Introduction Testosterone deficiency is common among hemodialysis (HD) patients. Numerous studies demonstrated a correlation between testosterone levels and body composition in the general population. However, this correlation was not thoroughly investigated in HD patients. Therefore, we conducted this study to assess the correlation between free testosterone levels and body composition in HD patients. Methods A total of 80 males were included in this study, compromising 40 hD males in addition to age-matched 40 healthy controls. Free testosterone levels and body composition were measured using the InBody device. Results Free testosterone level was significantly lower in the HD group (median; 75 pg/dl and interquartile range (IQR); 55.8-87.8 pg/dl) than in the control group (median; 101 pg/dl and IQR 82.8-115 pg/dl) with p = 0.004. The skeletal muscle index (SMI) was significantly lower in the HD group (median; 10.18 and IQ; 9.5-10.6) compared to the control group (median; 11.1 and IQR; 10.3-11.7), with p < 0.001. The lean tissue index (LTI) was significantly lower in the HD group (median; 18.44 and IQ; 17.3-19.3) than in the control group (median; 19.88 and IQ; 18.4-20.8), with p = 0.006. The free testosterone level demonstrated a positive correlation with SMI (r = 0.34, p = 0.03) and LTI (r = 0.33, p = 0.04). Conclusion There is a correlation between free testosterone levels and body composition in HD patients.

Aim: The risk of infection with COVID-19 in hemodialysis (HD) patients is higher compared to the general population. Additionally, HD patients are at higher risk of developing post-COVID-19 infection sequelae. However, this has not been thoroughly investigated. Therefore, we aimed to study the impact of COVID-19 on nutritional status and psychological health in HD patients 6 months following recovery. Materials and methods: We recruited HD patients who were proven to be infected with COVID-19 and received treatment at two HD units in two institutions between April 2022 and December 2022. Additionally, we enrolled a group of age- and sex-matched HD patients who had not previously been infected with COVID-19 or received vaccination. Nutritional status was assessed using malnutrition inflammation score (MIS), while psychological health was assessed using online questionnaires. The Patient Health Questionnaire 9 (PHQ 9) was employed to assess symptoms of depression, the Generalized Anxiety Disorder 7 (GAD 7) was used to identify anxiety disorders, the Patient Health Questionnaire 15 (PHQ 15) was utilized to measure somatic symptoms, and the Insomnia Severity Index (ISI) was used to measure insomnia. Results: A total of 60 subjects (30 patients and 30 controls) were assessed in the study. We found statistically significant differences between patients and controls regarding the MIS (median score (interquartile range (IQR)); 11 (9 - 12) and 5.5 (5 - 7), respectively), PHQ 15 (median score (IQR); 17.5 (15 - 19) and 9 (6 - 11), respectively), PHQ (median score (IQR); 17 (13 - 19) and 5 (7 - 8), respectively), GAD 7 (median score (IQR); 14 (11 - 16) and 6 (4 - 8), respectively), and ISI (median score (IQR); 20 (15 - 22) and (7 - 11), respectively), with p < 0.001 for all scores. Conclusion: COVID-19 has long-term effects on the psychosocial health of HD patients and may lead to a higher incidence of malnutrition 6 months post recovery.

Objectives: Outcomes of therapy for lupus nephritis (LN) are often suboptimal. Guidelines offer varied options for treatment of LN and treatment strategies may differ between clinicians or regions. We aimed to assess variations in the usual practice of UK physicians who treat LN. Methods: We conducted an online survey of simulated LN cases for UK rheumatologists and nephrologists to identify treatment preferences for class IV and class V LN. Results: Of 77 respondents, 48 (62.3%) were rheumatologists and 29 (37.7%) were nephrologists. 37 (48.0%) reported having a joint clinic between nephrologists and rheumatologists, 54 (70.0%) reported having a multi-disciplinary team meeting for LN and 26 (33.7%) reported having a specialised lupus nurse. 58 (75%) of respondents reported arranging renal biopsy before starting the treatment. 20 (69%) of the nephrologists, but only 13 (27%) of rheumatologists, reported having a formal departmental protocol for treating patients with LN (p < 0.001). The first-choice treatment of class IV LN in pre-menopausal patients was mycophenolate mofetil (MMF, 41 [53.2%]), followed by cyclophosphamide (CYC, 15 [19.6%]), rituximab (RTX, 12 [12.5%]) or a combination of immunosuppressive drugs (9 [11.7%]) with differences between nephrologists' and rheumatologists' choices (p = 0.026). For class V LN, MMF was the preferred initial treatment irrespective of whether proteinuria was in the nephrotic range or not. RTX was the preferred 2nd line therapy for non-responders. Conclusion: There was variation in the use of protocols, specialist clinic service provision, biopsies, and primary and secondary treatment choices for LN reported by nephrologists and rheumatologists in the UK.

