Why do people waste differently on dialysis? Important insights from other chronic diseases with a focus on microRNAs.

Premature muscle tiring (fatigue) is an important complication of advanced kidney disease, and results in a reduced ability to walk and exercise. As patients move from pre-dialysis care to dialysis, they begin to lose their residual kidney function and experience muscle wasting. Not all patients on dialysis are affected equally by the loss of muscle mass, and the effect of dialysis mode (peritoneal dialysis and hemodialysis) on muscle wasting is not known. This review will explore molecular mechanisms relevant to muscle wasting in end-stage kidney disease and in particular address some important insights into the emerging role of microRNAs in regulating the wasting response in individuals with chronic disease.

Increased prevalence of renal cysts in patients with sickle cell disease.

BACKGROUND: Early detection and interventions have enabled patients with sickle cell disease (SCD) to live well into adulthood. Consequently, the chronicity of SCD allows for the insidious manifestation of multisystem complications, including renal damage. Cystic renal lesions are commonly incidentally discovered on ultrasound and computerised tomography (CT) imaging of the abdomen. Most are benign simple cysts, however, difficulties may be encountered if infection, rupture, haemorrhage or cancerous changes develop. We aimed to determine whether patients with SCD have a higher prevalence of simple renal cysts compared to non-SCD individuals. METHODS: Data for a group of 223 patients with SCD who had undergone an ultrasound and/or CT imaging of the abdomen were extracted for comparison with 180 control patients (haemoglobin genotype unknown), matched for age and ethnicity. Scans were evaluated for 198 SCD patients and 180 controls. RESULTS: Renal cysts were found in 58% of the SCD group and 20% of the controls (OR 5.4 (CI 2.6-11.0), RR 2.8 (CI 1.9-4.2)). Bilateral renal cysts were found in 28% of the SCD participants in comparison with 5% of the control group. In those who had one or more cysts identified, the average number of cysts was 3.76 for the SCD group and 1.94 for the controls. Men with SCD were more likely to develop cysts than women (66% vs 53%), as were men without SCD (22% vs 17%). CONCLUSIONS: Simple renal cysts occur more frequently, are more abundant and develop at a younger age in patients with SCD than ethnically-matched controls. Further study of the mechanism underlying cyst formation may shed light on both sickle cell nephropathy and other cystic renal diseases.

Systemic inflammation and oxidative stress contribute to acute kidney injury after transcatheter aortic valve implantation.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication of transcatheter aortic valve implantation (TAVI) and has been linked to preexisting comorbidities, peri-procedural hypotension, and systemic inflammation. The extent of systemic inflammation after TAVI is not fully understood. Our aim was to characterize the inflammatory response after TAVI and evaluate its contribution to the mechanism of post-procedural AKI. METHODS: One hundred and five consecutive patients undergoing TAVI at our institution were included. We analyzed the peri-procedural inflammatory and oxidative stress responses by measuring a range of biomarkers (including C-reactive protein [hsCRP], cytokine levels, and myeloperoxidase [MPO]), before TAVI and 6, 24, and 48 hours post-procedure. We correlated this with changes in renal function and patient and procedural characteristics. RESULTS: We observed a significant increase in plasma levels of pro-inflammatory cytokines (hsCRP, interleukin 6, tumor necrosis factor alpha receptors) and markers of oxidative stress (MPO) after TAVI. The inflammatory response was significantly greater after transapical (TA) TAVI compared to transfemoral (TF). This was associated with a higher incidence of AKI in the TA cohort compared to TF (44% vs. 8%, respectively, p < 0.0001). The incidence of AKI was significantly lower when N-acetylcysteine (NAC) was given peri-procedurally (12% vs. 38%, p < 0.005). In multivariate analysis, only the TA approach and no use of NAC before the procedure were independent predictors of AKI. CONCLUSIONS: TAVI creates a significant post-procedural inflammatory response, more so with the TA approach. Mechanisms of AKI after TAVI are complex. Inflammatory response, hypoperfusion, and oxidative stress may all play a part and are potential therapeutic targets to reduce/prevent AKI.

Flexibility in peritoneal dialysis prescription: Impact on technique survival.

