Survival, cumulative hospital days and infectious complications in urgent-start PD compared with urgent-start HD.

BACKGROUND: Urgent-start peritoneal dialysis (PD) carries a similar efficacy and safety profile compared to urgent-start haemodialysis (HD) but is only sparsely applied due to resource issues and concerns of complication risks. Furthermore, few data exist on adverse outcomes associated with central venous catheter (CVC) insertions in urgent-start HD patients. Thus, we sought to compare patient and dialysis-related outcomes in patients undergoing urgent-start PD or HD. METHODS: All patients initiating urgent-start PD in a tertiary research hospital in 2005-2018 were included in this retrospective, single-centre, comparative study and matched with urgent-start HD patients of similar age and chronic kidney disease aetiology. All urgent-start PDs were initiated within 72 h after catheter insertion, and urgent-start HDs were performed via a CVC. All analyses were performed at 3 months and at 1 year of follow-up, respectively. RESULTS: Thirty-three patients who commenced urgent-start PD and 58 matched urgent-start HD control patients were included. Altogether, 26 patients (29%; PD: 36%, HD 24%) died within the 1-year follow-up, and patient survival was similar at 3 months (hazard ratio (HR): 1.15, 95% confidence interval (CI): 0.35-3.81, p = 0.82) and at 1 year of follow-up (HR: 0.64, 95% CI: 0.30-1.39, p = 0.26) between the study groups. There were no differences in the total kidney replacement therapy (KRT)-related infection rate (p = 0.66) or cumulative first-year hospital care days (p = 0.43) between the treatment groups. Altogether, 139 CVCs were inserted during the 1-year follow-up. The number of CVCs per patient was associated with the emergence of blood culture-positive bacteraemia and increased cumulative first-year hospital care days. CONCLUSIONS: Patient survival, cumulative first-year hospital care days and total KRT-related infection rate at 3 months and 1-year follow-up are similar between urgent-start PD and urgent-start HD patients. Furthermore, CVC insertion rate is associated with incident blood culture-positive bacteraemia and increased cumulative first-year hospital care days.

The Relationship of Kidney Function, Cardiovascular Morbidity, and All-Cause Mortality: a Prospective Primary Care Cohort Study.

BACKGROUND: Lower-than-normal estimated glomerular filtration rate (eGFR) is associated with the risk for all-cause mortality and adverse cardiovascular events. In this regard, the role of higher-than-normal eGFR is still controversial. OBJECTIVE: Investigate long-term clinical consequences across the levels of eGFR calculated by the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation among apparently healthy cardiovascular risk subjects. DESIGN: Prospective study. PARTICIPANTS: Participants (n=1747) of a population-based screening and intervention program for cardiovascular risk factors in Finland during the years 2005-2007. MAIN MEASURES: Cardiovascular morbidity and all-cause mortality. KEY RESULTS: Over the 14-year follow-up, subjects with eGFR ≥105 ml/min/1.73 m2 (n=97) had an increased risk for all-cause mortality [HR 2.15 (95% CI: 1.24-3.73)], incident peripheral artery disease [HR 2.62 (95% CI: 1.00-6.94)], and atrial fibrillation/flutter [HR 2.10 (95% CI: 1.21-3.65)] when compared to eGFR category 90-104 ml/min after adjustment for cardiovascular and lifestyle-related risk factors. The eGFR category ≥105 ml/min was also associated with a two-fold increased mortality rate compared to the Finnish general population. CONCLUSIONS: Renal hyperfiltration defined as eGFR ≥105 ml/min/1.73 m2 is a frequent and important finding in patients commonly treated in primary care. These patients should be followed closely for timely interventions, such as strict BP and blood glucose regulation.

Celiac disease antibody levels reflect duodenal mucosal damage but not clinical symptoms.

OBJECTIVES: This study aimed to investigate, in a real-world population, whether the histological and clinical phenotype differ at baseline and during follow-up in patients with high and low CD (celiac disease) antibody titers. MATERIALS AND METHODS: The study cohort consisted of 96 consecutive patients diagnosed to have CD during the years 2010-2018. The clinical parameters, symptoms and laboratory results were registered and histomorphometry was analyzed from the available duodenal biopsies taken during the primary and follow-up esophageal-gastricduodenoscopies. Patients having immunoglobulin A transglutaminase antibody (tTG-ab) levels above 70 U/mL were classified as high titer patients. RESULTS: Measured by the villous-crypt ratio, the duodenal mucosa was more severely damaged in the high tTG-ab group than in the low tTG-group at baseline (n = 70, 0.61 ± 0.63 vs. 1.02 ± 0.87, p = .003) and during the follow-up when the patients were on gluten-free diet (n = 27, 1.80 ± 0.72 vs. 2.35 ± 0.64, p = .041). Interestingly, the high tTG-ab group members had fewer gastrointestinal symptoms at baseline than those in the low tTG-ab group (43% vs. 68%, p = .013) but lower vitamin D levels (68 ± 34 nmol/L vs. 88 ± 29 nmol/L, p = .034) and more often microcytosis (28% vs. 10%, p = .040). During the follow-up, these differences were no longer detected. CONCLUSIONS: At baseline, CD patients with high tTG-ab have more severe duodenum injury and signs of malabsorption but fewer symptoms. After gluten-free diet has been initiated, the mucosal healing in the high tTG-ab group is prolonged, but symptoms and signs of malabsorption recover equally in both groups.

Living donor kidney transplantation.

While the majority of kidney transplantations in Finland have been traditionally performed from deceased donors, the frequency of living donors should be increased. Kidney donation is a safe procedure for a carefully examined donor, and for the recipient living donation enables elective surgery and preemptive transplantation. Potential risks for the donor must be minimized, but according to current recommendations, mild hypertension or obesity are not absolute contraindications for donation. Guidelines for donor selection and examination have been updated to simplify the process for all parties. Legislation in Finland requires changes to optimize the use of all potential living donors.

Potentially pathogenic circulating autoantibodies to cardiac troponin are present in hemodialysis patients.

INTRODUCTION: Repetitive dialysis-induced cardiac injury is associated with elevated troponin levels, inflammation, and longitudinal reduction in cardiac function. Pathogenic autoantibodies to cardiac troponins (cTnAAb) produce inflammatory cardiomyopathy in murine models. This study aimed to explore the possibility that analogous autoimmune processes might occur in hemodialysis (HD) patients, by initially investigating cTnAAb prevalence, and exploring potential links with HD-induced myocardial stunning. METHODS: In 130 prevalent HD patients from two centers (Derby, UK; Turku, Finland), cTnAAb (immunoassay) and cardiac troponins were quantified. Sixty-four patients underwent serial echocardiography to assess myocardial stunning. FINDINGS: cTnAAb were present in 7% of patients. Dual positivity to cTnAAb and elevated cTn occurred in 3% and 6% for cTnI and cTnT, respectively. Patients with cTnAAb had significantly longer dialysis vintage (82 vs. 30 months, P = 0.024), higher cTnT (0.1 vs. 0.05 pg/mL, P = 0.04), cTnI (0.02 vs. 0.01 pg/mL, P = 0.029), and free PAPP-A (6.4 vs. 3.3 mIU/L, P = 0.038). DISCUSSION: This is the first description of cTnAAb in HD patients, which raises the possibility that longitudinal exposure to repetitive HD-induced cardiac injury may lead to further autoimmune-based myocardial insult.

Elevated serum free pregnancy-associated plasma protein-A independently predicts mortality in haemodialysis patients but is not associated with recurrent haemodialysis-induced ischaemic myocardial injury.

BACKGROUND/AIMS: Pregnancy-associated plasma protein-A (PAPP-A) is a putative marker of atheroma instability and ischaemic myocardial stress prior to necrosis. Total PAPP-A (tPAPP-A) levels in acute coronary syndromes predict adverse outcomes. However, free PAPP-A (fPAPP-A) predominates in the circulation. Ischaemic haemodialysis (HD)-induced cardiac injury (myocardial stunning) is common and is associated with markers of myocardial necrosis, inflammation, cardiovascular events and mortality. Coronary plaque instability in pathophysiology of HD-induced myocardial stunning has not been studied. We aimed to investigate the relationship of fPAPP-A with stunning and mortality. METHODS: 130 prevalent patients from two HD centres (Finland and UK) were studied. Pre-HD free, complexed and total PAPP-A were measured by immunoassay. A subset of 62 patients underwent echocardiography to assess HD-induced myocardial stunning. The mean duration of follow-up was 407 ± 98 days. RESULTS: fPAPP-A was elevated (median: 3.45 mIU/l) and correlated with dialysis vintage (r = 0.391, p < 0.001), cardiac troponin T (cTnT; r = 0.29, p = 0.001) and cardiac troponin I (cTnI; r = 0.22, p = 0.01). PAPP-A was not related to stunning. Dialysis vintage and cTnT independently predicted Ln fPAPP-A (model R = 0.463). fPAPP-A, cTnT and age independently predicted death (Nagelkerke R(2) = 0.362). CONCLUSIONS: fPAPP-A, a novel predictor of HD-related mortality, demonstrates better prognostic power than tPAPP-A. Coronary plaque instability may contribute to sub-lethal myocardial injury, but may not be critical in pathogenesis of HD-induced ischaemic cardiac injury.

Thromboembolism as a cause of renal artery occlusion and acute kidney injury: the recovery of kidney function after two weeks.

Thromboembolic occlusion is a rare cause of acute kidney injury (AKI). It may lead to permanent loss of renal function. Our patient, who had dilated cardiomyopathy and prosthetic aortic valve, presented with AKI due to thromboembolic arterial occlusion of a solitary functioning kidney. After 2 weeks delay, local intra-arterial thrombolytic treatment with recombinant tissue plasminogen activator was performed without sufficient effect. However, a subsequent percutaneous transluminal angioplasty with stenting was successful. Diuresis began immediately, and renal function was fully recovered after 2 weeks. Although there had been no evident arterial circulation in the kidney, we think that minor flow through subtotal occlusion of the main renal artery made the hibernation of kidney tissue possible and contributed to the recovery. Thus, even after prolonged ischemia, revascularization can be useful.

[Kidney transplantation from a living donor: criteria for donor and recipient]. / Munuaissiirto elävältä luovuttajalta: luovuttajan ja vastaanottajan kriteerit.

The annual number of kidney transplantations in Finland is 150 to 200. Successful kidney transplantation improves the patient's quality of life and prognosis and is cost-effective as compared with dialytic therapy. Only a few per cent of transplantations are made from a living donor. Waiting times for kidney transplantations have become longer in the last few years. Whereas attempts should be made to better identify potential brain-dead organ donors in order to increase kidney transplantations, transplantations from living donors could also reduce the disproportion between the availability and the need of organs.

The effect of revascularization of renal artery stenosis on renal perfusion in patients with atherosclerotic renovascular disease.

BACKGROUND: Only a small fraction of patients with atherosclerotic renovascular disease (ARVD) treated with revascularization have improved renal function after the procedure. It has been suggested that this may be due to effects of renal microvascular disease. Our aim was to measure the effect of renal artery stenosis (RAS) revascularization on renal perfusion in patients with renovascular disease. METHODS: Seventeen renovascular disease patients were treated by dilatation of unilateral (N = 8) or bilateral (N = 9) RAS (N = 23 kidneys), mainly because of uncontrolled or refractory hypertension. The patients were studied before and after (103 ± 29 days) the procedure. Renal perfusion was measured using quantitative positron emission tomography (PET) perfusion imaging. RESULTS: Although renal perfusion correlated inversely with the degree of RAS in patients with renovascular disease, it did not change after revascularization. CONCLUSIONS: Our data support the notion of former clinical trials that angiographic severity of RAS does not determine the response to revascularization. Quantitative PET perfusion imaging is a promising tool to noninvasively measure renal perfusion for the assessment of physiological impact of RAS.

Cystatin C as a predictor of all-cause mortality and myocardial infarction in patients with non-ST-elevation acute coronary syndrome.

OBJECTIVES: To investigate the predictive value of cystatin C among patients diagnosed with non-ST-elevation acute coronary syndrome (nSTE-ACS). DESIGN AND METHODS: Admission serum samples from 245 nSTE-ACS patients were measured with a novel cystatin C immunoassay based on a dry-reagent, double monoclonal design. Creatinine concentrations, estimated glomerular filtration rates (eGFR) and one-year follow-up data were available for these patients. RESULTS: During the follow-up period, 34 (14%) of patients had myocardial infarction (MI) and 25 (11%) died. Increased serum cystatin C was an independent predictor of all-cause mortality and combined events (all-cause mortality and MI) after adjustment to non-biomarker baseline factors, hazard ratio (HR) 2.19 (per increase of 1 tertile; 95% Cl 1.28-3.78, p=0.0046) and 1.75 (1.22-2.51, p=0.0024), respectively. Corresponding values for eGFR were 2.56 (1.43-4.59, p=0.0016) and 1.76 (1.23-2.53, p=0.0022), respectively. Creatinine was not an independent predictor of endpoints (p>0.05). CONCLUSIONS: Cystatin C was associated with an increased risk of death and combined events in patients with nSTE-ACS.

[Sodium thiosulfate--new hope for the treatment of calciphylaxis]. / Natriumtiosulfaatti --toivoa kalsifylaksian hoitoon.

Calciphylaxis is a rare disease primarily affecting patients dependent on dialysis. It is characterised by small vessel media calcification leading to cutaneous ischemia and necrosis. The mortality rate is high with infection and sepsis being the most common causes of death. Calcium salts, vitamin D and high levels of serum calcium and phosphorus increase the risk of calciphylaxis. Current therapies including restoration of mineral homeostasis, wound care and pain control, are not entirely effective. Sodium thiosulfate, by dissolving calcium deposits, is a novel therapeutic choice for calciphylaxis. It has proved successful also in cases refractory to conventional treatment.

Studies on the effects of heparin products on pregnancy-associated plasma protein A.

BACKGROUND: Intravenous low molecular weight (LMWH) and unfractionated heparin (UFH) increase the circulating concentrations of pregnancy-associated plasma protein A (PAPP-A), a novel cardiac risk marker, in haemodialysis and coronary angiography patients. METHODS: To further investigate the mechanisms of heparin effects, free PAPP-A was analysed in serial serum samples collected during haemodialysis (intravenous LMWH), carotid endarterectomy or abdominal aortic aneurysm surgery (intravenous UFH), treatment at intensive care unit (subcutaneous LMWH), and coronary angiography (intravenous bivalirudin). PAPP-A was extracted from plaque tissue samples of endarterectomy and aneurysm patients. The interaction between heparin products and free PAPP-A was studied with gel filtration. RESULTS: After intravenous UFH and LMWH free PAPP-A increased significantly but bivalirudin had no effect. After LMWH bolus in haemodialysis patients 85% of free PAPP-A was cleared with a half-life of 13.1 min and the rest with a half-life of 96.6 min. Subcutaneous LMWH led to lower and slower free PAPP-A elevation. PAPP-A extracted from plaque tissues was in free form and extraction was strongly enhanced by LMWH. Heparin products increased the molecular size of free PAPP-A. CONCLUSIONS: The heparin-induced PAPP-A elevation is seen in various patients and should be taken into account when PAPP-A is studied as a biomarker.

Increased basal myocardial perfusion in patients with chronic kidney disease without symptomatic coronary artery disease.

BACKGROUND: Even minor renal dysfunction is a powerful cardiovascular risk factor. The abnormalities in coronary and peripheral artery function in different stages of chronic kidney disease (CKD) remain poorly understood. Our aim was to test by a positron emission tomography (PET)-based method whether microvascular dysfunction, an early marker of coronary dysfunction, exists already in early stages of CKD. METHODS: Myocardial blood flow was measured at baseline and during dipyridamole-induced hyperaemia by PET. Peripheral artery endothelial function was examined by measuring flow-mediated dilatation (FMD) of the brachial artery at rest and during reactive hyperaemia. Twenty-two patients with moderate to severe kidney failure and 10 healthy controls were investigated. Diabetic patients were excluded. Baseline characteristics were similar between the groups with the exception of antihypertensive medication in all CKD patients. RESULTS: The basal myocardial perfusion was statistically significantly higher in CKD patients than observed values in similarly aged controls. There was a statistically significant negative correlation between the baseline myocardial perfusion and the estimated glomerular filtration rate. Coronary flow reserve was comparable to healthy controls in all patients. FMD was significantly reduced in all patients with CKD regardless of the stage of kidney failure. CONCLUSIONS: Coronary flow reserve was normal although baseline myocardial blood flow was increased in all CKD patients as compared to healthy controls. Peripheral endothelial dysfunction was detected in all patients. Our findings suggest that coronary perfusion and peripheral vascular function are disturbed by different mechanisms in patients with CKD.

Intravenous administration of low molecular weight and unfractionated heparin elicits a rapid increase in serum pregnancy-associated plasma protein A.

BACKGROUND: Pregnancy-associated plasma protein A (PAPP-A) has been suggested as a useful diagnostic and prognostic marker in acute coronary syndromes. Because low molecular weight heparin (LMWH) and unfractionated heparin (UFH) are commonly used in these cases, we analyzed the effects of intravenous administration of these heparins on serum PAPP-A concentrations. METHODS: Serum concentrations of total and free PAPP-A were analyzed in 14 patients on chronic hemodialysis and in 10 coronary angiography patients. Ten of the dialysis patients received standard LMWH anticoagulation at the start of dialysis, and 4 were treated with a heparin-free method. Two of the patients on heparin-free hemodialysis received a reduced LMWH bolus 2 h after the start of dialysis. All angiography patients received UFH at the start of the procedure, and 1 patient received 2 extra boluses of UFH. Serum PAPP-A concentrations were analyzed before and during the dialysis session and during the coronary angiography examination. RESULTS: A rapid increase in total PAPP-A (median, 25-fold) was seen in all patients within 5 min of administration for both LMWH and UFH boluses. This response was due to an increase in free PAPP-A in the serum. PAPP-A did not increase significantly in the patients who underwent heparin-free hemodialysis. Repeated heparin boluses induced a new PAPP-A release. In vitro addition of heparins to samples of whole blood did not increase PAPP-A concentrations. CONCLUSIONS: Intravenous administration of heparin induces an intense and rapid increase in free PAPP-A in the serum. We recommend that this effect be considered when PAPP-A is assessed as a biomarker in acute coronary syndromes.

Parametric renal blood flow imaging using [15O]H2O and PET.

PURPOSE: The quantitative assessment of renal blood flow (RBF) may help to understand the physiological basis of kidney function and allow an evaluation of pathophysiological events leading to vascular damage, such as renal arterial stenosis and chronic allograft nephropathy. The RBF may be quantified using PET with H(2)(15)O, although RBF studies that have been performed without theoretical evaluation have assumed the partition coefficient of water (p, ml/g) to be uniform over the whole region of renal tissue, and/or radioactivity from the vascular space (V(A). ml/ml) to be negligible. The aim of this study was to develop a method for calculating parametric images of RBF (K(1), k(2)) as well as V(A) without fixing the partition coefficient by the basis function method (BFM). METHODS: The feasibility was tested in healthy subjects. A simulation study was performed to evaluate error sensitivities for possible error sources. RESULTS: The experimental study showed that the quantitative accuracy of the present method was consistent with nonlinear least-squares fitting, i.e. K(1,BFM)=0.93K(1,NLF)-0.11 ml/min/g (r=0.80, p<0.001), k(2,BFM)=0.96k(2,NLF)-0.13 ml/min/g (r=0.77, p<0.001), and V(A,BFM)=0.92V(A,NLF)-0.00 ml/ml (r=0.97, p<0.001). Values of the Akaike information criterion from this fitting were the smallest for all subjects except two. The quality of parametric images obtained was acceptable. CONCLUSION: The simulation study suggested that delay and dispersion time constants should be estimated within an accuracy of 2 s. V(A) and p cannot be neglected or fixed, and reliable measurement of even relative RBF values requires that V(A) is fitted. This study showed the feasibility of measurement of RBF using PET with H(2)(15)O.

Acetazolamide may provoke cyclosporine toxicity-a case report.

We describe a 58-year-old female renal transplantant recipient with standard cyclosporine-based immunosuppression who developed a potentially toxic cyclosporine concentration of 265 ng/ml after having started acetazolamide for severe glaucoma. The mechanism explaining the interaction between acetazolamide and cyclosporine remains unknown, but the concomitant use of these agents is not uncommon. The follow-up of cyclosporine concentrations is necessary, and the reduction of the cyclosporine dose is likely to be needed when patients taking cyclosporine are started with acetazolamide.

Comparison of calcium phosphate product values using measurement of plasma total calcium and serum ionized calcium.

Calcium phosphate product (Ca x Pi) is a clinically relevant tool to estimate the cardiovascular risk of patients with renal failure. In reports, mostly total serum calcium has been used. As measurement of serum ionized calcium has some benefits and is being used increasingly, we estimated the respective levels of calcium phosphate product using both total (t-Ca x Pi) and ionized calcium (ion-Ca x Pi). Fifty-eight healthy individuals and 180 hemodialysis (HD) patients from 2 centers were studied. Diagnostic accuracies for corresponding values of the t-Ca x Pi and ion-Ca x Pi were calculated using a GraphROC program. Of HD patients, 64% had t-Ca x Pi <4.4 mmol(2)/L(2) regarded as a desirable goal, and 10% had values over 5.6 mmol(2)/L(2) associated with a high cardiovascular risk. Based on GraphROC analysis, t-Ca x Pi of 4.4 mmol(2)/L(2) corresponded to a value of 2.2 mmol(2)/L(2) of ion-Ca x Pi and, respectively, t-Ca x Pi of 5.6 mmol(2)/L(2) corresponded 2.8 mmol(2)/L(2) of ion-Ca x Pi. Owing to the good agreement between the results in the 2 centers, these values for risk levels can be used in both centers. When measurement of ionized calcium is used, Ca x Pi values of 2.2 and 2.8 mmol(2)/L(2) can be used instead of generally used values of 4.4 and 5.6 mmol(2)/L(2) with total calcium.

Identification of a genomic subgroup of BK polyomavirus spread in European populations.

BK polyomavirus (BKV) is highly prevalent in the human population, infecting children without obvious symptoms and persisting in the kidney in a latent state. In immunosuppressed patients, BKV is reactivated and excreted in urine. BKV isolates worldwide are classified into four serologically distinct subtypes, I-IV, with subtype I being the most frequently detected. Furthermore, subtype I is subdivided into subgroups based on genomic variations. In this study, the distribution patterns of the subtypes and subgroups of BKV were compared among four patient populations with various immunosuppressive states and of various ethnic backgrounds: (A) Finnish renal-transplant recipients; (B) Irish/English haematopoietic stem-cell transplant recipients with and without haemorrhagic cystitis; (C) Japanese renal-transplant recipients; and (D) Japanese bone-marrow transplant recipients. The typing sequences (287 bp) of BKV in population A were determined in this study; those in populations B-D have been reported previously. These sequences were subjected to phylogenetic and single nucleotide polymorphism analyses. Based on the results of these analyses, the BKV isolates in the four patient populations were classified into subtypes and subgroups. The incidence of subtype IV varied significantly among patient populations. Furthermore, the incidence of subgroup Ib-2 within subtype I was high in populations A and B, whereas that of Ic was high in populations C and D (P<0.01). These results suggest that subgroup Ib-2 is widespread among Europeans, whereas Ic is unique to north-east Asians. Furthermore, a phylogenetic analysis based on complete BKV DNA sequences supported the hypothesis that there is geographical separation of European and Asian BKV strains.

Three-year analysis of microbial aetiology and antimicrobial susceptibilities of PD peritonitis.

The first-line antibiotic treatment of peritoneal dialysis (PD) peritonitis has to cover the most common causative microorganisms. Our aim was to analyse antimicrobial sensitivities of different empirical protocols for initial therapy of PD peritonitis. We analysed the aetiological microorganisms of PD peritonitis and their antimicrobial sensitivities during a 36-month period. Clinical characteristics of the cases were recorded. Altogether 86 PD peritonitides were diagnosed during the study period. In 58 cases, microbial cultures were positive with 72 different causative agents. 28 cases (33%) were culture-negative. Over-representation of icodextrin users was noted among the culture-negative cases. Staphylococcus aureus was the most frequent causative agent, often leading to severe course of illness. Of antimicrobial protocols for initial treatment of peritonitis tested in vitro, the combination of a first-generation cephalosporin and an aminoglycoside was superior to the combination of a first-generation cephalosporin and ceftazidime as well as to fluoroquinolone monotherapy but similar to the combination of vancomycin and ceftazidime. Based on antimicrobial sensitivities we continue using an aminoglycoside in the empirical treatment of PD peritonitis. In the present material, users of icodextrin PD fluid were over-represented among patients with culture-negative peritonitis.