Immunosuppressive treatment results in patients with primary IgA nephropathy in Turkiye; the data from TSN-GOLD working group.

BACKGROUND: Immunoglobulin A (IgA) nephropathy (IgAN) treatment consists of maximal supportive care and, for high-risk individuals, immunosuppressive treatment (IST). There are conflicting results regarding IST. Therefore, we aimed to investigate IST results among IgAN patients in Turkiye. METHOD: The data of 1656 IgAN patients in the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases Study Group were analyzed. A total of 408 primary IgAN patients treated with IST (65.4% male, mean age 38.4 ± 12.5 years, follow-up 30 (3-218) months) were included and divided into two groups according to treatment protocols (isolated corticosteroid [CS] 70.6% and combined IST 29.4%). Treatment responses, associated factors were analyzed. RESULTS: Remission (66.7% partial, 33.7% complete) was achieved in 74.7% of patients. Baseline systolic blood pressure, mean arterial pressure, and proteinuria levels were lower in responsives. Remission was achieved at significantly higher rates in the CS group (78% vs. 66.7%, p = 0.016). Partial remission was the prominent remission type. The remission rate was significantly higher among patients with segmental sclerosis compared to those without (60.4% vs. 49%, p = 0.047). In the multivariate analysis, MEST-C S1 (HR 1.43, 95% CI 1.08-1.89, p = 0.013), MEST-C T1 (HR 0.68, 95% CI 0.51-0.91, p = 0.008) and combined IST (HR 0.66, 95% CI 0.49-0.91, p = 0.009) were found to be significant regarding remission. CONCLUSION: CS can significantly improve remission in high-risk Turkish IgAN patients, despite the reliance on non-quantitative endpoints for favorable renal outcomes. Key predictors of remission include baseline proteinuria and specific histological markers. It is crucial to carefully weigh the risks and benefits of immunosuppressive therapy for these patients.

Determinants of non-diabetic kidney diseases in type 2 diabetic patients: Twenty years of single center experience.

BACKGROUND: Diabetic nephropathy is one of the most common complications associated with diabetes. However, non-diabetic kidney disease has been reported in patients with type 2 diabetes at varying incidence rates. The objective of our study is to investigate the occurrence, clinicopathological characteristics, and inflammatory markers linked to diabetic and non-diabetic nephropathy (NDN) in patients with type 2 diabetes mellitus (DM). Additionally, we aimed to explore the possibility of identifying non-diabetic pathology using different biopsy indications. MATERIALS AND METHODS: A total of 159 patients with type 2 DM who underwent renal biopsy at a tertiary care nephrology clinic between January 2000 and January 2022 were enrolled in the study. We collected comprehensive data, including patient demographics, co-morbidities, diabetes duration, renal biopsy indications and results, serological markers, renal function, diabetic retinopathy (DRP), full blood count, blood biochemistry, urinalysis, and inflammatory markers. Patients were categorized based on their biopsy indications, and their biopsy results were classified into three groups: isolated NDN, isolated diabetic nephropathy (DN), and mixed nephropathy with concurrent NDN. We evaluated the relationship between biopsy indications and accompanying pathologies and statistically assessed the likelihood of each biopsy indication detecting non-diabetic renal pathology. Additionally, differences in other data, including demographic and laboratory results and medical histories, among the three groups were investigated. RESULTS: The most frequent indication of renal biopsy was atypical presentations of nephrotic syndrome or nephrotic range proteinuria (ANS/ANP) in 25.1% of patients. Other indications included unexplained renal failure (URF) in 22.6%, atypical presentations of non-nephrotic range proteinuria (ANNP) in 18.2%, acute kidney injury or rapidly progressive kidney dysfunction (AKI/RPKD) in 16.9%, microscopic hematuria in 15.7%, URF with ANNP in 11.3%, and severe nephrotic range proteinuria (SNP) in 9.4%. Renal biopsy revealed isolated NDN in 64.8%, DN in 25.1%, and mixed nephropathy in 10.1% of patients. Primary glomerular diseases were the main non-diabetic renal pathology, predominantly focal segmental glomerulosclerosis (FSGS) (36.4%) followed by MN (10.6%) and IgA nephropathy (7.5%). In comparison with the isolated DN and mixed nephropathy groups, patients in the isolated NDN group had significantly shorter diabetes duration, fewer DRP, as well as lower serum creatinine and neutrophil-to-lymphocyte ratio (NLR). Multivariate logistic regression analysis revealed that presence of hematuria (OR 4.40; 95% CI 1.34 - 14.46, p = 0.014), acute nephrotic range proteinuria (OR 11.93; 95% CI 1.56 - 90.77, p = 0.017), and AKI/APKD (OR 41.08; 95% CI 3.40 - 495.39, p = 0.003) were strong predictors of NDN. Lower NLR (OR 0.77; 95% CI 0.60 - 0.98, p = 0.035), shorter duration of diabetes (OR 0.90; 95% CI 0.84 - 0.97, p = 0.010), and absence of DRP (OR 0.35; 95% CI 0.12 - 0.98, p = 0.046) were also found to be independent indicators of NDN. Receiver operating characteristic curve (ROC) analysis revealed a cut-off value of ≤ 3.01 for NLR (sensitivity of 63.1%, specificity of 63.5%) with regards to predicting non-diabetic renal pathology (p = 0.006). CONCLUSION: Renal biopsy findings in patients with type 2 DM highlight that the prevalence of NDN may be higher than assumed, as presented mainly in the form of primary glomerular disease. The presence of AKI/RPKD, hematuria, and ANS/ANP serves as a reliable indicator of non-diabetic renal pathology. In more ambiguous situations, factors such as a shorter duration of diabetes, absence of DRP, and a lower NLR value may assist clinicians in biopsy decision.