BACKGROUND: Patient burnout is a major cause of technique failure on peritoneal dialysis (PD). Reducing the PD prescription on an individual basis, dependent upon residual kidney function (RKF), may have a role in prolonging time on PD by reducing dialysis burden. This retrospective study aimed to determine the safety and impact of flexible PD prescribing on technique and patient survival. METHODS: All patients (186) from our centre starting PD from 1st January 2012 to 31st December 2016 were included. Data on dialysis prescription were collected for each patient from the time they had started PD, and dialysis adequacy measured regularly (3-6 monthly) using PD Adequest. RESULTS: Median age at start of dialysis was 61 years. Only 49% started on PD 7 days a week and this dropped to 27% at 3 months following the first clearance test. Over 90% achieved creatinine clearance > 50 L/week/1.73 m2 up to 2 years of follow-up, with 87% achieving this standard at 3 years. Patient and technique survival at 1, 2 and 3 years were 91%, 81%, and 72%, and 89%, 87% and 78% respectively. Factors on univariate analysis affecting technique survival included increasing age (HR 0.98, p = 0.04, 95% CI (0.96-0.999)), two or more episodes of PD-associated peritonitis (HR 4.52, p = 0.00, 95% CI (1.87-10.91)) and increasing PD intensity (HR 3.30, p = 0.02, 95% CI (1.22-8.93)). After multivariate adjustment which included baseline kidney function, low PD intensity continued to be associated with better technique survival (HR 0.17, p = 0.03, 95% CI (0.03-0.85)). CONCLUSION: Tailoring the PD prescription to RKF enables days off dialysis while still maintaining recommended levels of small solute clearance. This approach reduces dialysis burden and is associated with higher technique survival.

Central venous stenosis in a transplant patient due to thyroid pathology: A teachable moment.

Central venous stenosis is a well-recognized complication of central venous catheter use in hemodialysis patients, which may present with significant swelling of the upper limbs, neck, and face. Here, we describe a renal transplant recipient previously on hemodialysis, who underwent endovascular intervention for central venous stenosis after presenting with facial swelling and exertional dyspnoea. His symptoms continued to progress, however, until the underlying thyroid pathology was recognized. Ruling out the possible mimics of central venous stenosis is important in preventing unnecessary intervention. This case highlights the role of specialty bias in the process of diagnosis.

Bochdalek hernias associated with intrathoracic kidney: A case report and systematic review of outcomes including renal function.

BACKGROUND: An intrathoracic kidney is a very rare form of ectopic kidney. Though increasingly recognized in the literature, impact on renal function is less well described. We report the case of a 67-year-old South Asian gentleman who presented with intrathoracic kidney and chronic kidney disease. We carried out a systematic review of the available literature on intrathoracic kidney, in order to characterize the typical clinical features, and describe likely clinical course and possible renal and extra-renal complications associated with this form of ectopia. MATERIALS AND METHODS: A structured search using PubMed identified all relevant published case reports from 1988 to 2018, with search restricted to papers in English, and to adult cases only (> 18 years of age). 124 records were identified, and after screening for eligibility, 34 case reports were analyzed. RESULTS: Median age was 53.5 years, with no gender predominance. 68% (27/34) of cases were symptomatic. 29% (10/34) had a significant complication associated with their intrathoracic kidney, with 3 cases with either documented chronic or end-stage kidney disease. 26% (9/34) required surgical intervention. CONCLUSION: Though previously regarded as a benign entity, results from our systematic review, bearing in mind susceptibility to publication bias, suggests an appreciable risk of symptoms, complications, and in the minority a risk to kidney function. We recommend close biochemical and imaging surveillance of affected patients, with low threshold for intervention in those with renovascular stenosis, reflux, or hydronephrosis.

Long-term outcomes in patients with encapsulating peritoneal sclerosis managed with nutritional support.

BACKGROUND: Little is known about long-term survivors with encapsulating peritoneal sclerosis (EPS). Published literature focuses on patients managed surgically. We describe our experience of the long-term outcomes in patients with EPS conservatively managed with nutritional support alone. METHODS: This is a single-centre retrospective observational study of patients who had survived for ≥5 years since diagnosis. EPS survivors were invited for review of symptoms, nutritional assessment and evaluation of quality of life. Radiological progression was assessed based on serial computed tomography (CT) scores for each patient. RESULTS: A total of 23 patients with a diagnosis of EPS for at least 5 years were identified, with 18 patients alive at the time of the study. Of these 18 patients, 10 patients transferred to haemodialysis (HD) and 8 patients received kidney transplants. Commonest symptoms were nausea (91%) and vomiting (73%). Mean body mass index for patients was within the ideal and healthy range, with only 11% suffering from continued weight loss. In all, 70% EPS survivors on HD received nutritional support compared to 15% of those with transplants; 17% required ongoing parenteral nutrition. Of the 11 patients with serial CT scans at least 4 years apart, 10 had an increase in radiological score for EPS but with no apparent correlation to clinical outcomes. There were no significant differences in the reported quality of life between EPS survivors on HD and those transplanted, with self-rated health status equivalent to that reported for the general end-stage kidney disease (ESKD) population. CONCLUSION: Long-term survival following EPS managed conservatively with nutritional support is feasible, with the majority no longer requiring nutritional support and having a quality of life similar to other patients with ESKD.

