Kidney failure amongst Irish Travellers.

BACKGROUND: The occurrence of Kidney Failure with Replacement Therapy (KFRT) amongst Irish Travellers has not been well described. This study aims to determine the burden of KFRT amongst the Irish Traveller population and identify determinants of health amongst this cohort which may differ from the general population in Ireland. METHODS: This retrospective cohort study included self-identifying Irish Travellers with KFRT registered in the National Kidney Disease Clinical Patient Management System between 1995 and 2022. KFRT was defined as Chronic Kidney Disease stage 5 (CKD G5) treated by dialysis or CKD G1-G5 after transplantation. The primary outcome measure was the prevalence of KFRT in Irish Travellers. Secondary exploratory outcomes included age at diagnosis, family history, biopsy diagnosis, kidney replacement therapy (KRT) modality, time to initiation of KRT, primary vascular access used, and time to receive a kidney transplant. RESULTS: Four of six Irish hospital groups participated in the study. A total of 38 patients were identified as Irish Travellers with KFRT, with a crude prevalence rate of KFRT of 0.12% (CI 0.084-0.161, 95%) or 11.9 per 10,000 Irish Travellers. The mean age for diagnosis of kidney disease was 43 (SD, 20.8) and at commencement of KRT was 45 (SD, 20.9) years. A biopsy-proven diagnosis was provided in 24%. Twenty-two per cent was diagnosed with polycystic kidney disease or congenital anomalies of the kidney and urinary tract. The predominant modality for KRT was haemodialysis (89%), with central venous catheters being the most common initial vascular access (79%). Kidney transplants occurred in 45% of those studied, with a mean waiting time of 1.96 (SD, 1.6) years. CONCLUSIONS: The Irish Traveller community have similar prevalence of KFRT when compared to the national prevalence, with a short time interval from diagnosis to commencement of KRT. They are less likely to avail of home therapies but have comparable wait times to the national waiting time to receive a kidney transplant.

The utility of a genetic kidney disease clinic employing a broad range of genomic testing platforms: experience of the Irish Kidney Gene Project.

BACKGROUND AND AIMS: Genetic testing presents a unique opportunity for diagnosis and management of genetic kidney diseases (GKD). Here, we describe the clinical utility and valuable impact of a specialized GKD clinic, which uses a variety of genomic sequencing strategies. METHODS: In this prospective cohort study, we undertook genetic testing in adults with suspected GKD according to prespecified criteria. Over 7 years, patients were referred from tertiary centres across Ireland to an academic medical centre as part of the Irish Kidney Gene Project. RESULTS: Among 677 patients, the mean age was of 37.2 ± 13 years, and 73.9% of the patients had family history of chronic kidney disease (CKD). We achieved a molecular diagnostic rate of 50.9%. Four genes accounted for more than 70% of identified pathogenic variants: PKD1 and PKD2 (n = 186, 53.4%), MUC1 (8.9%), and COL4A5 (8.3%). In 162 patients with a genetic diagnosis, excluding PKD1/PKD2, the a priori diagnosis was confirmed in 58% and in 13% the diagnosis was reclassified. A genetic diagnosis was established in 22 (29.7%) patients with CKD of uncertain aetiology. Based on genetic testing, a diagnostic kidney biopsy was unnecessary in 13 (8%) patients. Presence of family history of CKD and the underlying a priori diagnosis were independent predictors (P < 0.001) of a positive genetic diagnosis. CONCLUSIONS: A dedicated GKD clinic is a valuable resource, and its implementation of various genomic strategies has resulted in a direct, demonstrable clinical and therapeutic benefits to affected patients.

The genetic landscape of polycystic kidney disease in Ireland.