Could mesangial C3 deposition be an independent prognostic marker in immunoglobulin A nephropathy?

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is a common primary glomerulonephropathy. There is evidence that mesangial C3 deposition plays a role in the development of the disease. The aim of this study was to examine the effect of C3 deposition on the prognosis of IgAN patients. METHOD: The study included 1135 patients with biopsy-confirmed IgAN from the database of the Turkish Nephrology Association Glomerular Diseases Working Group (TSN-GOLD). Patients were excluded from the study if they were aged < 18 or > 75 years or if C3 staining had not been performed in the immunofluorescent analysis. C3 deposition was defined as an immunofluorescence intensity of C3 ≥ 2 + within the mesangium. The primary endpoints were the development of end-stage renal disease, a 30% decrease in glomerular filtration rate compared to the basal value or an elevation in proteinuria to a nephrotic level (3.5 gr/day). RESULTS: Mesangial C3 deposition was observed in 603 (53.1%) patients. No statistically significant difference was found at baseline between the groups with and without mesangial C3 deposition, as for age, sex, BMI, proteinuria level, or the presence of hypertension. In the follow-up period with a mean duration of 78 months, no significant difference was found between the two groups regarding the primary endpoints (p = 0.43). A significant correlation between C3 deposition and segmental glomerulosclerosis (S1) according to the Oxford MEST-C classification was found (p = 0.001). CONCLUSION: Although a correlation was observed between mesangial C3 deposition and the S1 MEST-C classification, mesangial C3 deposition was not a prognostic factor in IgAN.

Peritoneal dialysis related non-infectious complications: A single-center experience over 20 years.

OBJECTIVES: Non-infectious complications of peritoneal dialysis (NICPD) are common and could be an important cause of technical failure, especially in the early period of peritoneal dialysis (PD) initiation. NICPD are also center- and provider-dependent. This study aimed to investigate the frequency, etiology, and associated outcomes of NICPD in a single center over a period of 20 years. MATERIALS AND METHODS: Data were retrospectively collected in 262 patients who were initiated on PD between April 2001 and April 2021. Inclusion criteria were age 18 years or older and a minimum follow-up period of 3 months. Patients were grouped according to the reason of NICPD: catheter-related, increased intra-abdominal pressure-related, metabolic, and other complications. RESULTS: There were 142 females and 120 males in the study, with a mean age of 44 ± 16.9 years. The mean time on PD was 52.6 ± 40 months. During the follow-up period, 185 (71%) patients experienced 382 NICPD episodes. 26 patients (9.9%) were switched to maintenance hemodialysis (HD) due to NICPD. Outflow failure was the most common NICPD (n = 97). It was also the most common reason for catheter revision (n = 23) and PD discontinuation (n = 12). Catheter intervention was required in 32 patients (12.2%). Prior HD treatment and male gender were independent risk factors for NICPD and catheter-related complications (OR 2.076; p = 0.037; OR: 1.797, p = 0.042, respectively). Early-start PD was associated with a lower risk for NICPD development (OR: 0.393, p = 0.013). CONCLUSION: In this select cohort of PD patients, we found that NICPD are common and outflow failure is the most common cause of NICPD. NICPD are associated with major complications requiring catheter removal or transfer to in-center HD. Early recognition and appropriate management of NICPD are essential to prolonging time on PD in end-stage renal disease patients.

