Trends in kidney transplantation rate across Europe: study from the ERA Registry.

BACKGROUND: The aim of this study was to identify trends in total, deceased donor (DD) and living donor (LD) kidney transplantation (KT) rates in European countries. METHODS: The European Renal Association (ERA) Registry and the Global Observatory on Donation and Transplantation (GODT) databases were used to obtain the number of KTs in individual European countries between 2010 and 2018. General population counts were obtained from Eurostat or the national bureaus of statistics. The KT rate per million population (p.m.p.) and the average annual percentage change (APC) were calculated. RESULTS: The total KT rate in the 40 participating countries increased with 1.9% annually  [95%  confidence  interval  (CI) 1.5, 2.2] from 29.6 p.m.p. in 2010 to 34.7 p.m.p. in 2018, reflecting an increase of 3.4 p.m.p. in the DD-KT rate (from 21.6 p.m.p. to 25.0 p.m.p.; APC 1.9%; 95% CI 1.3, 2.4) and of 1.5 p.m.p. in the LD-KT rate (from 8.1 p.m.p. to 9.6 p.m.p.; APC 1.6%; 95% CI 1.0, 2.3). The trends in KT rate varied widely across European countries. An East-West gradient was observed for DD-KT rate, with Western European countries performing more KTs. In addition, most countries performed fewer LD-KTs. In 2018, Spain had the highest DD-KT rate (64.6 p.m.p.) and Turkey the highest LD-KT rate (37.0 p.m.p.). CONCLUSIONS: The total KT rate increased due to a rise in the KT rate from DDs and to a lesser extent from LDs, with large differences between individual European countries.

Illness perceptions predict mortality in patients with predialysis chronic kidney disease: a prospective observational study.

BACKGROUND: Illness perceptions have been shown to predict a range of psychosocial and clinical outcomes in kidney disease; including quality of life, distress, treatment adherence and even survival in end-stage renal disease patients on dialysis. The aim of this study was to evaluate whether illness perceptions impact mortality in incident predialysis Chronic Kidney Disease (CKD) patients. METHODS: Over the study period between September 2015 and June 2019, a total of 200 participants with predialysis CKD were recruited from the Nephrology Outpatient's clinics at Mater Dei Hospital, Malta. The participants were followed up until June 2019, and the mortality information was collected. Cox proportional hazards models were used to examine the association between illness perceptions, and mortality risk, after adjustment for covariates including distress, kidney function, co-morbidity and psychological distress. RESULTS: Of the 200 cases available for analysis, there were 43 deaths. The mean survival time was 718.55 days (min. 3 days, max. 1297 days). The cumulative survival 1-year post the assessment of the Revised Illness Perceptions Questionnaire (IPQ-R) was 93%. Stronger identity beliefs (HR = 1.199, 95% CI: 1.060-1.357, p = 0.004), perceptions of a chronic timeline (HR = 1.065, 95% CI: 1.003-1.132, p = 0.041), personal control beliefs (HR = 0.845, 95% CI: 0.748-0.955, p = 0.007) and perceptions of control over the treatment (HR = 0.812, 95% CI: 0.725-0.909, p = 0.000) demonstrated a significant association with mortality after controlling covariates. In a subsequent saturated model, perceived identity, chronic timeline and treatment control perceptions remained significant predictors of mortality, together with serum albumin, comorbidities and urea. CONCLUSIONS: CKD patients' perceptions of treatment control, perceptions of a chronic timeline and perceived illness identity predict survival independently of clinical prognostic factors, including kidney function and co-morbidity. Illness perceptions are important and potentially modifiable risk factors in CKD. Further studies are required to test whether the assessment and the implementation of psychological interventions aimed to modify maladaptive illness perceptions influence clinical outcomes in CKD.

The incidence, predictors, and prognosis of acute kidney injury after transcatheter aortic valve implantation
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INTRODUCTION AND AIMS: Transcatheter aortic valve implantation (TAVI) is an alternative procedure for patients with symptomatic aortic stenosis unfit for open heart surgery. Notwithstanding the safer profile, TAVI can still result in serious complications including acute kidney injury (AKI). MATERIALS AND METHODS: We conducted a single-center retrospective study to investigate the incidence of AKI following TAVI, identify any predictors, and assess the impact on patient survival. RESULTS: A total of 104 patients underwent TAVI at a mean age of 76.7 ± 7.2 years. AKI occurred in 35.9% of patients; 26.2% stage 1, 5.8% stage 2, and 3.9% stage 3. These patients had higher incidence of chronic kidney disease (CKD) (37.8 vs. 18.2%; p = 0.035), higher median EuroSCORE-II (4.2, IQR: 5.7 vs. 2.7, IQR: 3.6; p = 0.019), longer hospital stay (6 days, IQR: 7 vs. 5 days, IQR: 3; p = 0.016), and higher all-cause mortality (35.1 vs. 12.1%, p = 0.01) compared to patients without AKI. None of the patient mortality was directly related to the TAVI-AKI event. EuroSCORE-II (OR: 1.19, CI: 1.05 - 1.37, p = 0.009) and CKD (OR: 2.74, CI: 1.10 - 6.82, p = 0.03) were established as independent predictors for AKI. Cumulative survival was lower in patients with AKI (log-rank; χ2 = 6.43, p = 0.011). AKI was established as a hazard for mortality (HR: 2.97, CI: 1.23 - 7.19, p = 0.016). CONCLUSION: More than a third of patients undergoing TAVI developed AKI. These had significantly higher incidence of CKD, higher EuroSCORE-II, higher all-cause mortality, and longer hospital stay. Finally, EuroSCORE-II and CKD were established as independent predictors for AKI and can therefore be used for risk stratification.
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Genotype-phenotype of autosomal dominant polycystic kidney disease in Malta.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of multiple renal cysts causing kidney enlargement and end-stage renal disease (ESRD) in half the patients by 60 years of age. The aim of the study was to determine the genetic aetiology in Maltese patients clinically diagnosed with ADPKD and correlate the clinical features. METHODS: A total of 60 patients over 18 years of age clinically diagnosed with ADPKD were studied using a customized panel of genes that had sufficient evidence of disease diagnosis using next generation sequencing (NGS). The genes studied were PKD1, PKD2, GANAB, DNAJB11, PKHD1 and DZIP1L. Selected variants were confirmed by bidirectional Sanger sequencing with specifically designed primers. Cases where no clinically significant variant was identified by the customized gene panel were then studied by Whole Exome Sequencing (WES). Microsatellite analysis was performed to determine the origin of an identified recurrent variant in the PKD2 gene. Clinical features were studied for statistical correlation with genetic results. RESULTS: Genetic diagnosis was reached in 49 (82%) of cases studied. Pathogenic/likely pathogenic variants PKD1 and PKD2 gene were found in 25 and in 23 cases respectively. The relative proportion of genetically diagnosed PKD1:PKD2 cases was 42:38. A pathogenic variant in the GANAB gene was identified in 1 (2%) case. A potentially significant heterozygous likely pathogenic variant was identified in PKHD1 in 1 (2%) case. Potentially significant variants of uncertain significance were seen in 4 (7%) cases of the study cohort. No variants in DNAJB11 and DZIP1L were observed. Whole exome sequencing (WES) added the diagnostic yield by 10% over the gene panel analysis. Overall no clinically significant variant was detected in 6 (10%) cases of the study population by a customized gene panel and WES. One recurrent variant the PKD2 c.709+1G > A was observed in 19 (32%) cases. Microsatellite analysis showed that all variant cases shared the same haplotype indicating that their families may have originated from a common ancestor and confirmed it to be a founder variant in the Maltese population. The rate of decline in eGFR was steeper and progression to ESRD was earlier in cases with PKD1 variants when compared to cases with PKD2 variants. Cases segregating truncating variants in PKD1 showed a significantly earlier onset of ESRD and this was significantly worse in cases with frameshift variants. Overall extrarenal manifestations were commoner in cases segregating truncating variants in PKD1. CONCLUSIONS: This study helps to show that a customized gene panel is the first-line method of choice for studying patients with ADPKD followed by WES which increased the detection of variants present in the PKD1 pseudogene region. A founder variant in the PKD2 gene was identified in our Maltese cohort with ADPKD. Phenotype of patients with ADPKD is significantly related to the genotype confirming the important role of molecular investigations in the diagnosis and prognosis of polycystic kidney disease. Moreover, the findings also highlight the variability in the clinical phenotype and indicate that other factors including epigenetic and environmental maybe be important determinants in Autosomal Dominant Polycystic Kidney Disease.

COVID-19 vaccine uptake rates, perceptions, and attitudes among dialysis patients: Experience across a national sample.

INTRODUCTION: Dialysis patients are at increased risk of severe COVID-19 infection making vaccination a priority. We explored COVID-19 vaccine uptake and perceptions in our dialysis population, associated COVID-19 infection, and hospitalization rates. METHODS: This is a single-center retrospective study using telephone questionnaires and hospital records to investigate COVID-19 vaccine uptake and attitudes behind vaccination status. RESULTS: A total of 230 patients were interviewed. Vaccine uptake was 97.8% (two doses) and 86.6% (booster dose), with 79.5% vaccinated at Renal Unit. Most (58.5%) cited healthcare worker advice as a contributing factor and 54% sought protection through vaccination. COVID-19 hospitalization was higher in unvaccinated and patients vaccinated with one dose, compared to two doses (63.2% vs. 20%, p = 0.05) and booster dose (63.2% vs. 22.2%, p = 0.02). CONCLUSION: Our dialysis population recognized the importance of COVID-19 vaccination. Intensive patient education and easy access to the COVID-19 vaccine may have facilitated vaccine uptake in these patients.

Bilateral adrenal and pulmonary haemorrhages as an initial presentation of polycythaemia vera.

We report a case of a man in his early 60s presenting with bilateral adrenal and pulmonary haemorrhages as an initial presentation of polycythaemia vera (PV). Symptomatology included severe compressive chest pain radiating to epigastrium, with unremarkable physical findings, parameters and ECG. Blood investigations showed an elevated haemoglobin (174 g/L, reference range (RR): 141-172g/L) and haematocrit (55.7%, RR: 40.4%-50.4%) levels.Cross-sectional imaging excluded aortic dissection, but imaging repeated 48 hours after his admission for acute dyspnoea and worsening abdominal pain showed bilateral alveolar and adrenal haemorrhages. Cortisol level was 27 nmol/L (RR: 145-619 nmol/L). Investigations confirming PV included the presence of a Janus kinase 2 (JAK2V617F) gene mutation, hypercellularity with erythroid hyperplasia on bone marrow microscopy and a low serum erythropoietin (2.6 mIU/mL, RR: 4.3-29.0 mIU/mL). Aspirin, hydroxyurea, venesection and cortisol replacement were initiated to get good treatment outcome.

Illness perceptions predict distress in patients with chronic kidney disease.

BACKGROUND: Patients diagnosed with chronic kidney disease (CKD) report increased distress associated with their clinical diagnosis. Distress in patients with predialysis CKD, has been linked to several adverse events; including increased risk of hospitalisation, early dialysis initiation and even death, suggesting that distress is a matter of great concern during routine care in predialysis CKD. AIMS: The present study aimed to assess the nature of illness perceptions and the level of distress in a CKD cohort diagnosed with different stages of kidney disease. It also aimed to explore the correlates of distress and to create a model for distress and its associated predictors making use of hierarchical regression analysis. METHODS: A sample of 200 patients diagnosed with Chronic Kidney Disease were recruited for this study from the nephrology outpatient clinics of Mater Dei Hospital, Malta. The participants were assessed for their; illness perceptions, treatment beliefs, level of depression and anxiety, coping style, as well as treatment adherence. Routine clinical information was also collected for participants, including a co-morbidity score. RESULTS: A percentage of 33.5% of the participants reported moderate distress, whilst 9.5% reported severe distress. Stronger illness identity, a perception of timeline as being increasingly chronic or cyclical in nature, greater consequences and higher emotional representations were associated with more advanced stages of CKD. In contrast, lower personal and treatment control and poorer illness coherence were associated with more advanced stages of CKD. Results from the hierarchical regression analysis showed that illness perceptions contributed significantly to distress over and above the clinical kidney factors. Being female, having low haemoglobin and specific illness perceptions including; perceptions of greater symptomatology, longer timeline, low personal control and strong emotional representations, as well as resorting to maladaptive coping, were all significantly associated with distress symptoms. Nevertheless, illness perceptions accounted for the greatest variance in distress thus indicating that the contribution of illness perceptions is greater than that made by the other known covariates. CONCLUSION: Illness perceptions hold a principal role in explaining distress in CKD, relative to other traditional covariates. For this reason, illness perceptions should be addressed as a primary modifiable component in the development of distress in CKD.

Chronic kidney disease referral practices among non-nephrology specialists: A single-centre experience.

BACKGROUND: Early referral of CKD patients to nephrology teams (NT) is vital to identify patients most likely to progress, delay decline of excretory function, and provide planned RRT. Unfortunately, many are still being referred late. METHODS: We conducted a retrospective analysis to investigate referral rates, predictors of non-referral, and performed urine investigations in hospitalised CKD patients. RESULTS: Out of 388 patients studied, 5.6%, 11.4%, and 16.4% in CKD3A, 3B, and 4+5, respectively, were referred to an NT upon discharge (CKD3A vs. CKD4+5, p=0.016). For every additional year of age, the odds of being referred decreased by 5% (OR: 0.95, CI: 0.92-0.98, p=0.003). Patients were more likely to be referred to an NT if they were males (OR: 2.31, CI: 1.09-4.90, p=0.029) and having reached CKD 4+5 (OR: 3.99, CI: 1.58-10.10, p=0.003). Only 28.8%, 43.9%, and 50.7% of patients with CKD3A, 3B, and 4+5 were followed up with urine investigations after discharge (p=0.001). CKD stage 3B (OR: 3.54, CI: 1.23-10.19, p=0.019), CKD stage 4+5 (OR: 6.06, CI: 1.69-21.67, p=0.006), DM (OR: 6.28, CI: 2.38-16.58, p<0.0001), and having been referred to a NT (OR: 20.95, CI: 3.54-123.92, p=0.001) were independent predictors for having urine investigations. CONCLUSION: The highest rate of referral was achieved in males, younger age group, and those who have reached CKD stage 4+5. Urine tests remain largely underutilised and only a minority (16.4%) of patients with an eGFR <30mL/min/1.73m(2) were referred to a NT.

Seasonal Variation in the Peritoneal Dialysis-Related Infections: A Single Center Experience in the Mediterranean.

Seasonal variation in the incidence of peritoneal dialysis-related infections (PDRI) has been sparingly investigated, especially in the Mediterranean. Our aim was to explore this association in Malta. All PDRI occurring between Jan-2008 and Dec-2012 were retrospectively studied.A total of 137 patients were followed-up for a median time of 32.5 months (range: 2-81). During this time, 19% never had PDRI, 11.7% transferred permanently to hemodialysis and 6.6% received a kidney transplant. A total of 279 PDRI were identified, equating to 145 catheter-related infections (CRI) and 144 peritonitis episodes (including 10 catheter related peritonitis). A spring peak in the overall gram positive PDRI (0.61 vs. 0.34/patient-year-at-risk, P=0.05), together with a peak in gram negative peritonitis in the warm period (0.13 vs. 0.07/patient-year at risk, P=0.04) was identified. The incidence rate ratios (Confidence Interval) involving the overall gram positive PDRI, gram positive peritonitis, coagulase-negative Streptococci (CoNS) and Streptococci were 1.82 (1.18-2.82, P=0.007), 2.20 (1.16-4.16, P=0.02), 2.65 (1.17-6.02, P=0.02] and 3.18 (1.03-9.98, P=0.04) in spring when compared to winter. No significant difference in the overall PDRI, peritonitis or CRI rates between seasons or warm/cold period was identified.To our knowledge, this is the first study which examines the effect of seasons on the incidence of PDRI in the Mediterranean basin. Findings suggest that spring confers a higher risk for gram positive PDRIs, gram positive peritonitis, CoNS and Streptococcus, whilst the warm period was associated with a peak in the gram negative peritonitis.

Biochemical indices of renal osteodystrophy in dialysis patients on the island of Malta.

OBJECTIVES: Renal osteodystrophy (ROD) has never been studied on the small Mediterranean island of Malta, which has a largely inbred population. The genetic contribution to the pattern of renal osteodystrophy is being increasingly recognized. We were, thus, interested in studying indices of bone turnover in Maltese end stage renal failure patients. MATERIALS AND METHODS: Sixty unselected patients, representing 65% of all patients undergoing dialysis in the island's renal unit, were prospectively investigated over a period of 5 months with respect to symptoms, calcium/phosphate chemistry, intact parathyroid hormone (iPTH) and bone alkaline phosphatase (bAP). Bone histomorphometry, which is the gold standard in the diagnosis of ROD, was not within the reach of our small unit. Biochemical markers may not be as sensitive and specific as bone biopsy for individual patient diagnosis of ROD sub-type but they can give a fairly good indication of the spectrum of bone turnover on a population basis. The optimum combination of biochemical marker cut-offs available from studies in the literature was then employed to estimate bone turnover. RESULTS: The following biochemical picture emerged: 42% had iPTH < 79.7 pg/ml (which cut off has a reported specificity of 93.7% for low turnover bone disease), 45% had iPTH > 100 pg/ml and bAP > 10 ng/ml (which combined cut off has a reported specificity of 100% for high turnover bone disease), while 13% could not be classified (ie had intermediate values). CONCLUSIONS: Based on biochemical data, the pattern of bone turnover seems to be comparable to the European average. Further indepth study using bone histomorphometry is warranted.

Early dialysis in acute kidney injury after cardiac surgery.

Acute kidney injury following cardiac surgery (AKICS) remains a frequent cause of major morbidity and mortality. The aim of this study was to examine the influence of timing of dialysis. A retrospective analysis of 3528 patients undergoing cardiac surgery between April 1995 and July 2006 was performed. In group 1 (April 1995-January 2000) intermittent haemodialysis was resorted to when other supportive measures failed. In group 2 (January 2000-July 2006) intermittent haemodialysis was commenced immediately when oliguria did not respond to fluid replacement or single-dose diuretics. In group 1, 49/1511 (3.2%) patients developed AKICS. Thirty-four patients did not receive dialysis and six patients died (18%). Of the remaining 15 patients who underwent dialysis, 13 died (87%). The overall mortality for group 1 AKICS patients was 19/49 (39%). In group 2, 87/2017 (4.3%) patients developed AKICS. Thirty-one patients did not require dialysis and none died. Of the 56 patients who were dialysed, 14 died (25%). During January 2005-July 2006, mortality following dialysis fell further to 17% (4/24). The overall mortality for group 2 patients developing AKICS was 14/87 (16%). Although the incidence of AKICS increased from 3.2% to 4.2%, earlier dialysis resulted in significantly improved survival (P=0.00001).