Predicting long-term renal and patient survival by clinicopathological features in elderly patients undergoing a renal biopsy in a UK cohort.

BACKGROUND: Several publications have demonstrated the use of renal biopsy in elderly patients in establishing a diagnosis and enabling directed therapy. However, evidence on the long-term outcomes following biopsies is lacking. The aim of this study is to describe the renal and patient outcomes in elderly patients according to indication for biopsy, clinical parameters and the histological diagnosis. METHODS: We performed a retrospective cohort study of 463 patients >70 years old who underwent a renal biopsy at our centre between 2006 and 2015. RESULTS: The median age of the patients was 74.8 (range 70.0-89.6) years. The most frequent primary diagnoses were pauci-immune crescentic glomerulonephritis (GN; 12%), acute interstitial nephritis (10.8%) and membranous GN (7.1%). Death-censored renal survival at 1 and 5 years following the index biopsy was 85.2 and 75.9%, respectively, and patient survival at 1 and 5 years was 92.2 and 71.6%, respectively. Patients who progressed to end-stage renal disease (ESRD) were at higher risk of dying compared with patients who did not require dialysis [hazard ratio 2.41 (95% confidence interval 1.58-3.68; P < 0.001]. On multivariate analysis, factors associated with the risk of progression to ESRD were creatinine (P < 0.001), heavy proteinuria (P = 0.002) and a non-chronic kidney disease (CKD) biopsy indication (P = 0.006). A histological diagnosis of primary GN (P = 0.001) or tubulointerstitial nephritis (P = 0.008) was associated with a favourable renal outcome, while patients with vasculitis and paraprotein-related renal disease (PPRD) had the highest risk of requiring dialysis (P = 0.0002 and P = 0.003, respectively). PPRD was also an independent risk factor for death. CONCLUSIONS: This study demonstrates that renal biopsies in the elderly not only enable directed therapy, but also provide prognostic information on renal and patient survival.

Causes and risk factors for acute dialysis initiation among patients with end-stage kidney disease-a large retrospective observational cohort study.

BACKGROUND: Patients who require acute initiation of dialysis have higher mortality rates when compared with patients with planned starts. Our primary objective was to explore the reasons and risk factors for acute initiation of renal replacement therapy (RRT) among patients with end-stage kidney disease (ESKD). Our secondary objective was to determine the difference in glomerular filtration rate (GFR) change in the year preceding RRT between elective and acute dialysis starts. METHODS: We conducted a single-centre retrospective observational study. ESKD patients either started dialysis electively (planned starters) or acutely and were known to renal services for >90 (unplanned starters) or <90 days (urgent starters). RESULTS: In all, 825 consecutive patients initiated dialysis between January 2013 and December 2015. Of these, 410 (49.7%) patients had a planned start. A total of 415 (50.3%) patients had an acute start on dialysis: 244 (58.8%) unplanned and 171 (41.2%) urgent. The reasons for acute dialysis initiation included acute illness (58%) and unexplained decline to ESKD (33%). Cardiovascular disease [n = 30 (22%)] and sepsis [n = 65 (48%)] accounted for the majority of acute systemic illness. Age and premorbid cardiovascular disease were independent risk factors for acute systemic illness among unplanned starts, whereas autoimmune disease accounted for the majority of urgent starts. The rate of decline in GFR was greater in the month preceding RRT among acute dialysis starters compared with planned starters (P < 0.001). CONCLUSIONS: Cardiovascular disease and advancing age were independent risk factors for emergency dialysis initiation among patients known to renal services for >3 months. The rapid and often unpredictable loss of renal function in the context of acute systemic illness poses a challenge to averting emergency dialysis start.