinuria was 3.3 g/24h (IQR 1.13-4.88), 69.7% had microscopic hematuria and 27.3% presented with hypertension. Light microscopy revealed mesangial hypercellularity and expansion in 81.8% and 78.8% respectively, 6.6% showed extracapillary proliferation, 33.3% showed segmental sclerosis, 39.4% had mild to moderate interstitial fibrosis, and 46.9% had vascular hyaline deposits. On immunofluorescence all patients showed diffuse mesangial IgM deposits, along with subdominant mesangial deposits of IgG (6.1%), IgA (6%), C3 (39.4%), C1q (27.3%) and Lambda (3%). In nephrotic patients, 16.7% were steroid-resistant, whereas 40% of steroid-sensitive patients were steroid-dependent. 41.7% of steroid-sensitive and nondependent IgMN patients developed a median 3.5 relapses during follow-up. 12 nephrotic patients (3 steroid-resistant and 9 steroid-dependent) received immunosuppressive treatment; 5 patients were initially treated with oral cyclophosphamide, 5 with a calcineurin inhibitor (CNI) and 2 with chlorambucil. All steroid-dependent or resistant patients treated with cyclophosphamide or chlorambucil achieved partial or complete clinical remission. Out of the five patients treated with a CNI, 3 attained remission whereas the other two were switched to cyclophosphamide and chlorambucil respectively after which remission was obtained. No patients progressed to end-stage kidney disease. Conclusion IgMN is a rare mesangial proliferative glomerulopathy with a varying clinical and morphological spectrum. It commonly presents as nephrotic syndrome, and is frequently associated with microscopic hematuria. Clinical course is variable, with frequent relapses and a high prevalence of steroid dependence. Complete remission can be achieved with immunosuppressive therapy in cases of steroid-dependent or resistant IgMN, particularly with cytotoxic agents.

Background Although tacrolimus is recommended by KDIGO Clinical Practice Guideline for Glomerulonephritis for the treatment of idiopathic membranous nephropathy (MN), little is known about factors that influence response and relapse of the disease after tacrolimus therapy. Methods Multicentre study that collected 122 MN patients with nephrotic syndrome and stable renal function treated with tacrolimus. Duration of treatment was 17.6 ± 7.2 months, including a full-dose and a tapering period. Results The percentage of remission was 60, 78 and 84% after 6, 12 and 18 months of treatment, respectively. The amount of proteinuria at baseline significantly predicted remission, the lower the baseline proteinuria the higher the probability of remission. Only 10 patients (8%) received concomitantly corticosteroids, and their rate of remission was similar (80% at 18 months). Among responders, 42% achieved complete remission (CR) and 58% partial remission (PR). Almost half (44%) of the responder patients relapsed. The amount of proteinuria at the onset of tacrolimus tapering was significantly higher in relapsing patients. By multivariable analysis, the presence of a PR versus CR at the onset of tacrolimus tapering and a shorter duration of the tapering period significantly predicted relapses. Tolerance was good and the number of adverse events low. Conclusions Tacrolimus monotherapy is an effective and safe option for the treatment of MN with stable renal function. Relapses are frequent in patients with PR and can be partially prevented by a longer tapering period.