Post-COVID-19 outcomes of non-dialysis dependent chronic kidney disease patients: a national, multicenter, controlled study.

PURPOSE: Coronavirus disease 2019 (COVID-19) has a higher mortality in the presence of chronic kidney disease (CKD). However, there has not been much research in the literature concerning the outcomes of CKD patients in the post-COVID-19 period. We aimed to investigate the outcomes of CKD patients not receiving renal replacement therapy. METHODS: In this multicenter observational study, we included CKD patients with a GFR < 60 ml/min/1.73 m2 who survived after confirmed COVID-19. Patients with CKD whose kidney disease was due to diabetic nephropathy, polycystic kidney disease and glomerulonephritis were not included in this study. CKD patients with similar characteristics, who did not have COVID-19 were included as the control group. RESULTS: There were 173 patients in the COVID-19 group and 207 patients in the control group. Most patients (72.8%) were treated as inpatient in the COVID-19 group (intensive care unit hospitalization: 16.7%, acute kidney injury: 54.8%, needing dialysis: 7.9%). While there was no significant difference between the baseline creatinine values of the COVID-19 group and the control group (1.86 and 1.9, p = 0.978, respectively), on the 1st month, creatinine values were significantly higher in the COVID-19 group (2.09 and 1.8, respectively, p = 0.028). Respiratory system symptoms were more common in COVID-19 patients compared to the control group in the 1st month and 3rd month follow-ups (p < 0.001). Mortality at 3 months after the diagnosis of COVID-19 was significantly higher in the COVID-19 group than in the control group (respectively; 5.2% and 1.4%, p:0.037). Similarly, the rate of patients requiring dialysis for COVID-19 was significantly higher than the control group (respectively; 8.1% and 3.4%, p: 0.045). CONCLUSIONS: In CKD patients, COVID-19 was associated with increased mortality, as well as more deterioration in kidney function and higher need for dialysis in the post-COVID-19 period. These patients also had higher rate of ongoing respiratory symptoms after COVID-19.

Factors Associated with Long-Term Survival in Maintenance Hemodialysis Patients: A 5-Year Prospective Follow-Up Study.

Objectives: In addition to an increase in the prevalence of dialysis treatments for end-stage renal disease worldwide, the mortality rates among patients on maintenance hemodialysis remain higher than that of the general population. This study aims to evaluate factors associated with long-term survival in stable maintenance hemodialysis patients. Methods: A total of 100 patients initiating hemodialysis by February 2013 were included in this prospective cross-sectional 5-year follow-up study. Data on patient demographics, anthropometric-nutritional parameters, systolic and diastolic blood pressure levels, and hemodialysis parameters, including etiology of kidney failure, hemodialysis duration, peritoneal dialysis history, relative interdialytic weight gain (RIDWG), and Kt/V, were recorded. Results: Overall 5-year survival rate was 56.6%. The 5-year survival rate was higher in patients with younger age (71.4% below median vs. 42.0% above median, p=0.023), lower systolic (63.3 vs. 50%, respectively, p=0.005) and diastolic (62.5 vs. 51.0%, respectively, p=0.02) blood pressure levels, higher Kt/V (46.9 vs. 66.0%, respectively, p=0.044), lower RIDWG (54.0 vs. 32.7%, respectively, p=0.026), and lower serum leptin levels (63.3 vs. 50.0%, respectively, p=0.047). Cox-regression analysis revealed that only systolic blood pressure (B = 1.081, 95% CI, 0.152 to 0.756, p=0.08) was a significant risk factor for poor survival. Conclusion: Our findings revealed pre-dialysis systolic blood pressure as the sole risk factor for poor long-term survival in stable maintenance hemodialysis patients. Malnutrition-inflammation, measures of nutrition, inflammation, and anemia had no significant impact on long-term survival.

The relationship between glomerular IgG staining and poor prognostic findings in patients with IgA nephropathy: the data from TSN-GOLD working group.