OBJECTIVES:It is not known why only some hepatitis C virus (HCV) infected patients develop glomerulonephritis (GN). Therefore, we investigated the role of soluble complement regulators in the development of HCV associated GN.METHODS:Patients with HCV associated GN who were admitted to our nephrology unit between July 2016 and July 2018 were recruited to the study (group 1). Two other age and sex matched groups were studied as control groups: patients with HCV without GN (group 2) and healthy HCV negative volunteers (group 3). There were 26 participants in each of the three groups at the end of the recruitment period. An assay of serum fluid-phase complement regulators was performed using enzyme linked immunosorbent assay technique. Three complement single nucleotide polymorphisms (SNPs) were analyzed using real time polymerase chain reaction (Taqman; thermo fisher scientific): rs2230199 and rs1047286 for complement 3 (C3) and rs800292 for complement factor H (CFH).RESULTS:Serum levels of complement 4 binding protein (C4BP) were significantly lower in group 1 (median 70 ng/ml) than in groups 2 (median 88.8 ng/ml) and 3 (median 82.8 ng/ml) with p value of 0.007. The minor allele (allele A) of rs800292 for CFH was significantly higher in group 2 and group 3 (G 54% and A 46%) than in group 1 (G 73% and A 27%), p = 0.04.CONCLUSIONS:Low C4BP levels are associated with GN in HCV infected patients. In addition, rs800292 SNP in CFH protects against GN in patients with HCV.

Background Atherosclerotic renovascular disease (ARVD) often follows an asymptomatic chronic course which may be undetected for many years. However, there are certain critical acute presentations associated with ARVD and these require a high index of suspicion for underlying high-grade RAS (renal artery stenosis) to improve patient outcomes. These acute presentations, which include decompensated heart failure syndromes, accelerated hypertension, rapidly declining renal function, and acute kidney injury (AKI), are usually associated with bilateral high-grade RAS (> 70% stenosis), or high-grade RAS in a solitary functioning kidney in which case the contralateral kidney is supplied by a vessel demonstrating renal artery occlusion (RAO). These presentations are typically underrepresented in large, randomized control trials which to date have been largely negative in terms of the conferred benefit of revascularization. Case presentation Here we describe 9 individual patients with 3 classical presentations including accelerated phase hypertension, heart failure syndromes, AKI and a fourth category of patients who suffered recurrent presentations. We describe their response to renal revascularization. The predominant presentation was that consistent with ischaemic nephropathy all of whom had a positive outcome with revascularization. Conclusion A high index of suspicion is required for the diagnosis of RAS in these instances so that timely revascularization can be undertaken to restore or preserve renal function and reduce the incidence of hospital admissions for heart failure syndromes.

Abstract Background Patients with rapidly declining renal function face the dual threat of end-stage renal disease (ESRD) and mortality prior to ESRD. What is less well characterised is whether the pattern of the renal trajectory, linear or non-linear, unmasks subgroups of rapidly progressing patients that face adverse outcomes in a differential manner. Methods An individual eGFR slope was applied to all outpatient estimated glomerular filtration rate (eGFR) values for each patient in the Salford Kidney Study from 2002 to 2018 who had at least 2 years follow-up, ≥4 eGFR values and baseline eGFR 15 to < 60 ml/min/1.73m2. Rapid progression was defined as an annual eGFR slope of ≤ − 3 ml/min/1.73m2/yr and patients were categorised as linear or non-linear progressors based on the nature of their eGFR-time graphs. A Fine-Gray competing risk hazard model was used to determine factors associated with progression to ESRD and with mortality prior to ESRD. Cumulative incidence function curves highlighted differences in outcomes between linear and non-linear patients. Results There were 211 rapidly deteriorating patients with linear eGFR trajectories and 61 rapid non-linear patients in the study cohort. Factors associated with ESRD included younger age, male gender, lower baseline eGFR and higher serum phosphate, whilst older age, history of myocardial infarction and anaemia predicted mortality prior to ESRD. Over a median follow-up of 3.7 years, linear progressors reached ESRD sooner whilst those with non-linear progression faced significantly higher rates of mortality prior to ESRD. Conclusions Patients with rapid eGFR decline have high rates of adverse outcomes that are differentially expressed in those progressing linearly and non-linearly as a result of differing phenotypic profiles. Consequently, addressing individual risk factor profiles is important to deliver optimal personalised patient care.

