Monogenic causes of chronic kidney disease in adults.

Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD. Affected adults were recruited from 78 families with a positive family history, 16 families with extra-renal features, and 20 families with neither a family history nor extra-renal features. We detected a pathogenic mutation in a known CKD gene in 42 of 114 families (37%). A monogenic cause was identified in 36% of affected families with a positive family history of CKD, 69% of those with extra-renal features, and only 15% of those without a family history or extra-renal features. There was no difference in the rate of genetic diagnosis in individuals with childhood versus adult onset CKD. Among the 42 families in whom a monogenic cause was identified, WES confirmed the clinical diagnosis in 17 (40%), corrected the clinical diagnosis in 9 (22%), and established a diagnosis for the first time in 16 families referred with CKD of unknown etiology (38%). In this multi-centre study of adults with CKD, a molecular genetic diagnosis was established in over one-third of families. In the evolving era of precision medicine, WES may be an important tool to identify the cause of CKD in adults.

Progressive improvement in short-, medium- and long-term graft survival in kidney transplantation patients in Ireland - a retrospective study.

It is often quoted that while short-term graft survival in kidney transplantation has improved in recent years, it has not translated into a commensurate improvement in long-term graft survival. We considered whether this was true of the entire experience of the national kidney transplant program in Ireland. A retrospective analysis of the National Kidney Transplant Service (NKTS) database was undertaken to investigate patient and graft survival for all adult first deceased donor kidney transplant recipients in Ireland, 1971-2015. Three thousand two hundred and sixty recipients were included in this study. Kaplan-Meier methods were used to estimate survival at each time period post transplant for the various eras of transplantation. Uncensored graft survival has improved over the course of the program in Ireland at various time points despite risk factors for graft failure progressively increasing over successive eras. For example the graft survival at 15 years post transplant has increased from 10% in 1971-1975 to 45% by 1996-2000. Ireland has experienced a progressive improvement in long-term graft survival following kidney transplantation. Whether these trends are attributable to biological or nonbiological factors is unclear but likely involves a combination of both.

Metastatic germ cell tumour following renal transplantation.

BACKGROUND: Treatment of germ cell tumours with cisplatin-based chemotherapy results in cure for the majority of patients. There is, however, a small but significant mortality rate, reported to be higher in patients with multiple co-morbidities. CASE REPORT: We report our management of a renal transplant patient with spina bifida, who was diagnosed with stage IIIC, poor-risk, non-seminomatous germ cell carcinoma. A marker-negative partial response, which has been maintained more than 2 years following completion of treatment, was seen following chemotherapy with cisplatin and etoposide. Performance status has been preserved at pre-treatment levels. CONCLUSION: Administration of cisplatin-based chemotherapy is feasible for treatment of renal transplant patients with advanced non-seminomatous germ cell tumours. Treatment strategies require careful planning and monitoring. Dose modifications may be required. This case highlights a favourable outcome in spite of multiple obstacles to ideal management.

Rare case of steroid cell tumour presenting as resistant hypertension in early pregnancy.

A woman 12 weeks and 3 days pregnant was referred to the emergency department with significant hypertension which, despite aggressive medical management, remained uncontrolled. Markedly elevated levels of renin and aldosterone beyond what is typical in early pregnancy were present, which together with the finding of a right ovarian cyst pointed to the possible diagnosis of an extrarenal reninoma.and the decision was made to perform a right-sided oophorectomy at 16 weeks gestation. Histology demonstrated a staining pattern most consistent with a steroid cell tumour leading to the diagnosis of refractory hypertension secondary to an ovarian steroid cell tumour. Post oophorectomy blood biochemistry rapidly returned to normal, and our patient's hypertension slowly resolved allowing for a large reduction in antihypertensive agent requirements and a successful pregnancy outcome.

Evolution of Vascular Access Use among Incident Patients during the First Year on Hemodialysis: A National Cohort Study.

Background: Although the arteriovenous fistula (AVF) confers superior benefits over central venous catheters (CVCs), utilization rates remain low among prevalent patients on hemodialysis (HD). The goal of this study was to determine the evolution of vascular access type in the first year of dialysis and identify factors associated with conversion from CVC to a functioning AVF. Methods: We studiedadult patients (n=610) who began HD between the January 1, 2015 and December 31, 2016 and were treated for at least 90 days, using data from the National Kidney Disease Clinical Patient Management System in the Irish health system. Prevalence of vascular access type was determined at days 90 and 360 after dialysis initiation and at 30-day intervals. Multivariable logistic regression explored factors associated with CVC at day 90, and Cox regression evaluated predictors of conversion from CVC to AVF on day 360. Results: CVC use was present in 77% of incident patients at day 90, with significant variation across HD centers (from 63% to 91%, P<0.001), which persisted after case-mix adjustment. From day 90 to day 360, AVF use increased modestly from 23% to 41%. Conversion from CVC to AVF increased over time, but the likelihood was lower for older patients (for age >77 years versus referent, adjusted hazard ratio [HR], 0.43; 95% CI, 0.19 to 0.96), for patients with a lower BMI (per unit decrease in BMI, HR, 0.95; 95% CI, 0.93 to 0.98), and varied significantly across HD centers (from an HR of 0.25 [95% CI, 0.08 to 0.74] to 2.09 [95% CI, 1.04 to 4.18]). Conclusion: CVCs are the predominant type of vascular access observed during the first year of dialysis, with low conversion rates from CVC to AVF. There is substantial center variation in the Irish health system that is not explained by patient-related factors alone.

Gitelman's syndrome in pregnancy: case report and review of the literature.

Gitelman's syndrome (GS), a rare renal disorder, results in hypokalaemia, hypomagnesaemia, hypocalciuria and a metabolic alkalosis. It is unclear if an alteration in management is necessary or beneficial during pregnancy. A 32-year-old woman with GS was managed in her second pregnancy. Antenatally, the patient required 39 (principally day case) admissions to the hospital for intravenous (IV) therapy and received a cumulative total of 47 l of IV 0.9% saline solution, 47 doses of 20 mmol magnesium chloride and 46 doses of 80 mmol potassium chloride. She delivered a 2940-g female infant in excellent condition by caesarean section. We would suggest that close attention to maternal weight gain during pregnancy is an easily available clinical tool to assess adequacy of fluid and electrolyte repletion in this condition.

Patients referred for arteriovenous fistula construction: a retrospective outcome analysis.

OBJECTIVES: With lower rates of sepsis and re-interventions, arteriovenous fistula (AVF) is the preferred vascular access modality. The aim of this study is to evaluate the outcomes of patients referred for AVF construction at a single center in Cork, Ireland. METHODS: The current study is a single-center retrospective review of all patients who underwent AVF creation between 2015 and 2017. Additionally, the kidney disease clinical patient management system was used to provide statistics on AVF use in Ireland. RESULTS: 39.3% of hemodialysis patients in Ireland use an AVF for vascular access. Regional use ranged from 50 to 20% across Irish hemodialysis centers. At Cork University Hospital, 192 AVFs were created. The population was 69.3% male (n = 133), 30.7% female (n = 59) with a mean (±SEM) age of 58.8 ± 1.03 years. 69.5% of females received a brachiocephalic AVF (BCAVF) while 13.6% had a radiocephalic AVF (RCAVF) constructed. Significance was seen when comparing gender and AVF type (p < 0.001). Fifty-four percent of the fistulae were brachiocephalic (n = 103), 33% were radiocephalic (n = 63), and 4% were brachiobasilic (n = 8). BCAVF patients (62.7 ± 1.2 years) were significantly older than patients receiving a RCAVF (54.5 ± 1.9 years, p < 0.001). A post-operative thrill or continuous flow on Doppler was present in 99% of patients (n = 190) with maturation and complication rates of 82.7% (n = 153) and 5.7% (n = 11) respectively. 69.9% of AVFs were needled for hemodialysis (n = 114). CONCLUSIONS: AVF outcomes at this center are consistent with reported statistics in the literature. Patient age, sex, and diabetic status may influence the use of proximal AVF. AVF creation rates in Ireland are below international reported recommendations.

Do patient-reported measures of symptoms and health status predict mortality in hemodialysis? An assessment of POS-S Renal and EQ-5D.

Introduction Experience with the use of patient-reported outcome measures such as EQ-5D and the symptom module of the Palliative care Outcome Scale-Renal Version (POS-S Renal) as mortality prediction tools in hemodialysis is limited. Methods A prospective survival study of people receiving hemodialysis (N = 362). The EQ-5D and the POS-S Renal were used to assess symptom burden and self-rated health (with a self-rated component). Participants were followed from instrument completion to death or study end. Competing risks survival analysis was used to evaluate associations with time to death, with renal transplant as a competing risk. Findings 32% (N = 116) of participants died over a median (25th-75th centile) of 2.6 (1.41-3.38) years. Factors most notably associated with mortality adjusted hazard ratio (95%CI) included: lower EQ VAS score 2.7 (1.4, 5.2) P = 0.004 (lowest tertile), higher POS-S Renal score 2.4 (1.3, 4.3) P = 0.004 (highest tertile), and lower EQ-5D score 2.6 (1.3, 5.3) P = 0.01 (lowest tertile) as well as the presence of: "problems with mobility?" 2 (1.1, 3.3) P = 0.01, or "problems with usual activities?" 2.1 (1.4, 3.3), P < 0.001. After age adjustment area under the receiver operating curves (AUC) (95%CI) for mortality were: 0.71 (0.62, 0.79) for EQ VAS score, 0.71 (0.63, 0.80) for POS-S Renal-S Renal score, and 0.76 (0.68, 0.84) for EQ-5D score. AUC 95%CI was highest for our fourth model at 0.79 (0.72, 0.86) comprised of individual elements from both instruments and established risk factors. Discussion EQ VAS scores and predictive models based on combinations of elements from the POS-S Renal and EQ-5D instruments may aid in mortality discrimination and possibly in the delivery of supportive care services.

Understanding What Influences the Health-Related Quality of Life of Hemodialysis Patients: A Collaborative Study in England and Ireland.

CONTEXT: The international cohort of hemodialysis patients is aging and increasing in number. Nephrologists have a therapeutic relationship with their patients that may span decades. Often overlooked components of chronic disease management include symptom control and assessment of health-related quality of life (HRQoL). OBJECTIVES: This study describes the symptom profile of a large cohort of patients with end-stage renal disease on hemodialysis in England and Ireland and evaluates how symptom burden and other factors influence quality-of-life scores. METHODS: A prospective cross-sectional observational study of hemodialysis patients was conducted in Ireland and England during 2011 and 2012. Two validated clinical tools were used to determine HRQoL and symptom burden. Demographic and clinical data were examined, and regression analysis was used to determine associations with HRQoL scores. RESULTS: A total of 893 patients on hemodialysis (mean [SD] age 64 [16] years) had a high symptom burden and poor HRQoL compared with population norms. Specifically, 64% of patients reported pain (95% confidence interval 61%-67%) and 79% reported weakness (95% confidence interval 75%-81%). A total of 43 percent of patients reported between six and 10 symptoms in the week preceding the survey. HRQoL was significantly and independently associated with poor mobility and pain and remained significant after adjusting for variations in clinical characteristics. Being listed on a transplant wait-list register was positively associated with HRQoL. CONCLUSION: These findings illustrate the high symptom burden and poor HRQoL of the hemodialysis population. Emphasis during clinical reviews on pain assessment and on assessing mobility plus interventions, such as pain management and physiotherapy/occupational therapy, are practical ways for renal teams to help improve patients' quality of life.

Management of comorbidities in older patients with cystic fibrosis.

Several key advances have been made in the treatment and management of people with cystic fibrosis in the past two decades. Substantial improvements in survival have resulted from the introduction of key drugs, coordinated care packages, improved nutritional support, and the intensive use of antibiotics. The age profile of people with cystic fibrosis has changed greatly during this time-some countries now have more adult than paediatric patients with the disease. With their increasing age and more advanced lung disease, several important sequelae (both pulmonary and extrapulmonary) occur in these adult patients including pulmonary disease, cystic fibrosis-related diabetes, renal disease, metabolic bone disease, cancers, drug allergies and toxic effects, and complications associated with lung transplantation.

Haemodialysis-induced syncope due to Chiari II malformation.

Spina bifida (SB) is associated with chronic kidney disease as a result of vesicoureteric reflux. A proportion of patients progress to end-stage kidney disease (ESKD). Haemodialysis (HD) is probably the most common modality in ESKD, as intra-abdominal malformations and previous surgery can make peritoneal dialysis more challenging. The Chiari malformations also frequently occur in these patients. We report a case of recurrent syncope induced by HD in a patient with SB and the Chiari II malformation. Sparse data exist on the complications of HD in this patient population and on the approach to the management of dialysis-induced syncope in these individuals.

A CF patient with progressive proteinuric renal disease: a CF-specific nodular glomerulosclerosis?

Cystic fibrosis (CF) is a multisystemic disease but without a classical disease-specific renal phenotype. A 32-year-old male patient with CF (ΔF508/ΔF508) presented with a nephrotic syndrome. Renal biopsy revealed nodular glomerulosclerosis (NGS) occurring in the absence of diabetes mellitus, amyloidosis and any other known common cause of NGS. He had a progressive decline in estimated glomerular filtration rate (eGFR) to chronic kidney disease stage V (eGFR <15 mL/min/1.73 m(2)) over a 3-year period despite optimal medical management. This is the fourth reported case of NGS in a patient with CF without diabetes and is the first to originate from a European country. This case supports the concept of a CF-related NGS.