BACKGROUND: Galactose-deficient IgA1 (Gd-IgA1) has an increased tendency to form immunocomplexes with IgG in the serum, contributing to IgAN pathogenesis by accumulating in the glomerular mesangium. Several studies showed that glomerular IgG deposition in IgAN is an important cause of mesangial proliferation and glomerular damage. This study aims to determine the association of the positivity of IgG and the intensity of IgG staining with a poor renal prognosis. METHODS: A total of 943 IgAN patients were included in the study. Glomerular IgG staining negative and positive patients were compared using Oxford classification scores, histopathological evaluations, proteinuria, eGFR, albumin, blood pressures. IgG positive patients were classified as (+), (++), (+++) based on their staining intensity, and the association with the prognostic criteria was also evaluated. RESULTS: 81% (n = 764) of the patients were detected as IgG negative, while 19% (n = 179) were positive. Age, gender, body mass index, blood pressure, proteinuria, eGFR, uric acid values were similar in IgG positive and negative patients who underwent biopsy (p > 0.05). Intensity of glomerular IgG positivity was not found to be associated with diastolic and systolic blood pressure, urea, uric acid, age, eGFR, albumin, proteinuria (p > 0.05 for all, r = - 0.084, r = - 0.102, r = - 0.006, r = 0.062, r = 0.014, r = - 0.044, r = - 0.061, r = - 0.066, r = 0.150, respectively). There was no difference for histopathological findings between IgG (+), IgG (++), IgG (+++) groups (for all, p > 0.05). CONCLUSION: Glomerular IgG negativity and positivity detected by routine IFM in IgAN patients is not associated with poor renal prognostic risk factors.

Characteristics and outcomes of hospitalised older patients with chronic kidney disease and COVID-19: A multicenter nationwide controlled study.

OBJECTIVE: Older adults with co-morbidities have been reported to be at higher risk for adverse outcomes of coronavirus disease 2019 (COVID-19). The characteristics of COVID-19 in older patients and its clinical outcomes in different kidney disease groups are not well known. METHODS: Data were retrieved from a national multicentric database supported by Turkish Society of Nephrology, which consists of retrospectively collected data between 17 April 2020 and 31 December 2020. Hospitalised patients aged 18 years or older with confirmed COVID-19 diagnosis suffering from stage 3-5 chronic kidney disease (CKD) or on maintenance haemodialysis (HD) treatment were included in the database. Non-uraemic hospitalised patients with COVID-19 were also included as the control group. RESULTS: We included 879 patients [388 (44.1%) female, median age: 63 (IQR: 50-73) years]. The percentage of older patients in the CKD group was 68.8% (n = 188/273), in the HD group was 49.0% (n = 150/306) and in the control group was 30.4% (n = 70/300). Co-morbidities were higher in the CKD and HD groups. The rate of presentation with severe-critical disease was higher in the older CKD and HD groups (43.6%, 55.3% and 16.1%, respectively). Among older patients, the intensive care unit (ICU) admission rate was significantly higher in the CKD and HD groups than in the control group (38.8%, 37.3% and 15.7%, respectively). In-hospital mortality or death and/or ICU admission rates in the older group were significantly higher in the CKD (29.3% and 39.4%) and HD groups (26.7% and 30.1%) compared with the control group (8.6% and 17.1%). In the multivariate analysis, in-hospital mortality rates in CKD and HD groups were higher than control group [hazard ratio (HR): 4.33 (95% confidence interval [CI]: 1.53-12.26) and HR: 3.09 (95% CI: 1.04-9.17), respectively]. CONCLUSION: Among older COVID-19 patients, in-hospital mortality is significantly higher in those with stage 3-5 CKD and on maintenance HD than older patients without CKD regardless of demographic characteristics, co-morbidities, clinical and laboratory data on admission.

Comparison of lung ultrasound and other volumetric methods in peritoneal dialysis patients.

ABSTRACT: Although many alternative methods are present, maintaining ideal volume status in peritoneal dialysis (PD) patients still rely on clinical evaluation due to lack of an evidence-based method. Lung ultrasound (LUS) is a new method for evaluation of hidden congestion in this group.LUS findings and its relationship with other volumetric methods are investigated in this observational cross-sectional study.In this observational cross sectional study, LUS was performed to all PD patients and compared with symptoms of hypervolemia, physical examination, vascular endothelial growth factor-C (VEGF-C), and N-terminal pro-brain natriuretic peptide levels, chest radiography, echocardiography, bioelectrical impedance analysis.Data of 21 PD patients were evaluated. There was correlation between number of B lines and VEGF-C levels (r = 0.447, P = .042), daily urine output (r = 0.582, P = .007) and left ventricle mass index (r = -0.456, P = .038). Correlations with all other parameters were not significant. Daily urine output and VEGF-C levels were significantly different when B lines were grouped into 2 according to the median level (P < .05 for all).This is the widest spectrum study looking for LUS findings and other volumetric parameters in a small PD cohort. LUS might be useful to evaluate hidden hypervolemia. Its correlation with VEGF-C level is a novel finding.

