Use of frailty assessment instruments in nephrology populations: a scoping review.

BACKGROUND: Frailty is a clinical syndrome of accelerated aging associated with adverse outcomes. Frailty is prevalent among patients with chronic kidney disease but is infrequently assessed in clinical settings, due to lack of consensus regarding frailty definitions and diagnostic tools. This study aimed to review the practice of frailty assessment in nephrology populations and evaluate the context and timing of frailty assessment. METHODS: The search included published reports of frailty assessment in patients with chronic kidney disease, undergoing dialysis or in receipt of a kidney transplant, published between January 2000 and November 2021. Medline, CINAHL, Embase, PsychINFO, PubMed and Cochrane Library databases were examined. A total of 164 articles were included for review. RESULTS: We found that studies were most frequently set within developed nations. Overall, 161 studies were frailty assessments conducted as part of an observational study design, and 3 within an interventional study. Studies favoured assessment of participants with chronic kidney disease (CKD) and transplant candidates. A total of 40 different frailty metrics were used. The most frequently utilised tool was the Fried frailty phenotype. Frailty prevalence varied across populations and research settings from 2.8% among participants with CKD to 82% among patients undergoing haemodialysis. Studies of frailty in conservatively managed populations were infrequent (N = 4). We verified that frailty predicts higher rates of adverse patient outcomes. There is sufficient literature to justify future meta-analyses. CONCLUSIONS: There is increasing recognition of frailty in nephrology populations and the value of assessment in informing prognostication and decision-making during transitions in care. The Fried frailty phenotype is the most frequently utilised assessment, reflecting the feasibility of incorporating objective measures of frailty and vulnerability into nephrology clinical assessment. Further research examining frailty in low and middle income countries as well as first nations people is required. Future work should focus on interventional strategies exploring frailty rehabilitation.

Outcomes of cinacalcet withdrawal in Australian dialysis patients.

BACKGROUND: Secondary hyperparathyroidism (SHPT) in chronic kidney disease is associated with cardiovascular and bone pathology. Measures to achieve parathyroid hormone (PTH) target values and control biochemical abnormalities associated with SHPT require complex therapies, and severe SHPT often requires parathyroidectomy or the calcimimetic cinacalcet. In Australia, cinacalcet was publicly funded for dialysis patients from 2009 to 2015 when funding was withdrawn following publication of the EVOLVE study, which resulted in most patients on cinacalcet ceasing therapy. We examined the clinical and biochemical outcomes associated with this change at Australian renal centres. AIM: To assess changes to biochemical and clinical outcomes in dialysis patients following cessation of cinacalcet. METHODS: We conducted a retrospective study of dialysis patients who ceased cinacalcet after August 2015 in 11 Australian units. Clinical outcomes and changes in biochemical parameters were assessed over a 24- and 12-month period, respectively, from cessation of cinacalcet. RESULTS: A total of 228 patients was included (17.7% of all dialysis patients from the units). Patients were aged 63 ± 15 years with 182 patients on haemodialysis and 46 on peritoneal dialysis. Over 24 months following cessation of cinacalcet, we observed 26 parathyroidectomies, 3 episodes of calciphylaxis, 8 fractures and 50 deaths. Eight patients recommenced cinacalcet, meeting criteria under a special access scheme. Biochemical changes from baseline to 12 months after cessation included increased levels of serum PTH from 54 (interquartile range 27-90) pmol/L to 85 (interquartile range 41-139) pmol/L (P < 0.0001), serum calcium from 2.3 ± 0.2 mmol/L to 2.5 ± 0.1 mmol/L (P < 0.0001) and alkaline phosphatase from 123 (92-176) IU/L to 143 (102-197) IU/L (P < 0.0001). CONCLUSION: Significant increases in serum PTH, calcium and alkaline phosphatase occurred over a 12-month period following withdrawal of cinacalcet. Longer-term follow up will determine if these biochemical and therapeutic changes are associated with altered rates of parathyroidectomies and cardiovascular mortality and morbidity.

Calcineurin inhibitor withdrawal or tapering for kidney transplant recipients.