Polycystic kidney diseases (PKDs) comprise the most common Mendelian forms of renal disease. It is characterised by the development of fluid-filled renal cysts, causing progressive loss of kidney function, culminating in the need for renal replacement therapy or kidney transplant. Ireland represents a valuable region for the genetic study of PKD, as family sizes are traditionally large and the population relatively homogenous. Studying a cohort of 169 patients, we describe the genetic landscape of PKD in Ireland for the first time, compare the clinical features of patients with and without a molecular diagnosis and correlate disease severity with autosomal dominant pathogenic variant type. Using a combination of molecular genetic tools, including targeted next-generation sequencing, we report diagnostic rates of 71-83% in Irish PKD patients, depending on which variant classification guidelines are used (ACMG or Mayo clinic respectively). We have catalogued a spectrum of Irish autosomal dominant PKD pathogenic variants including 36 novel variants. We illustrate how apparently unrelated individuals carrying the same autosomal dominant pathogenic variant are highly likely to have inherited that variant from a common ancestor. We highlight issues surrounding the implementation of the ACMG guidelines for variant pathogenicity interpretation in PKD, which have important implications for clinical genetics.

Differential impact of smoking on mortality and kidney transplantation among adult Men and Women undergoing dialysis.

BACKGROUND: The extent to which smoking contributes to adverse outcomes among men and women of all ages undergoing dialysis is uncertain. The objective of this study was to determine the differential impact of smoking on risks of mortality and kidney transplantation by age and by sex at dialysis initiation. METHODS: We conducted a population-based cohort of incident U.S dialysis patients (n = 1, 220, 000) from 1995-2010. Age- and sex-specific mortality and kidney transplantation rates were determined for patients with and without a history of cardiovascular disease. Multivariable Cox regression evaluated relative hazard ratios (HR) for death and kidney transplantation at 2 years stratified by atherosclerotic condition, smoking status and age. Analyses were adjusted for demographic characteristics, non-cardiovascular conditions, laboratory variables, socioeconomic and lifestyle factors. RESULTS: The average age was 62.8 (±15) years old, 54 % were male, and the majority was white. During 2-year follow-up, 40.5 % died and 5.7 % were transplanted. Age- and sex-specific mortality rates were significantly higher while transplantation rates were significantly lower for smokers with atherosclerotic conditions than non-smokers (P < 0.01). The adjusted mortality hazards were significantly higher for smokers with pre-existing coronary disease (HR 1.15, 95 % CI (1.11-1.18), stroke (HR 1.21, 1.16-1.27) and peripheral vascular disease (HR = 1.21, 1.17-1.25) compared to non-smokers without these conditions (HR 1.00, referent group). The magnitude of effect was greatest for younger patients than older patients. Contrastingly, the adjusted risks of kidney transplantation were significantly lower for smokers with coronary disease: (HR 0.60, 0.52-0.69), stroke; (HR 0.47, 0.37-0.60), and peripheral arterial disease (HR 0.55, 0.46-0.66) respectively compared to non-smokers without these conditions. CONCLUSIONS: We provide compelling evidence that smoking is associated with adverse clinical outcomes and reduced lifespans among dialysis patients of all ages and sexes. The adverse impact is greatest for younger men and women.

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.

Uncommon side effect with a commonly used targeted agent: sunitinib-induced nephrotic syndrome in a patient with metastatic renal cell carcinoma.

The authors report the case of a 67-year-old woman with metastatic renal cell carcinoma (RCC) without prior nephrectomy, who had received long-term exposure (38 months) to the oral multi-targeted tyrosine kinase inhibitor (TKI), sunitinib. She had a sustained clinical and radiological response to her therapy, but had this therapy discontinued due to the rare development of nephrotic syndrome.

Recurrence of anti-neutrophil cytoplasmic antibody-associated vasculitis in appropriately immunosuppressed renal transplant patients: a discussion of two cases.

BACKGROUND: Granulomatosis with polyangiitis (GPA) (formerly known as Wegener's granulomatosis) is a multisystem autoimmune disease of unknown aetiology. Renal disease manifests as a crescentic glomerulonephritis, with varying degrees of renal failure. Ten percent of patients progress to end-stage kidney disease. Relapse of GPA in renal transplant patients is rare, with a rate of 0.09 relapses per patient per year. PATIENTS AND METHODS: We describe two cases of GPA relapse in immunosuppressed renal transplant patients. RESULTS: These patients presented with new-onset graft disfunction, having previously had an uncomplicated posttransplant course. Both patients were on appropriate doses of immunosuppressive agents at the time of relapse, with therapeutic target levels of tacrolimus. We describe the background history and management of both patients. CONCLUSION: The cases described inform us that although recurrence of anti-neutrophil cytoplasmic antibody vasculitis in transplant patients is rare, it should remain on our list of differential diagnoses in allograft disfunction.

Incidence and outcome of acute renal failure complicating autologous stem cell transplantation for AL amyloidosis.

BACKGROUND: High-dose intravenous melphalan and autologous peripheral blood stem cell transplantation (HDM/SCT) is an effective treatment for AL amyloidosis but is associated with significant toxicity, including the development of acute renal failure (ARF). The incidence and outcome of ARF as a complication of such treatment is not known. METHODS: All AL amyloidosis patients treated with HDM/SCT at a single institution between July 1, 1994 and May 31, 2000 were included in the analysis unless they were dialysis-dependent prior to treatment. Baseline data were collected prospectively. Treatment-related data were obtained from a prospectively maintained database and medical record review. ARF was defined as either a >/=1 mg/dL increase in serum creatinine or a doubling of serum creatinine to >/=1.5 mg/dL for at least 2 days. Recovery of renal function was defined as a return of serum creatinine to less than or within 0.5 mg/dL of the pretreatment value or the ability to discontinue dialysis initiated as a result of ARF. RESULTS: ARF occurred in 37 of 173 patients (21%). Initiation of dialysis was required in nine patients (5%). Forty-six percent of patients with ARF, including four of nine who required dialysis, had recovery of renal function. Baseline clinical variables that were independent predictors of transplant-associated ARF included creatinine clearance, proteinuria, and cardiac amyloidosis. Treatment-related variables associated with ARF included melphalan dose and bacteremia. ARF was associated with reduced survival at 90 days but did not have an impact on overall survival at a median follow-up of 2.9 years. CONCLUSION: ARF is a frequent but often reversible complication of HDM/SCT for AL amyloidosis. Specific clinical and treatment-related factors are associated with the development of this complication.

High-dose intravenous melphalan with autologous stem cell transplantation in AL amyloidosis-associated end-stage renal disease.

BACKGROUND: The development of end-stage renal disease (ESRD) is common among patients with amyloid light-chain AL amyloidosis-associated renal disease and survival of these patients is poor. High-dose intravenous melphalan and autologous stem cell transplantation induce remission of the plasma cell dyscrasia in a significant proportion of patients with AL amyloidosis. The efficacy and tolerability of such treatment for patients with AL amyloidosis-associated ESRD are unknown. METHODS: Between June 1994 and June 2000, 15 patients with AL amyloidosis-associated ESRD were treated with intravenous melphalan (70 to 200 mg/m2) and autologous peripheral blood stem cell transplantation. Clinical and laboratory data were prospectively collected prior to treatment, during the peritransplant period, and at 3 months, 12 months, and annually thereafter. Treatment outcomes and toxicities were compared with 180 non-ESRD patients treated during the study period. RESULTS: Eight of 15 patients (53%) had a hematologic complete response following treatment. Two patients (13%) died during the peritransplant period. Transfusion requirements were greater and there was a trend toward increased severity of mucositis in the ESRD patients compared with the non-ESRD patients. Median survival for the ESRD patients with a hematologic complete response was 4.5 years. Five patients with hematologic complete response have either undergone or are awaiting renal transplantation. CONCLUSION: High-dose intravenous melphalan with stem cell transplantation is an effective treatment in selected patients with AL amyloidosis-associated ESRD. Although the toxicity profile is greater in ESRD patients, the treatment offers the possibility of successful renal transplantation if hematologic remission is achieved. This treatment should be considered for patients with AL amyloidosis-associated ESRD.