Frequency of depressive symptoms in Syrian refugees and Turkish maintenance hemodialysis patients during COVID-19 pandemic.

INTRODUCTION: Pneumonia of unknown cause was detected on 30 December 2019 in China. It was categorized as an outbreak and named as COVID-19 by the World Health Organization. The pandemic affects all people, but patient groups such as hemodialysis (HD) patients have been particularly affected. We do not know if refugees suffered more during the outbreak. In this study, we compared depressive symptom frequency between Syrian refugee HD patients and Turkish ones. METHODS: The study had a single-center, cross-sectional design. Demographic and clinical data were collected retrospectively from patients' files containing details about past medical history, demographic variables and laboratory values. Validated Turkish and Arabic forms of Beck Depression Inventory (BDI) were used to assess depressive symptoms. BDI scores were compared according to nationality, demographic features and clinical data. A BDI score more than 14 was accepted as suspicion of depression. RESULTS: 119 patients were enrolled in the study. After the exclusion of 22 patients, 75 Turkish and 22 Syrian patients were included for further analysis. The median BDI (interquartile range) score for Turkish and Syrian patients were 12 (7-23) and 19.5 (12.7-25.2), respectively (p = 0.03). Suspicion of depression was present at 42.7% of Turkish, and 72.7% of Syrian HD patients (p = 0.013). Regarding all patients, phosphorus level, Kt/V, and nationality were significantly different between patients with and without suspicion of depression (p = 0.023, 0.039, 0.013, respectively). CONCLUSION: Syrian patients had higher BDI scores and more depressive symptoms than Turkish patients. Additional national measures for better integration and more mental support to Syrian HD patients are needed.

Clinical significance of glomerular C3 deposition in primary membranous nephropathy.

BACKGROUND: We aimed to investigate the effects of glomerular C3 deposition on clinical, histopathological features, and outcomes of patients with primary membranous nephropathy (MN). METHODS: A total of 261 patients with biopsy-proven primary MN, who were on follow up for at least 6 months, were included in the study. The patients were grouped according to their C3 immunostaining in kidney biopsy samples at the time of diagnosis: Low intensity [LI; (C3 1 +)] and high intensity [HI; (C3 2 + or C3 3 +)]. The primary outcome was the development of kidney failure. Complete (CR) or partial remission (PR) was defined as secondary outcome. RESULTS: Sixteen patients reached the primary outcome after a median follow-up of 33.8 months. Patients in the high intensity group (119 cases) had lower eGFR and higher proteinuria at admission and last follow-up compared to patients in the low intensity group (142 cases). Also, more patients in the high intensity group reached the primary outcome compared to patients in the low intensity group: twelve patients (10.1%) in the high intensity group and four patients (2.8%) in the low intensity group reached the primary outcome (p = 0.015). Kaplan-Meier analysis demonstrated that patients in the high intensity group had a higher risk for kidney failure (p = 0.02). In multivariate logistic regression analysis, high intensity C3 deposition and initial estimated glomerular filtration rate (eGFR) indepenently predicted primary outcome. CONCLUSION: Extensive glomerular C3 deposition is a predictor of kidney failure in patients with MN.

Characteristics of primary glomerular diseases patients with hematuria in Turkey: the data from TSN-GOLD Working Group.

PURPOSE: Hematuria is one of the most common laboratory findings in nephrology practice. To date, there is no enough data regarding the clinical and histopathologic characteristics of primary glomerular disease (PGD) patients with hematuria in our country. METHODS: Data were obtained from national multicenter (47 centers) data entered into the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database between May 2009 and June 2019. The data of all PGD patients over the age of 16 years who were diagnosed with renal biopsy and had hematuria data were included in the study. Demographic characteristics, laboratory and biopsy findings were also recorded. RESULTS: Data of 3394 PGD patients were included in the study. While 1699 (50.1%) patients had hematuria, 1695 (49.9%) patients did not have hematuria. Patients with hematuria had statistically higher systolic blood pressure, serum blood urea nitrogen, creatinine, albumin, levels and urine pyuria. However, these patients had statistically lower age, body mass index, presence of hypertension and diabetes, eGFR, 24-h proteinuria, serum total, HDL and LDL cholesterol, and C3 levels when compared with patients without hematuria. Hematuria was present 609 of 1733 patients (35.8%) among the patients presenting with nephrotic syndrome, while it was presented in 1090 of 1661 (64.2%) patients in non-nephrotics (p < 0.001). CONCLUSION: This is the first multicenter national report regarding the demographic and histopathologic data of PGD patients with or without hematuria. Hematuria, a feature of nephritic syndrome, was found at a higher than expected in the PGDs presenting with nephrotic syndrome in our national database.