BACKGROUND: Calcineurin inhibitors (CNI) can reduce acute transplant rejection and immediate graft loss but are associated with significant adverse effects such as hypertension and nephrotoxicity which may contribute to chronic rejection. CNI toxicity has led to numerous studies investigating CNI withdrawal and tapering strategies. Despite this, uncertainty remains about minimisation or withdrawal of CNI. OBJECTIVES: This review aimed to look at the benefits and harms of CNI tapering or withdrawal in terms of graft function and loss, incidence of acute rejection episodes, treatment-related side effects (hypertension, hyperlipidaemia) and death. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 11 October 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) where drug regimens containing CNI were compared to alternative drug regimens (CNI withdrawal, tapering or low dose) in the post-transplant period were included, without age or dosage restriction. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for eligibility, risk of bias, and extracted data. Results were expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: We included 83 studies that involved 16,156 participants. Most were open-label studies; less than 30% of studies reported randomisation method and allocation concealment. Studies were analysed as intent-to-treat in 60% and all pre-specified outcomes were reported in 54 studies. The attrition and reporting bias were unclear in the remainder of the studies as factors used to judge bias were reported inconsistently. We also noted that 50% (47 studies) of studies were funded by the pharmaceutical industry.We classified studies into four groups: CNI withdrawal or avoidance with or without substitution with mammalian target of rapamycin inhibitors (mTOR-I); and low dose CNI with or without mTOR-I. The withdrawal groups were further stratified as avoidance and withdrawal subgroups for major outcomes.CNI withdrawal may lead to rejection (RR 2.54, 95% CI 1.56 to 4.12; moderate certainty evidence), may make little or no difference to death (RR 1.09, 95% CI 0.96 to 1.24; moderate certainty), and probably slightly reduces graft loss (RR 0.85, 95% CI 0.74 to 0.98; low quality evidence). Hypertension was probably reduced in the CNI withdrawal group (RR 0.82, 95% CI 0.71 to 0.95; low certainty), while CNI withdrawal may make little or no difference to malignancy (RR 1.10, 95% CI 0.93 to 1.30; low certainty), and probably makes little or no difference to cytomegalovirus (CMV) (RR 0.87, 95% CI 0.52 to 1.45; low certainty)CNI avoidance may result in increased acute rejection (RR 2.16, 95% CI 0.85 to 5.49; low certainty) but little or no difference in graft loss (RR 0.96, 95% CI 0.79 to 1.16; low certainty). Late CNI withdrawal increased acute rejection (RR 3.21, 95% CI 1.59 to 6.48; moderate certainty) but probably reduced graft loss (RR 0.84, 95% CI 0.72 to 0.97, low certainty).Results were similar when CNI avoidance or withdrawal was combined with the introduction of mTOR-I; acute rejection was probably increased (RR 1.43; 95% CI 1.15 to 1.78; moderate certainty) and there was probably little or no difference in death (RR 0.96; 95% CI 0.69 to 1.36, moderate certainty). mTOR-I substitution may make little or no difference to graft loss (RR 0.94, 95% CI 0.75 to 1.19; low certainty), probably makes little of no difference to hypertension (RR 0.86, 95% CI 0.64 to 1.15; moderate), and probably reduced the risk of cytomegalovirus (CMV) (RR 0.60, 95% CI 0.44 to 0.82; moderate certainty) and malignancy (RR 0.69, 95% CI 0.47 to 1.00; low certainty). Lymphoceles were increased with mTOR-I substitution (RR 1.45, 95% CI 0.95 to 2.21; low certainty).Low dose CNI combined with mTOR-I probably increased glomerular filtration rate (GFR) (MD 6.24 mL/min, 95% CI 3.28 to 9.119; moderate certainty), reduced graft loss (RR 0.75, 95% CI 0.55 to 1.02; moderate certainty), and made little or no difference to acute rejection (RR 1.13 ; 95% CI 0.91 to 1.40; moderate certainty). Hypertension was decreased (RR 0.98, 95% CI 0.80 to 1.20; low certainty) as was CMV (RR 0.41, 95% CI 0.16 to 1.06; low certainty). Low dose CNI plus mTOR-I makes probably makes little of no difference to malignancy (RR 1.22, 95% CI 0.42 to 3.53; low certainty) and may make little of no difference to death (RR 1.16, 95% CI 0.71 to 1.90; moderate certainty). AUTHORS' CONCLUSIONS: CNI avoidance increased acute rejection and CNI withdrawal increases acute rejection but reduced graft loss at least over the short-term. Low dose CNI with induction regimens reduced acute rejection and graft loss with no major adverse events, also in the short-term. The use of mTOR-I reduced CMV infections but increased the risk of acute rejection. These conclusions must be tempered by the lack of long-term data in most of the studies, particularly with regards to chronic antibody-mediated rejection, and the suboptimal methodological quality of the included studies.

Interventions for treating central venous haemodialysis catheter malfunction.

BACKGROUND: Adequate haemodialysis (HD) in people with end-stage kidney disease (ESKD) is reliant upon establishment of vascular access, which may consist of arteriovenous fistula, arteriovenous graft, or central venous catheters (CVC). Although discouraged due to high rates of infectious and thrombotic complications as well as technical issues that limit their life span, CVC have the significant advantage of being immediately usable and are the only means of vascular access in a significant number of patients. Previous studies have established the role of thrombolytic agents (TLA) in the prevention of catheter malfunction. Systematic review of different thrombolytic agents has also identified their utility in restoration of catheter patency following catheter malfunction. To date the use and efficacy of fibrin sheath stripping and catheter exchange have not been evaluated against thrombolytic agents. OBJECTIVES: This review aimed to evaluate the benefits and harms of TLA, preparations, doses and administration as well as fibrin-sheath stripping, over-the-wire catheter exchange or any other intervention proposed for management of tunnelled CVC malfunction in patients with ESKD on HD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register up to 17 August 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included all studies conducted in people with ESKD who rely on tunnelled CVC for either initiation or maintenance of HD access and who require restoration of catheter patency following late-onset catheter malfunction and evaluated the role of TLA, fibrin sheath stripping or over-the-wire catheter exchange to restore catheter function. The primary outcome was be restoration of line patency defined as ≥ 300 mL/min or adequate to complete a HD session or as defined by the study authors. Secondary outcomes included dialysis adequacy and adverse outcomes. DATA COLLECTION AND ANALYSIS: Two authors independently assessed retrieved studies to determine which studies satisfy the inclusion criteria and carried out data extraction. Included studies were assessed for risk of bias. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using GRADE. MAIN RESULTS: Our search strategy identified 8 studies (580 participants) as eligible for inclusion in this review. Interventions included: thrombolytic therapy versus placebo (1 study); low versus high dose thrombolytic therapy (1); alteplase versus urokinase (1); short versus long thrombolytic dwell (1); thrombolytic therapy versus percutaneous fibrin sheath stripping (1); fibrin sheath stripping versus over-the-wire catheter exchange (1); and over-the-wire catheter exchange versus exchange with and without angioplasty sheath disruption (1). No two studies compared the same interventions. Most studies had a high risk of bias due to poor study design, broad inclusion criteria, low patient numbers and industry involvement.Based on low certainty evidence, thrombolytic therapy may restore catheter function when compared to placebo (149 participants: RR 4.05, 95% CI 1.42 to 11.56) but there is no data available to suggest an optimal dose or administration method. The certainty of this evidence is reduced due to the fact that it is based on only a single study with wide confidence limits, high risk of bias and imprecision in the estimates of adverse events (149 participants: RR 2.03, 95% CI 0.38 to 10.73).Based on the available evidence, physical disruption of a fibrin sheath using interventional radiology techniques appears to be equally efficacious as the use of a pharmaceutical thrombolytic agent for the immediate management of dysfunctional catheters (57 participants: RR 0.92, 95% CI 0.80 to 1.07).Catheter patency is poor following use of thrombolytic agents with studies reporting median catheter survival rates of 14 to 42 days and was reported to improve significantly by fibrin sheath stripping or catheter exchange (37 participants: MD -27.70 days, 95% CI -51.00 to -4.40). Catheter exchange was reported to be superior to sheath disruption with respect to catheter survival (30 participants: MD 213.00 days, 95% CI 205.70 to 220.30).There is insufficient evidence to suggest any specific intervention is superior in terms of ensuring either dialysis adequacy or reduced risk of adverse events. AUTHORS' CONCLUSIONS: Thrombolysis, fibrin sheath disruption and over-the-wire catheter exchange are effective and appropriate therapies for immediately restoring catheter patency in dysfunctional cuffed and tunnelled HD catheters. On current data there is no evidence to support physical intervention over the use of pharmaceutical agents in the acute setting. Pharmacological interventions appear to have a bridging role and long-term catheter survival may be improved by fibrin sheath disruption and is probably superior following catheter exchange. There is no evidence favouring any of these approaches with respect to dialysis adequacy or risk of adverse events.The current review is limited by the small number of available studies with limited numbers of patients enrolled. Most of the studies included in this review were judged to have a high risk of bias and were potentially influenced by pharmaceutical industry involvement.Further research is required to adequately address the question of the most efficacious and clinically appropriate technique for HD catheter dysfunction.

Narrative Review: Clinical Implications and Assessment of Frailty in Patients With Advanced CKD.

Frailty is a multidimensional clinical syndrome characterized by low physical activity, reduced strength, accumulation of multiorgan deficits, decreased physiological reserve, and vulnerability to stressors. Frailty has key social, psychological, and cognitive implications. Frailty is accelerated by uremia, leading to a high prevalence of frailty in patients with advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD) as well as contributing to adverse outcomes in this patient population. Frailty assessment is not routine in patients with CKD; however, a number of validated clinical assessment tools can assist in prognostication. Frailty assessment in nephrology populations supports shared decision-making and advanced communication and should inform key medical transitions. Frailty screening and interventions in CKD or ESKD are a developing research priority with a rapidly expanding literature base.

Outcome of pregnancy in a patient with Gitelman syndrome: a case report.

Gitelman syndrome (GS) is an autosomal-recessive condition characterized by hypokalaemia, hypomagnesaemia and hypocalciuria. Though it affects women of child-bearing age very little information is available about its impact on maternal and fetal outcome. We describe the course of pregnancy in a patient with GS which was characterized by a sixfold increase in potassium and magnesium requirements with inability to achieve normal levels despite intravenous supplementation. There was no adverse impact on the course of pregnancy or fetal outcome. The case highlights the variability in the phenotypic presentation of GS and recommends frequent monitoring of electrolytes with supplementation guided by clinical requirements without aiming to achieve normal blood levels.

Measurement of renal function in kidney donors using serum cystatin C and beta(2)-microglobulin.

BACKGROUND: The usefulness of serum cystatin C and serum beta(2)-microglobulin (B2M) as markers of glomerular filtration rate (GFR) were compared in kidney donors before and after nephrectomy. METHODS: Blood samples were taken from 28 donors (15 women and 13 men) for serum creatinine, urea, cystatin C and B2M estimation a median of 7 days before and 10 days after nephrectomy. RESULTS: Estimated GFR decreased from a median of 86.2 mL/min/1.73 m(2) to 60.3 mL/min/1.73 m(2), a median decrease of 28.6%. Serum creatinine increased by 40% and urea by 30.4%; serum cystatin C increased by 31.2% and serum B2M increased by 65.6%. Using published data on biological variation, critical values were calculated. An increase in serum creatinine above 18 micro mol/L detected the decline in renal function in 26/28 (92.9%) subjects. Increases in serum B2M greater than a critical value of 0.94 mg/L detected 24/28 (85.7%) of these subjects, but the critical value of 0.59 mg/L for cystatin C detected only 8/28 (28.6%). CONCLUSION: Using critical values, serial measurement of serum creatinine was better than serum B2M in detecting reduced renal function. Because of its large intraindividual variation, serial serum cystatin C estimation was very poor in detecting reduced renal function.

First reported case of dialysis-related peritonitis due to Escherichia vulneris.

Escherichia vulneris is a recently identified environmental organism that can colonize humans and animals. To date, very few infections with E. vulneris have been reported. This is the first reported case of peritonitis due to E. vulneris in the setting of peritoneal dialysis.

Switchover to generic cyclosporine in stable renal transplant recipients: a single unit experience.

BACKGROUND: The introduction of the immunosuppressant cyclosporine has significantly improved renal transplant survival. It is an expensive drug and generic alternatives may offer cost advantages. However, generic alternatives must be shown to provide equivalent therapeutic efficacy and safety. This study reports our experience of a switch from the microemulsion formulation of cyclosporine, Neoral (Novartis), to the generic equivalent, Cysporin (Mayne Pharma). METHOD: A two-period, single-sequence, cross-over study was done to compare cyclosporine blood levels and the area under the curve (AUC) of Neoral with Cysporin 2 weeks after a 1:1 dose switch. cyclosporine blood levels were measured at time points 0, 2, 4 and 8 h (C0, C2, C4, C8) after the switch. The cyclosporine AUC at 0-4 h and 0-12 h were calculated using the trapezoidal method. The two formulations were considered to result in equivalent blood levels if the 95% confidence interval (CI) of the ratio of the two levels was within 0.8-1.25. RESULTS AND CONCLUSION: A total of 38 stable renal transplant patients aged 49.79 +/- 11.38 years (mean +/- SD), who were 7.84 +/- 3.97 years postrenal transplantation, were studied. The Neoral dose at the time of the switch was 2.38 +/- 1.21 mg per kg bodyweight. At all measured time points the 95% CI for the cyclosporine drug level ratio was between 0.9 and 1.15. There were no significant adverse events during the period of study. We conclude that the generic formulation of cylosporin, Cysporin, after a 1:1 switch from Neoral results in equivalent blood levels in stable renal transplant recipients. After switchover cyclosporine levels at C0 or C2 can continue to be monitored as per the institution's current monitoring practice.