Trends in Rates of Surgery and Postoperative Mortality Among Patients Receiving Chronic Kidney Replacement Therapy: A Population-based Cohort Study.

OBJECTIVE: To estimate the incidence and postoperative mortality rates of surgery, and variations by age, diabetes, kidney replacement therapy (KRT) modality, and time over a 15-year period. BACKGROUND: Patients with kidney failure receiving chronic KRT (dialysis or kidney transplantation) have increased risks of postoperative mortality and morbidity. Contemporary data on the incidence and types of surgery these patients undergo are lacking. METHODS: This binational population cohort study evaluated all incident and prevalent patients receiving chronic KRT using linked data between Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry and jurisdictional hospital admission datasets between 2000 and 2015. Patients were categorized by their KRT modality (hemodialysis, peritoneal dialysis, home hemodialysis, and kidney transplant) for each calendar year. Incidence rates for overall surgery and subtypes were estimated using Poisson models. Logistic regression was used to estimate 30-day/in-hospital mortality risk. RESULTS: Overall, 46,497 patients over a median (interquartile range) follow-up of 6.3 years (3.5-10.2 years) underwent 81,332 surgeries. The median incidence rate of surgery remained stable over this period with a median of 14.9 surgeries per 100 patient-years. Annual incidence rate was higher in older people and those with diabetes mellitus. Patients receiving hemodialysis had a higher incidence rate of surgery compared with kidney transplant recipients (15.8 vs 10.0 surgeries per 100 patient-years, respectively). Overall adjusted postoperative mortality rates decreased by >70% over the study period, and were lowest in kidney transplant recipients (1.7%, 95% confidence interval, 1.4-2.0). Postoperative mortality following emergency surgery was >3-fold higher than elective surgery (8.4% vs 2.3%, respectively). CONCLUSIONS: Patients receiving chronic KRT have high rates of surgery and morbidity. Further research into strategies to mitigate perioperative risk remain a priority.

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.

Sleep apnea prevalence in chronic kidney disease - association with total body water and symptoms.

BACKGROUND: Sleep apnea is common and associated with poor outcome in severe chronic kidney disease, but validated screening tools are not available. Our objectives were to determine the prevalence of sleep apnea in this population, to assess the validity of screening for sleep apnea using an ApneaLink device and to investigate the relationship of sleep apnea to; symptoms, spirometry and body water. METHODS: Patients with glomerular filtration rate ≤30 mL/min/1.73 m2, whether or not they were receiving haemodialysis, were eligible for enrolment. Participants completed symptom questionnaires, performed an ApneaLink recording and had total body water measured using bioimpedance. This was followed by a multi-channel polysomnography recording which is the gold-standard diagnostic test for sleep apnea. RESULTS: Fifty-seven participants were enrolled and had baseline data collected, of whom only 2 did not have sleep apnea. An apnea hypopnea index ≥30/h was found in 66% of haemodialysis and 54% of non-dialysis participants. A central apnea index ≥5/h was present in 11 patients, with only one dialysis patient having predominantly central sleep apnea. ApneaLink underestimated sleep apnea severity, particularly in the non-dialysis group. Neither total body water corrected for body size, spirometry, subjective sleepiness nor overall symptom scores were associated with sleep apnea severity. CONCLUSIONS: This study demonstrates a very high prevalence of severe sleep apnea in patients with chronic kidney disease. Sleep apnea severity was not associated with quality of life or sleepiness scores and was unrelated to total body water corrected for body size. Routine identification of sleep apnea with polysomnography rather than screening is more appropriate in this group due to the high prevalence.

Allograft adenovirus nephritis.

We present an uncommon case of allograft adenovirus tubulointerstitial nephritis in a 63-year-old male 6 weeks following cadaveric renal transplantation for end-stage renal failure secondary to hypertensive nephrosclerosis. The patient presented with acute onset of fevers, dysuria, haematuria and diarrhoea with acute graft dysfunction. A renal biopsy demonstrated necrotizing tubulointerstitial nephritis with viral cytopathic changes and no evidence of rejection. Adenovirus was identified as the pathogen. Treatment involved the reduction in the patient's usual immunosuppression, intravenous immunoglobulin, piperacillin-tazobactam and ganciclovir. We present the clinical and pathological findings of necrotizing adenoviral nephropathy, highlighting the importance of considering this diagnosis in renal transplant recipients presenting with interstitial nephritis in the setting of a systemic illness.

Spontaneous coronary artery dissection in a woman with polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD), characterized by renal cyst formation, is known to cause such vascular abnormalities as arterial dilatation and dissection. However, spontaneous coronary artery dissection (SCAD) is observed only rarely in patients with ADPKD. We report a patient with ADPKD who developed SCAD and presented with acute myocardial infarction. Her coronary angiography showed a long spiral dissection of the left anterior descending coronary artery. She underwent successful coronary angioplasty with insertion of 3 drug-eluting stents. To the best of our knowledge, this is the first reported case of percutaneous coronary intervention for coronary dissection in a patient with ADPKD. The pathophysiological characteristics of vascular complications in patients with ADPKD are discussed. Polycystins are strongly expressed in human adult vascular smooth muscle cells, and the vascular abnormalities in patients with ADPKD may be related to altered expression of polycystins. Because early recoginition and prompt efforts at mechanical reperfusion, if indicated, are crucial for successful management of SCAD, it would be worthwhile to consider SCAD in the differential diagnoses of acute coronary syndrome in patients with ADPKD.

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.