Demographic, clinical and laboratory characteristics of rapidly progressive glomerulonephritis in Turkey: Turkish Society of Nephrology-Glomerular Diseases (TSN-GOLD) Working Group.

BACKGROUND: In our study, diagnostic and demographic characteristics of patients diagnosed with RPGN by biopsy, clinical and laboratory findings in our country were investigated. METHODS: Data were obtained from the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group database. Demographic characteristics, indications for biopsy, diagnosis of the glomerular diseases, comorbidities, laboratory and biopsy findings of all patients were recorded. According to their types, RPGN patients were classified as type 1 (anti-GBM related), type 2 (immuncomplex related) and type 3 (pauci-immune). RESULTS: Of 3875 patients, 200 patients with RPGN (mean age 47.9 ± 16.7 years) were included in the study which constitutes 5.2% of the total glomerulonephritis database. Renal biopsy was performed in 147 (73.5%) patients due to nephritic syndrome. ANCA positivity was found in 121 (60.5%) patients. Type 1 RPGN was detected in 11 (5.5%), type 2 RPGN in 42 (21%) and type 3 RPGN in 147 (73.5%) patients. Median serum creatinine was 3.4 (1.9-5.7) mg/dl, glomerular filtration rate was 18 (10-37) ml/min/1.73m2 and proteinuria 2100 (1229-3526) mg/day. The number of crescentic glomeruli ratio was ratio 52.7%. It was observed that urea and creatinine increased and calcium and hemoglobin decreased with increasing crescentic glomerular ratio. CONCLUSIONS: Our data are generally compatible with the literature. Advanced chronic histopathological findings were prominent in the biopsy of 21 patients. Early biopsy should be performed to confirm the diagnosis of RPGN and to avoid unnecessary intensive immunosuppressive therapy. In addition to the treatments applied, detailed data, including patient and renal survival, are needed.

Mortality analysis of COVID-19 infection in chronic kidney disease, haemodialysis and renal transplant patients compared with patients without kidney disease: a nationwide analysis from Turkey.

BACKGROUND: Chronic kidney disease (CKD) and immunosuppression, such as in renal transplantation (RT), stand as one of the established potential risk factors for severe coronavirus disease 2019 (COVID-19). Case morbidity and mortality rates for any type of infection have always been much higher in CKD, haemodialysis (HD) and RT patients than in the general population. A large study comparing COVID-19 outcome in moderate to advanced CKD (Stages 3-5), HD and RT patients with a control group of patients is still lacking. METHODS: We conducted a multicentre, retrospective, observational study, involving hospitalized adult patients with COVID-19 from 47 centres in Turkey. Patients with CKD Stages 3-5, chronic HD and RT were compared with patients who had COVID-19 but no kidney disease. Demographics, comorbidities, medications, laboratory tests, COVID-19 treatments and outcome [in-hospital mortality and combined in-hospital outcome mortality or admission to the intensive care unit (ICU)] were compared. RESULTS: A total of 1210 patients were included [median age, 61 (quartile 1-quartile 3 48-71) years, female 551 (45.5%)] composed of four groups: control (n = 450), HD (n = 390), RT (n = 81) and CKD (n = 289). The ICU admission rate was 266/1210 (22.0%). A total of 172/1210 (14.2%) patients died. The ICU admission and in-hospital mortality rates in the CKD group [114/289 (39.4%); 95% confidence interval (CI) 33.9-45.2; and 82/289 (28.4%); 95% CI 23.9-34.5)] were significantly higher than the other groups: HD = 99/390 (25.4%; 95% CI 21.3-29.9; P < 0.001) and 63/390 (16.2%; 95% CI 13.0-20.4; P < 0.001); RT = 17/81 (21.0%; 95% CI 13.2-30.8; P = 0.002) and 9/81 (11.1%; 95% CI 5.7-19.5; P = 0.001); and control = 36/450 (8.0%; 95% CI 5.8-10.8; P < 0.001) and 18/450 (4%; 95% CI 2.5-6.2; P < 0.001). Adjusted mortality and adjusted combined outcomes in CKD group and HD groups were significantly higher than the control group [hazard ratio (HR) (95% CI) CKD: 2.88 (1.52-5.44); P = 0.001; 2.44 (1.35-4.40); P = 0.003; HD: 2.32 (1.21-4.46); P = 0.011; 2.25 (1.23-4.12); P = 0.008), respectively], but these were not significantly different in the RT from in the control group [HR (95% CI) 1.89 (0.76-4.72); P = 0.169; 1.87 (0.81-4.28); P = 0.138, respectively]. CONCLUSIONS: Hospitalized COVID-19 patients with CKDs, including Stages 3-5 CKD, HD and RT, have significantly higher mortality than patients without kidney disease. Stages 3-5 CKD patients have an in-hospital mortality rate as much as HD patients, which may be in part because of similar age and comorbidity burden. We were unable to assess if RT patients were or were not at increased risk for in-hospital mortality because of the relatively small sample size of the RT patients in this study.