Background Elevated oxidant levels and low antioxidant levels in patients with end-stage renal disease (ESRD) play a significant role in the development of endothelial dysfunction, atherogenesis and cardiovascular disease (CVD). A deficiency in vitamin D (Vit.D) is also suggested to be responsible for the generation of oxidative stress (OS) and CVD. Among dialysis patients, conflicting data exist concerning the relationship between hepatitis C virus (HCV) infection and OS. We studied the relationship between 25Vit.D level, HCV infection, and plasma 8 iso-prostaglandin F2 alpha (8-ISO-PGF2 alpha) as an OS marker in an Egyptian hemodialysis (HD) cohort. Methods One hundred and twenty ESRD patients on HD were initially recruited to the study but only 88 patients have met the inclusion and none of the exclusion criteria. Midweek predialysis session blood samples were collected for the measurement of 25(OH) Vit.D, plasma 8-ISO-PGF2 alpha, high sensitivity C - reactive protein (hs-CRP), and intact parathyroid hormone (intact PTH). Patients were stratified into two groups according to the presence or absence of serum antibodies against HCV and their plasma 8-ISO-PGF2 alpha were compared. Results Vit.D deficiency was noted in 93% of the participants; the median 8-ISO-PGF2 alpha level was 382 pg/mL. No significant correlation between Vit.D and 8-ISO-PGF2 alpha levels was found. Thirty-two participants (36%) were HCV+ and their 8-ISO-PGF2 alpha levels were significantly lower relative to in the seronegative group (median 171 vs. 647 pg/mL; P < 0.006). Conclusion In this Egyptian HD cohort, Vit D deficiency was highly prevalent, yet failed to show any correlation with F2-isoprostanes. HCV+ HD patients might be shielded from OS.

Abstract Background Secondary hyperparathyroidism may lead to increased cardiovascular risk. The use of cinacalcet may improve bone and cardiovascular health with improved parathormone (PTH) and phosphate control. Methods This is an open-label prospective randomised controlled trial to compare progression of cardiovascular and chronic kidney disease mineral and bone disorder (CKD-MBD) parameters. Patients were randomised to receive cinacalcet alongside standard therapy or standard therapy alone. Thirty-six haemodialysis patients who had > 90 days on dialysis, iPTH > 300 pg/mL, calcium > 2.1 mmol/L and age 18–75 years were included. Following randomization, all 36 patients underwent an intensive 12-week period of bone disease management aiming for iPTH 150-300 pg/mL. The primary outcome was change in vascular calcification using CT agatston score. Secondary outcomes included pulse wave velocity (PWV), left ventricular mass index (LVMI), carotid intima-media thickness (CIMT), augmentation index (Aix) and bone measurements. The above measurements were obtained at baseline and 12 months. Results There was no evidence of a group difference in the progression of calcification (median change (IQR) cinacalcet: 488 (0 to1539); standard therapy: 563 (50 to 1214)). In a post hoc analysis combining groups there was a mean (SD) phosphate reduction of 0.3 mmol/L (0.7) and median (IQR) iPTH reduction of 380 pg/mL (− 754, 120). Regression of LVMI and CIMT was seen (P = 0.03 and P = 0.001) and was significantly associated with change of phosphate on multi-factorial analyses. Conclusions With a policy of intense CKD-MBD parameter control, no significant benefit in bone and cardiovascular markers was seen with the addition of cinacalcet to standard therapy over one year. Tight control of hyperphosphataemia and secondary hyperparathyroidism may lead to a reduction in LVMI and CIMT but this needs further investigation. Although the sample size was small, meticulous trial supervision resulted in very few protocol deviations with therapy.

Biomarker discovery in the field of risk prediction in chronic kidney disease (CKD) embraces the prospect of improving our ability to risk stratify future adverse outcomes and thereby guide patient care in a new era of personalised medicine. However, many studies that report biomarkers predictive of CKD progression share a key methodological limitation: failure to characterise patients' renal progression precisely. This weakens any observable association between a biomarker and an outcome poorly defined by a patient's change in renal function over time. In this commentary, we discuss the need for a better approach in this research arena and describe a compelling strategy that has the advantage of offering robust and meaningful biomarker exploration relevant to CKD progression.

Objectives The R102G variant in complement 3 (C3) results in two allotypic variants: C3 fast (C3F) and C3 slow (C3S). C3F presents at increased frequency in patients with chronic kidney disease (CKD), our aim is to explore its role in CKD progression and mortality. Methods Delta (Δ) eGFR for 2038 patients in the Salford Kidney Study (SKS) was calculated by linear regression; those with ≤-3ml/min/1.73m2/yr were defined as rapid progressors (RP) and those with ΔeGFR between -0.5 and +1ml/min/1.73m2/yr, labelled stable CKD patients (SP).A group of 454 volunteers was used as a control group. In addition, all biopsy-proven glomerulonephritis (GN) patients were studied regardless of their ΔeGFR. R102G was analysed by real-time PCR, and genotypic and allelic frequencies were compared between RP and SP along with the healthy control group. Results There were 255 SP and 259 RP in the final cohort. Median ΔeGFR was 0.07 vs. -4.7 ml/min/1.73m2/yr in SP vs. RP. C3F allele frequency was found to be significantly higher in our CKD cohort (25.7%) compared with the healthy control group (20.6%); p = 0.008.However, there was no significant difference in C3F allele frequency between the RP and SP groups. In a subgroup analysis of 37 patients with IgA nephropathy in the CKD cohort (21 RP and 16 SP), there was a significantly higher frequency of C3F in RP 40.5% vs. 9.4% in SP; p = 0.003. In the GN group, Cox regression showed an association between C3F and progression only in those with IgA nephropathy (n = 114);HR = 1.9 (95% CI 1.1–3.1; p = 0.018) for individuals heterozygous for the C3F variant, increased further for individuals homozygous for the variant, HR = 2.8 (95% CI 1.2–6.2; p = 0.014). Conclusion The C3 variant R102G is associated with progression of CKD in patients with IgA nephropathy.

BACKGROUND:Tacrolimus dosing immediately posttransplant is based on body weight. Recent studies have highlighted that the dosing of tacrolimus purely based on weight may not be appropriate, particularly in individuals who are obese.OBJECTIVES:This study aimed to estimate the effect of body mass index (BMI) and the weight-based dosing on tacrolimus trough levels in recipients of renal transplants.DESIGN AND PARTICIPANTS:This study was conducted on 400 of the 863 patients registered in the Salford, UK, renal transplant database between 2012 and 2019 who had complete and analysable datasets. Data were collected at baseline (first tacrolimus trough level after transplantation), after 1 month and 6 months posttransplantation. The cohort was split into three groups based on BMI (kg/m2 ; Group 1 ≤ 25, Group 2 > 25-30 and Group 3 > 30) which were compared with respect to tacrolimus dose, plasma levels and concentration/dose (C/D) ratio at the three-time points.RESULTS:Patients in the higher BMI group (Group 3) had significantly higher baseline tacrolimus trough levels despite receiving a lower initiation dose per kilogram of body weight. After 1 and 6-months posttransplant, the higher BMI group were receiving a significantly lower tacrolimus dose relative to their body weight, with a significant negative correlation between body weight and tacrolimus/kg body weight. There was no adverse relationship evident between tacrolimus dosing or concentration and graft function.CONCLUSIONS:Our study showed that standard dosing of tacrolimus based on body weight in individuals who were obese did not adversely affect their tacrolimus concentrations or transplant function.

Background Risk factors predictive of rapid linear chronic kidney disease (CKD) progression and its associations with end-stage renal disease (ESRD) and mortality requires further exploration, particularly as patients with linear estimated glomerular filtration rate (eGFR) trajectory represent a clear paradigm for understanding true CKD progression. Methods A linear regression slope was applied to all outpatient eGFR values for patients in the Salford Kidney Study who had ≥2 years follow-up, ≥4 eGFR values and baseline CKD stages 3a-4. An eGFR slope (ΔeGFR) of ≤ − 4 ml/min/1.73m 2 /yr defined rapid progressors, whereas − 0.5 to + 0.5 ml/min/1.73m 2 /yr defined stable patients. Binary logistic regression was utilised to explore variables associated with rapid progression and Cox proportional hazards model to determine predictors for mortality prior to ESRD. Results There were 157 rapid progressors (median ΔeGFR − 5.93 ml/min/1.73m 2 /yr) and 179 stable patients (median ΔeGFR − 0.03 ml/min/1.73m 2 /yr). Over 5 years, rapid progressors had an annual rate of mortality or ESRD of 47 per 100 patients compared with 6 per 100 stable patients. Factors associated with rapid progression included younger age, female gender, higher diastolic pressure, higher total cholesterol:high density lipoprotein ratio, lower albumin, lower haemoglobin and a urine protein:creatinine ratio of > 50 g/mol. The latter three factors were also predictive of mortality prior to ESRD, along with older age, smoking, peripheral vascular disease and heart failure. Conclusions There is a heterogenous interplay of risk factors associated with rapid linear CKD progression and mortality in patients with CKD. Furthermore, rapid progressors have high rates of adverse outcomes and require close specialist monitoring.