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Background Often only chronic kidney disease (CKD) patients with high likelihood of genetic disease are offered genetic testing. Early genetic testing could obviate the need for kidney biopsies, allowing for adequate prognostication and treatment. To test the viability of a 'genetics-first' approach for CKD, we performed genetic testing in a group of kidney transplant recipients aged <50 years, irrespective of cause of transplant. Methods From a cohort of 273 transplant patients, we selected 110 that were in care in the University Medical Center Utrecht, had DNA available and were without clear-cut non-genetic disease. Forty patients had been diagnosed with a genetic disease prior to enrollment; in 70 patients, we performed a whole-exome sequencing-based 379 gene panel analysis. Results Genetic analysis yielded a diagnosis in 51%. Extrapolated to the 273 patient cohort, who did not all fit the inclusion criteria, the diagnostic yield was still 21%. Retrospectively, in 43% of biopsied patients, the kidney biopsy would not have had added diagnostic value if genetic testing had been performed as a first-tier diagnostic. Conclusions The burden of monogenic disease in transplant patients with end-stage kidney disease (ESKD) of any cause prior to the age of 50 years is between 21% and 51%. Early genetic testing can provide a non-invasive diagnostic, impacting prognostication and treatment, and obviating the need for an invasive biopsy. We conclude that in patients who expect to develop ESKD prior to the age of 50 years, genetic testing should be considered as first mode of diagnostics. [ABSTRACT FROM AUTHOR]

Background Dialysis patients have an increased bleeding risk as compared with the general population. However, there is limited information whether bleeding risks are different for patients treated with haemodialysis (HD) or peritoneal dialysis (PD). From a clinical point of view, this information could influence therapy choice. Therefore the aim of this study was to investigate the association between dialysis modality and bleeding risk. Methods Incident dialysis patients from the Netherlands Cooperative Study on the Adequacy of Dialysis were prospectively followed for major bleeding events over 3 years. Hazard ratios with 95% confidence intervals (CIs) were calculated for HD compared with PD using a time-dependent Cox regression analysis, with updates on dialysis modality. Results In total, 1745 patients started dialysis, of whom 1211 (69.4%) received HD and 534 (30.6%) PD. The bleeding rate was 60.8/1000 person-years for HD patients and 34.6/1000 person-years for PD patients. The time-dependent Cox regression analysis showed that after adjustment for age, sex, primary kidney disease, prior bleeding, cardiovascular disease, antiplatelet drug use, vitamin K antagonist use, erythropoietin use, arterial hypertension, residual glomerular filtratin rate, haemoglobin and albumin levels, bleeding risk for HD patients compared with PD increased 1.5-fold (95% CI 1.0–2.2). Conclusions In this large prospective cohort of incident dialysis patients, HD patients had an increased bleeding risk compared with PD patients. In particular, HD patients with a history of prior bleeding had an increased bleeding risk. [ABSTRACT FROM AUTHOR]

Background Bleeding risk scores have been created to identify patients with an increased bleeding risk, which could also be useful in dialysis patients. However, the predictive performances of these bleeding risk scores in dialysis patients are unknown. Therefore, the aim of this study was to validate existing bleeding risk scores in dialysis patients. Methods A cohort of 1745 incident dialysis patients was prospectively followed for 3 years during which bleeding events were registered. We evaluated the discriminative performance of the Hypertension, Abnormal kidney and liver function, Stroke, Bleeding, Labile INR, Elderly and Drugs or alcohol (HASBLED), the AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA), the Hepatic or kidney disease, Ethanol abuse, Malignancy, Older age, Reduced platelet count or Reduced platelet function, Hypertension, Anaemia, Genetic factors, Excessive fall risk and Stroke (HEMORR2HAGES) and the Outcomes Registry for Better Informed Treatment (ORBIT) bleeding risk scores by calculating C-statistics with 95% confidence intervals (CI). In addition, calibration was evaluated by comparing predicted and observed risks. Results Of the 1745 dialysis patients, 183 patients had a bleeding event, corresponding to an incidence rate of 5.23/100 person-years. The HASBLED [C-statistic of 0.58 (95% CI 0.54–0.62)], ATRIA [C-statistic of 0.55 (95% CI 0.51–0.60)], HEMORR2HAGES [C-statistic of 0.56 (95% CI 0.52–0.61)] and ORBIT [C-statistic of 0.56 (95% CI 0.52–0.61)] risk scores had poor discriminative performances in dialysis patients. Furthermore, the calibration analyses showed that patients with a low risk of bleeding according to the HASBLED, ATRIA, HEMORR2HAGES and ORBIT bleeding risk scores had higher incidence rates for bleeding in our cohort than predicted. Conclusions The HASBLED, ATRIA, HEMORR2HAGES and ORBIT bleeding risk scores had poor predictive abilities in dialysis patients. Therefore, these bleeding risk scores may not be useful in this population. [ABSTRACT FROM AUTHOR]