Pentraxin-2 is Associated with Renal Fibrosis in Patients Undergoing Renal Biopsy.

OBJECTIVES: Progressive renal disease is characterized by histological changes in the kidney and fibrosis is a common outcome. Renal biopsy is the only diagnostic tool to evaluate these histopathological changes. Pentraxin-2 (PTX-2) is an anti-inflammatory constitutive plasma protein associated with the innate immune system. Recently, as a biomarker, the circulating level of PTX-2 is shown to be decreased in chronic fibrotic diseases. In this study, we aimed to investigate the relationship between renal fibrosis severity and serum PTX-2 levels in patients undergoing renal biopsy. METHODS: This cross-sectional study included 45 patients and 16 healthy individuals (HIs). The severity of renal fibrosis was evaluated according to the Banff and Sethi scoring systems by the same pathologist. PTX-2 was measured by an enzyme-linked immunosorbent assay and compared with the demographical, clinical, biochemical, and histopathological data of the patients and HIs. RESULTS: PTX-2 levels were lower in the biopsy group than in the HI group (p=0.12). Patients with moderate renal fibrosis had significantly lower serum PTX-2 levels than those in patients with minimal and mild fibrosis (p=0.017 and p=0.010, respectively). PTX-2 concentrations were correlated with serum albumin (r=0.30, p=0.016), and were negatively correlated with serum creatinine levels (rho=-0.42, p=0.01) and body mass index (r=-0.32, p=0.011). CONCLUSIONS: The results indicated that PTX-2 levels are significantly lower in patients with renal fibrosis than HIs, and declining further in patients with severe fibrosis.

A familial Mediterranean fever patient with double homozygous mutations treated with anakinra after kidney transplantation / Un paciente con poliserositis familiar recurrente con mutaciones homocigóticas dobles tratado con anakinra tras un trasplante renal

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Unexpectedly High Prevalence of Low Alpha-Galactosidase A Enzyme Activity in Patients with Focal Segmental Glomerulosclerosis.

OBJECTIVES: Fabry disease (FD) is a rare disease associated with sphingolipid accumulation. Sphingolipids are components of plasma membranes that are important in podocyte function and accumulate in various glomerular diseases such as focal segmental glomerulosclerosis (FSGS). Both FD and FSGS can cause podocyte damage and are classified as podocytopathies. In this respect, FD and FSGS share the same pathophysiologic pathways. Previous screening studies have shown that a significant proportion of end-stage renal disease (ESRD) patients receiving hemodialysis (HD) have unsuspected FD, and the prevalence of low alpha-galactosidase A (αGLA) enzyme activity in these patients is higher than that in the normal population. We aimed to compare αGLA enzyme activity in patients with biopsy-proven FSGS and ESRD receiving HD. METHODS: The records of 232 patients [62 FSGS (F/M: 33/29); 170 HD (M/F: 93/79)] were evaluated retrospectively. The screening was performed based on the αGLA enzyme activity on a dried blood spot, with the confirmation of plasma LysoGb3 levels, and the known GLA mutations were tested in patients with low enzyme activities. The two groups were compared using these parameters. RESULTS: The mean level of αGLA enzyme activity was found to be lower in FSGS patients than in the HD group (2.88±1.2 µmol/L/h versus 3.79±1.9 µmol/L/h, p<0.001). There was no significant relationship between the two groups with regard to the plasma LysoGb3 levels (2.2±1.22 ng/ml versus 1.7±0.66 ng/ml, p: 0.4). In the analysis of GLA mutations, a D313Y mutation [C(937G>T) in exon p] was found in one patient from the FSGS group. CONCLUSIONS: We found that αGAL activity in patients with FSGS is lower than that in patients undergoing HD. The low enzyme activity in patients with FSGS may be explained by considering the similar pathogenesis of FSGS and FD, which may also lead to sphingolipid deposition and podocyte injury.

