Chemerin, TNF - α and the degree of albuminuria in patients with diabetic kidney disease.

BACKGROUND: Chronic inflammation has been increasingly recognized as an essential pathogenic mechanism for the development and progression of diabetic kidney disease (DKD). Chemerin is an adipokine which has been suggested to be related to inflammation and has been correlated with the development of diabetic complications. We aimed to explore the potential links between chemerin, TNF - α, as a marker of systemic inflammation, and the level of albuminuria in patients with type 2 diabetes mellitus (T2DM). METHOD: The study included 84 patients with T2DM and 10 normoalbuminuric non-diabetic controls. Demographic, clinical and laboratory data including chemerin and TNF-α levels were collected. RESULTS: A total of 84 diabetic patients were enrolled, 32 males (38.1 %), with mean age 57.9 ± 10.7 years. They were divided into 3 groups: A1: 14 with normalbuminuria, A2: 27 with microalbuminuria, and A3: 43 with macroalbuminuria (uACR < 30, 30-300 and > 300 mg/gm respectively). Chemerin and TNF-α levels increased with the progress of albuminuria (control: 21.3 (14.7 -77), A1: 794 (683-925), A2: 1150 (962.9 - 1221.5) and A3: 1466 (1197.5 - 2002.5) ng/ml; p < 0.001) and (control: 77.9 (59 - 96.8), A1: 85.2 (71-116.3), A2: 87.3 (81 - 97.5) and A3: 99 (85.1 - 142.5) pg/ml; p = 0.009) respectively. Among the diabetics, a significant association was evident between serum chemerin and serum TNF-α (r = 0.53; p < 0.001). On linear stepwise regression analysis, chemerin was significantly associated with TNF-α and HbA1c (unstandardized ß 10.881 and 272.68 respectively, p < 0.001); and TNF-α was significantly correlated with chemerin, uACR (unstandardized ß 0.059 and 0.004 respectively, p < 0.001) and HbA1c (unstandardized ß -13.699, p = 0.014). CONCLUSION: Our findings suggest a potential role of chemerin and TNF-α in the development and progression of DKD, and thus support the role of the inflammatory pathway. Larger follow up studies are warranted to further explore the potential links between chemerin, inflammation and DKD.

Real-world safety and effectiveness of retreatment of Egyptian chronic hepatitis C patients not responding to NS5A inhibitor-based therapies.

The aim of this study was to assess the efficacy and safety of two protocols for retreatment of a cohort of Egyptian patients with chronic hepatitis C (CHC) who relapsed after NS5A inhibitor-based therapy. We conducted a prospective cohort study to assess the safety and efficacy of 12 weeks' retreatment with either combination of sofosbuvir/daclatasvir/simeprevir plus ribavirin (SOF/DCV/SMV/RBV, n = 45) or sofosbuvir/ombitasvir/paritaprevir/ritonavir plus ribavirin (SOF/OBV/PTV/r/RBV, n = 163) in patients who had previously failed NS5A inhibitors-based regimens. The primary end point was SVR 12 weeks after the end of treatment (SVR12). Safety follow-up data were recorded for 60 weeks after the end of treatment. Two hundred-eight patients were included in the study. Of them, 53.4% of patients were females and 40.4% had liver cirrhosis. The most common prior drug combinations were sofosbuvir/daclatasvir (n = 94) and sofosbuvir/daclatasvir plus ribavirin (n = 109). The overall SVR12 rates were 98.1%. In SOF/DCV/SMV/RBV group, 95.6% achieved SVR12, while in SOF/OBV/PTV/r/RBV group, the SVR12 rates were 98.8%. SVR12 was higher in cirrhotic patients (84/84) than noncirrhotic (120/124), P value = .0149. Regarding the safety outcomes, anaemia and fatigue were significantly higher in SOF/OBV/PTV/r/RBV group. Hepatocellular carcinoma (HCC) was reported in eight (3.8%) patients (four in each group). Of them, death was confirmed in four patients. Retreatment of Egyptian CHC relapsed patients with either sofosbuvir/daclatasvir/simeprevir plus ribavirin or sofosbuvir/ombitasvir/paritaprevir/ritonavir plus ribavirin is highly effective and well-tolerated for both noncirrhotic and compensated cirrhotic patients. Incidental de novo HCC and hepatic decompensation are comparable in the two groups.

Epidemiology and impact of bloodstream infections among kidney transplant recipients: A retrospective single-center experience.

BACKGROUND: Bloodstream infection (BSI) represents an important source of morbidity and mortality, as well as an increasing therapeutic challenge, among solid organ transplant recipients. Understanding the epidemiological and microbiological characteristics of BSI following renal transplantation is paramount to the implementation of appropriate preventative and therapeutic measures. METHODS: We conducted a retrospective review of all BSI episodes occurring between July 2009 and April 2016 in adult patients, who received a renal transplant at Royal Free London hospital. RESULTS: A total of 116 episodes of BSI occurred in 87 patients, 43 (49.4%) of them men. The mean age at BSI was 54.37 ± 12.81 years. Late-onset BSI (>12 months post transplant) represented 55.2%, with the median time to BSI being 16.28 month. Sixty-seven patients had single BSI and 20 had recurrent episodes. Enterobacteriaceae were responsible for 73.7% of BSI, with Escherichia coli the commonest causative organism (46.6%). The urinary tract was the most frequent source of infection in 56.9%. Among the E. coli infections, 100% of the tested isolates were sensitive to meropenem, ertapenem, tigecycline, and fosfomycin, and >90% were sensitive to piperacillin-tazobactam, amikacin, and colistin. Lower susceptibility rates were encountered for ceftriaxone (70.6%), amoxicillin-clavulanic acid (48.1%), cotrimoxazole (40.4%), trimethoprim (37.3%), and amoxicillin (21.6%). During BSI, the median serum creatinine increased from a reference of 131 µmol/L to a peak of 219 µmol/L. Acute kidney injury (AKI) complicated 75/116 BSI episodes (64.7%)-stage 1: 34, stage 2: 31, and stage 3 AKI: 10 episodes. After 3 months, the median creatinine remained elevated at 146 µmol/L. The 3-month mortality rate was 8% (7/87), and the death-censored graft loss was 6.9% (6/87). No significant difference was seen between BSI of urinary and non-urinary sources in the incidence of AKI (χ2  = 0.24, P = .6) or the percentage of creatinine change between baseline and peak and 3-month creatinines (P = .2 and .7 respectively). CONCLUSIONS: Urinary tract infection remains the commonest source of systemic infection among kidney transplant recipients and resistance to commonly used frontline antibiotics is common; thus, prevention and early detection are paramount. The appropriate choice of initial empirical antibiotic is vital to improve the outcome. Each unit needs to understand the epidemiology of organisms causing BSI in their transplant patients and their antibiotic susceptibilities.

Effective treatment with rituximab for the maintenance of remission in frequently relapsing minimal change disease.

AIM: Treatment of frequently relapsing or steroid-dependent minimal change disease (MCD) in children and adults remains challenging. Glucocorticoids and/or other immunosuppressive agents are the mainstay of treatment, but patients often experience toxicity from prolonged exposure and may either become treatment dependent and/or resistant. Increasing evidence suggests that rituximab (RTX) can be a useful alternative to standard immunosuppression and allow withdrawal of maintenance immunosuppressants; however, data on optimal treatment regimens, long-term efficacy and safety are still limited. METHODS: We undertook a prospective study of RTX to allow immunosuppression minimization in 15 young adults with frequently relapsing or steroid-dependent, biopsy-proven MCD. All patients were in remission at the start of treatment and on a calcineurin inhibitor. Two doses of RTX (1 gr) were given 6 months apart. A subset of patients also received an additional dose 12 months later, in order to examine the benefit of re-treatment. Biochemical and clinical parameters were monitored over an extended follow-up period of up to 43 months. RESULTS: Median steroid-free survival after RTX was 25 months (range 4-34). Mean relapse frequency decreased from 2.60 ± 0.28 to 0.4 ± 0.19 (P < 0.001) after RTX. Seven relapses occurred, five of which (71%) when CD19 counts were greater than 100 µ. Immunoglobulin levels remained unchanged, and no major side effects were observed throughout the follow-up period. CONCLUSIONS: Rituximab therapy is effective at maintaining prolonged steroid-free remission and reducing relapse frequency in this group of patients. Our study lends further support for the role of RTX in the treatment of patients with frequently relapsing or steroid-dependent MCD.

The successful treatment of mpox with brincidofovir in renal transplant recipients-a report of 2 cases.

An mpox outbreak was declared in July 2022 by the world health organization (WHO). It causes a mild self-limiting disease however; in immunosuppressed hosts, it tends to cause severe disseminated infection. Most cases of mpox in sold organ transplant (SOT) recipients reported in the literature were treated with tecovirimat. Here we report two cases of severe disseminated mpox infection in renal transplant recipients that were successfully treated with brincidofovir. Both patients were discharged from the hospital with no immediate significant side effects from brincidofovir reported until the submission of this report.

Parathormone enhances eryptosis in patients with end stage renal disease treated by hemodialysis.

INTRODUCTION: Parathormone (PTH) and phosphorus, which are considered as uremic toxins, are associated with reduced red cell survival, yet with unproven mechanism. We aimed to assess the relation between PTH and phosphorus levels and eryptosis in patients with CKD5d treated by hemodialysis. METHODS: In a cohort of 85 patients with CKD5d treated by conventional hemodialysis, the percent of annexin V-binding RBCs was assessed by flow cytometry to indicate the percent of eryptotic RBCs. FINDINGS: The median percent of annexin V-binding RBCs was 2.3 (1.4-4.7)%. On linear regression analysis, PTH was independently associated with the percent of annexin V-binding RBCs (ß = 0.003; 95% CI: 0.002-0.004; p < 0.001). The percent of annexin V-binding RBCs differed significantly in patients with low PTH (<150 pg/mL; 27/85, 31.8%), target PTH (150-600 pg/mL; 32/85, 37.6%), and high PTH (>600 pg/mL; 26/85, 30.6%) groups (1.24 [0.65-1.85]; 2.46 [1.73-4.05]; and 4.82 [3.45-5.61]%, respectively; p < 0.001). Considering the tertiles of the percent of annexin V binding RBCs, PTH increased significantly from 85 (50.6-273) in the 1st to 298.3 (172.8-606.8) in the 2nd and 827.6 (357.4-1171.3) pg/mL in the 3rd tertiles (p < 0.001). Phosphorus and calcium levels as well as the CaxPh product were similar among the three tertiles (p > 0.05). DISCUSSION: Patients with CKD5d express high rates of eryptosis. PTH excess in those patients may result in further eryptosis enhancement, and this represents a potential pathogenic mechanism linking hyperparathyroidism with the anemia of CKD.

The difference between delivered and prescribed dialysate sodium in haemodialysis machines.

BACKGROUND: The choice of dialysate sodium (DNa) for haemodialysis (HD) patients remains controversial, with some studies reporting that a lower DNa improves blood pressure control and reduces intradialytic weight gain. Studies on DNa depend on the alignment of programmed to delivered DNa. We wished to determine whether there were differences between programmed and delivered DNa. METHODS: Dialysate samples were obtained from three dialysis machines: Fresenius 4008H (F4008H) and 5008S (F5008S) and B-Braun hemodiafiltration (HDF) Dialog+(BB). DNa was measured by indirect ion-selective electrode (ISE), flame photometry (FP) and ion chromatography (IC) at different DNa concentrations. RESULTS: We tested 18 F5008S, 18 F4008H and 31 BB machines over 153 HD treatments. The median measured minus programmed DNa was significantly greater with the BB machine [ISE, 7 (6-8); FP, 7 (6-8); IC, 6 (5-7)], followed by the F4008H [ISE, 5.5 (5-7); FP, 4 (2.25-5.75); IC, 4 (2-5)]and F5008S [ISE, 4 (2-5); FP, 1 (-1-1.75); IC, 1 (-0.5 to 2)] mEq/L (P < 0.05). At higher programmed DNa (140-145 mEq/L), measured DNa was greater for the BB and F4008 machines by all methods (P < 0.05), but only by ISE for the F5008 (P < 0.05). CONCLUSIONS: We noted a systematic bias in DNa delivery with measured DNa being greater than that programmed by our HD machines. The magnitude of the bias varied between machines and with DNa. Our results may help explain the diverse results reported in studies of DNa.

Outcomes following kidney transplantation in patients with sickle cell disease: The impact of automated exchange blood transfusion.

There are over 12,000 people with sickle cell disease (SCD) in the UK, and 4-12% of patients who develop Sickle Cell Nephropathy (SCN) progress to End Stage Renal Disease (ESRD). Renal transplantation offers the best outcomes for these patients with but their access to transplantation is often limited. Regular automated exchange blood transfusions (EBT) reduce the complications of SCD and may improve outcomes. However, concerns over alloimmunisation limit its widespread implementation. In this retrospective multicenter study, data were collected on 34 SCD patients who received a kidney transplant across 6 London Hospitals between 1997 and 2017. 20/34 patients were on an EBT program, pre or post renal transplantation. Overall patient and graft survival were inferior to contemporaneous UK data in the ESRD population as a whole, a finding which is well-recognised. However, patient survival (CI 95%, p = 0.0032), graft survival and graft function were superior at all time-points in those who received EBT versus those who did not. 4/20 patients (20%) on EBT developed de novo donor specific antibodies (DSAs). 3/14 patients (21%) not on EBT developed de novo DSAs. The incidence of rejection in those on EBT was 5/18 (28%), as compared with 7/13 (54%) not on EBT. In conclusion, our data, while limited by an inevitably small sample size and differences in the date of transplantation, do suggest that long-term automated EBT post renal transplant is effective and safe, with improvement in graft and patient outcomes and no increase in antibody formation or graft rejection.

The use of sirolimus in patients with recurrent cytomegalovirus infection after kidney transplantation: A retrospective case series analysis.

Cytomegalovirus (CMV) is one of opportunistic infections post solid organ transplant and remains a cause of morbidity and mortality. Mammalian target of rapamycin inhibitors has a theoretical antiviral advantage compared to conventional immunosuppression. The primary outcome was to assess the viremic response and kidney function in a cohort of kidney transplant recipients (KTRs) with difficult to manage CMV infection when converted to sirolimus. We retrospectively analyzed the outcome of substituting sirolimus for mycophenolate mofetil (MMF) or tacrolimus in 18 KTR with difficult to manage, resistant/recurrent CMV viremia unresponsive or intolerant of standard anti-CMV treatment, or immunosuppression reduction. Safety and feasibility of sirolimus conversion were assessed through studying CMV viral loads, creatinine levels, immunosuppression, antiviral therapy, kidney function, and acute rejection episodes before and after starting sirolimus as well as the sirolimus side effects. Data were collected from the hospital filing system. The Wilcoxon matched-pairs signed-rank test and Friedman test were used for statistical analysis. The area under the curve for Log10 CMV viral load (log10 copies/ml) was significantly higher before than after the sirolimus switch (P = 0.0156). The median number of days on antiviral treatment was reduced after conversion to sirolimus [48 days (0-95); vs. 68 days (21-146)]. Acute rejection occurred more commonly before than after starting sirolimus [n =5 (27.7%) vs. n = 2 (11.1%)]. Median serum creatinine before conversion to sirolimus was 175.5 µmol/L (79-243), and showed no deterioration three months and one year after conversion [148 (69-271) and 162.5 (69-287) µmol/L, respectively, P = 0.002]. The use of sirolimus, often alongside tacrolimus and after discontinuation of MMF, is a useful strategy in treating recurrent CMV viremia without provoking rejection.

Systemic Endotoxin in Peritoneal Dialysis Patients.

Previous reports linked systemic endotoxemia in dialysis patients to increased markers of inflammation, cardiovascular disease, and mortality. Many peritoneal dialysis (PD) patients use acidic, hypertonic dialysates, which could potentially increase gut permeability, resulting in systemic endotoxemia. However, the results from studies measuring endotoxin in PD patients are discordant. We therefore measured systemic endotoxin in 55 PD outpatients attending for routine assessment of peritoneal membrane function; mean age 58.7 ± 16.4 years, 32 (58.2%) male, 21 (38.2%) diabetic, median duration of PD treatment 19.5 (13 - 31) months, 32 (58.2%) using 22.7 g/L dextrose dialysates, and 47 (85.5%) icodextrin. The median systemic endotoxin concentration was 0.0485 (0.0043 - 0.103) Eu/mL. We found no association between endotoxin levels and patient demographics, markers of inflammation, serum albumin, N-terminal pro-brain natriuretic peptide, extracellular volume measured by bioimpedance, blood pressure, PD prescriptions or peritoneal membrane transporter status, or medications. The measurement of endotoxin can be lowered by failure to effectively release protein-bound endotoxin prior to analysis and increased by contamination when taking blood samples and processing and storing the samples. Additionally, contamination with ß-glucan from fungal cell walls and the use of different assays to analyze endotoxin can also give differing results. These factors may help to explain the disparate results reported in different studies. Our study would suggest that exposure to standard peritoneal dialysates does not substantially increase systemic endotoxin. However, until endotoxin assays can measure free and bound endotoxin separately, the role of endotoxin causing inflammation in PD patients remains to be determined.

Prevalence of occult hepatitis C virus infection in patients who achieved sustained virologic response to direct-acting antiviral agents.

The reappearance of HCV infection months or years after sustained virologic response (SVR) may be due to the persistence of HCV in tissue cells in spite of being undetected in serum. This situation is known as occult hepatitis C infection (OCI). We aimed to assess the prevalence of OCI in Egyptian patients with chronic hepatitis C (CHC) who achieved SVR after treatment with direct-acting antiviral agents (DAA). We carried out a cross-sectional study at the Advanced Center for Liver Diseases of Zagazig University Hospitals and Al-Ahrar Viral Hepatitis Treatment Center, Sharkia Governorate, Egypt. One hundred and fifty adult patients with CHC, who achieved SVR 12-24 weeks after end of treatment with sofosbuvir/daclatasvir ± ribavirin (139 patients, 92.67%), sofosbuvir/ledipasvir ± ribavirin (eight patients, 5.33%), sofosbuvir/simeprevir (two patients, 1.33%), and ombitasvir/ paritaprevir/ritonavir + ribavirin (one patient, 0.67%), according to the Egyptian National Committee for Control of Viral Hepatitis, were included in the study. We tested these patients for HCV RNA in peripheral blood mononuclear cells (PBMCs) immediately after confirmation of SVR12-24 weeks. Statistical analysis was performed by means of the Shapiro-Wilk test, Mann-Whitney U test, Chi-square test, and Fisher's exact test. Seventeen patients (11.33%) were positive for PBMNCs HCV RNA. The prevalence of OCI was highest in patients treated with simeprevir/sofosbuvir (2/2 patients). There is a substantially high prevalence of OCI after treatment with DAAs. We recommend dual testing for HCV RNA in both serum and PBMCs at the end of treatment of HCV infection with DAAs and during validation of the SVR following the initial response.