Background. The risk-benefit ratio of vitamin K antagonists for different CHA2DS2-VASc scores in patients with end-stage renal disease treated with dialysis is unknown. The aim of this study was to investigate the association between vitamin K antagonist use and mortality for different CHA2DS2-VASc scores in a cohort of end-stage renal disease patients receiving dialysis treatment. Methods. We prospectively followed 1718 incident dialysis patients. Hazard ratios were calculated for all-cause and causespecific (stroke, bleeding, cardiovascular and other) mortality associated with vitamin K antagonist use. Results. Vitamin K antagonist use as compared with no vitamin K antagonist use was associated with a 1.2-fold [95% confidence interval (95% CI) 1.0-1.5] increased all-cause mortality risk, a 1.5-fold (95% CI 0.6-4.0) increased stroke mortality risk, a 1.3- fold (95% CI 0.4-4.2) increased bleeding mortality risk, a 1.2- fold (95% CI 0.9-1.8) increased cardiovascular mortality risk and a 1.2-fold (95% CI 0.8-1.6) increased other mortality risk after adjustment. Within patients with a CHA2DS2-VASc score ≤1, vitamin K antagonist use was associated with a 2.8-fold (95% CI 1.0-7.8) increased all-cause mortality risk as compared with no vitamin K antagonist use, while vitamin K antagonist use within patients with a CHA2DS2-VASc score ≥2 was not associated with an increasedmortality risk after adjustment. Conclusion. Vitamin K antagonist use was not associated with a protective effect on mortality in the different CHA2DS2-VASc scores in dialysis patients. The lack of knowledge on the indication for vitamin K antagonist use could lead to confounding by indication. [ABSTRACT FROM AUTHOR]

Fluid management has been a vital part of routine clinical care for more than 180 years. The increasing number of available fluids has generated controversy about the optimal choice of resuscitation fluid. In this review, we provide a critical overview of the different fluids available, their composition, the relevant physiology as well as the published evidence on clinical outcomes to guide their use. Commonly used infusion fluids include semisynthetic colloids and crystalloids; the latter comprises both normal saline (NaCl 0.9%) and the more chloride-restricted ‘balanced’ crystalloids. Despite their significantly greater intravascular persistence, semisynthetic colloids have an importantly adverse safety profile and are associated with greater incidence of renal failure and increased mortality; their use should be restricted. To date, evidence for clinical benefits associated with albumin solutions is generally lacking; its merits in specific clinical situations are the subject of further investigation. Infusion of normal saline, with its supraphysiological chloride content, is associated with higher serum chloride concentrations and metabolic acidosis, as well as renal vasoconstriction in animal and human models. Infusion of ‘balanced’ crystalloids is not linked to such changes. Although data on clinical outcomes associated with crystalloid infusion are heterogeneous, advantages of balanced salt solutions might include a lower need of blood products, and lower incidence of renal replacement therapy, hyperkalaemia and postoperative infections. Taken together, a critical appraisal of the data suggests that balanced salt solutions deserve consideration as infusates of first choice. [ABSTRACT FROM AUTHOR]

Background Lithium (Li) is an invaluable drug for the treatment of bipolar disorder. Long-term Li use is associated with renal complications including the formation of uncomplicated renal cysts caused by proliferation and expansion of collecting duct (CD) cells. We report six patients with complicated renal cysts in the context of Li nephropathy. Methods Over a time period of 15 years, we have identified six patients with one or more solid renal tumours in our population of approximately 50 patients with chronic Li nephropathy. In this study we describe the clinical and pathological characteristics of these Li-related tumours. Results All patients were on Li therapy for over 10 years and suffered from varying degrees of Li nephropathy. The tumours were all of CD origin and comprised both oncocytomas and collecting duct carcinomas. The CD carcinomas differed from the very rare “classical” CD cell carcinomas in histological appearance, multifocal presentation and non-aggressive clinical behaviour Conclusions The increased incidence of CD derived tumours and atypical presentation of CD cell carcinomas in patients with chronic Li nephropathy suggests that Li predisposes to the development of these tumours. We hypothesize that prolonged stimulation of CD cell proliferation and expansion by Li not only causes cyst formation, but can eventually induce the formation of adenomas and carcinomas. Increased awareness of a possible relationship between chronic Li therapy and renal neoplasms, will enhance the knowledge on epidemiology, clinical behavior and optimal therapy for the Li-related renal neoplasms. [ABSTRACT FROM PUBLISHER]

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic systemic disorder, which is associated with cyst formation in several organs, renal function decline and a higher prevalence of intracranial aneurysms. We report a 52-year-old, otherwise healthy, man with ADPKD who had asymptomatic, bilateral, multiple cysts in the choroid plexus, which is an extremely rare abnormality. Recent evidence suggests that the polycystin proteins, which are dysfunctional in ADPKD, are found in ciliated choroid plexus cells that are involved with regulation of cerebrospinal fluid homeostasis. We hypothesize therefore that choroid plexus cysts may be part of the ADPKD phenotype, which has not been described before. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Uremia-associated cardiovascular and lung injury" by Z. Yuan and colleagues in the 2012 issue.

The article discusses the case of a 64-year-old female peritoneal dialysis patient who was x-rayed and found to have opacities over her colon and rectosigmoid. Causes of intestinal opacifications are said to be iodine or barium containing contrast media so with telepaque and bismuth-containing drugs. The patient was not using those drugs, however, it was discovered that she was on lanthanum carbonate tablets as a supplement to sevelamer treatment. Lanthanum is known to be trivalent cation with a high affinity with phosphate.