Amyloid A Amyloidosis After Renal Transplantation: An Important Cause of Mortality.

BACKGROUND: There are limited data on the outcome of transplant recipients with familial Mediterranean fever (FMF)-associated AA amyloidosis. The aim of the present study is to evaluate demographic, clinical, laboratory, and prognostic characteristics and outcome measures of these patients. METHODS: Eighty-one renal transplant recipients with FMF-associated AA amyloidosis (group 1) and propensity score-matched transplant recipients (group 2, n = 81) with nonamyloidosis etiologies were evaluated in this retrospective, multicenter study. Recurrence of AA amyloidosis was diagnosed in 21 patients (group 1a), and their features were compared with 21 propensity score-matched recipients with FMF amyloidosis with no laboratory signs of recurrence (group 1b). RESULTS: The risk of overall allograft loss was higher in group 1 compared with group 2 (25 [30.9%] versus 12 [14.8%]; P = 0.015 [hazard ratio, 2.083; 95% confidence interval, 1.126-3.856]). Patients in group 1 were characterized by an increased risk of mortality compared with group 2 (11 [13.6%] versus 0%; P = 0.001 [hazard ratio, 1.136; 95% confidence interval, 1.058-1.207]). Kaplan-Meier analysis revealed that 5- and 10-year patient survival rates in group 1 (92.5% and 70.4%) were significantly lower than in group 2 (100% and 100%; P = 0.026 and P = 0.023, respectively). Although not reaching significance, overall, 5- and 10-year graft survival rates (57.1%, 94.7%, and 53.8%, respectively) in group 1a were worse than in group 1b (76.2%, 95%, and 77.8%, respectively; P = 0.19, P = 0.95, and P = 0.27, respectively). CONCLUSIONS: AA amyloidosis is associated with higher risk of mortality after kidney transplantation. Inflammatory indicators should be monitored closely, and persistent high levels of acute-phase reactants should raise concerns about amyloid recurrence in allograft.

Comparison of Circulating Levels of Uremic Toxins in Hemodialysis Patients Treated with Medium Cut-Off Membranes and High-Flux Membranes: Theranova in Sisli Hamidiye Etfal (THE SHE) Randomized Control Study.

INTRODUCTION: Removal of uremic toxins is a main objective of hemodialysis; however, whether high-flux and medium cut-off (MCO) membranes differ as regards removal of middle and large uremic toxins is not clear. OBJECTIVE: To compare medium cut-off and high-flux dialyzers as regards their intra- and interdialysis effect on circulating levels of middle and large uremic toxins and serum albumin. METHODS: Fifty-two patients were randomized to have hemodialysis with either 3 months of high-flux dialyzer followed by 3 months of MCO or vice versa. Blood samples were taken before and after dialysis at the first and last sessions of each dialyzer for analyses of middle and large uremic toxins including inflammatory mediators and vascular endothelial growth factor (VEGF), and serum albumin. RESULTS: Reduction rates were higher, and postdialysis levels of ß-2 microglobulin, free kappa and lambda light chains, and myoglobulin were lower at the first and last sessions with MCO dialyzers compared to high-flux dialyzers (p < 0.05 for all). Last session predialysis levels of ß-2 microglobulin, free kappa light chain, and free lambda light chain were lower than first session predialysis levels in MCO dialyzers as compared to high-flux dialyzers (p < 0.05 for all). Last session levels of interleukin-6, interleukin-10, interleukin-17, and interferon-gamma did not differ between dialyzers (p > 0.05 for all). VEGF level was lower in the MCO group compared to the high-flux group (p = 0.043). Last session level of serum albumin with MCO dialyzers was lower than that with high-flux dialyzers (3.62 [3.45-3.88] vs. 3.78 [3.58-4.02] g/L) (p = 0.04) and 6.7% lower (p < 0.001) than at the first session of MCO dialyzers. CONCLUSION: The decline in circulating levels of several middle and large uremic toxins including VEGF following hemodialysis was more pronounced when using MCO membranes as compared to high-flux membranes while their effect on inflammatory molecules was similar.

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis.

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10-12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk.