Primary Renal Diagnosis Research Articles

The Impact of Primary Renal Diagnosis on Prognosis and the Varying Predictive Power of Albuminuria in the NURTuRE-CKD Study

Plain Language SummaryChronic kidney disease (CKD) is a broad term that describes a reduction in kidney function. However, there are several underlying causes of CKD. Using the NURTuRE-CKD study, we explore how the individual causes of CKD affect the risk of disease progression and how some of the tests we do are more accurate in predicting kidney failure (KF) in some causes of CKD rather than others. We found that a person’s type of kidney disease can significantly impact their risk of KF and death. For example, people with DKD or certain genetic conditions had a higher risk of KF, while those with other types, like tubulointerstitial disease, had a lower risk. Albuminuria, which measures the amount of a protein called albumin in the urine, is commonly used to predict kidney disease progression. However, we found that its effectiveness varies depending on the type of kidney disease. It was most helpful in predicting outcomes for people with vasculitis and DKD but added little value for those with genetic kidney diseases. In conclusion, recognizing the specific type of kidney disease is crucial for accurate risk assessment and effective treatment planning in CKD. This study highlights the importance of a tailored approach to managing kidney disease based on the primary diagnosis.

Incidence of fatal and non-fatal pulmonary thromboembolism after removal of tunnelled central venous haemodialysis catheters without ultrasound scan and anticoagulation.

Catheter related thrombosis is a common complication of tunnelled central venous catheter (TCVC) usage. There are concerns that TCVC removal could dislodge a thrombus to cause pulmonary thromboembolism (PE). The incidence of PE following TCVC removal is unclear and so the aim of this study was to investigate the incidence of PE and whether it is high enough to warrant screening with ultrasound with a view to systemic anticoagulation prior to TCVC removal. 1102 consecutive TCVC removals without ultrasound and systemic anticoagulation were included in this retrospective study. Data were extracted from electronic health records. Measures to identify PE events included: deaths, computed tomography pulmonary angiogram (CT-PA), isotope lung perfusion scans and D-dimers blood tests within 7 days of removal. Of the 1102 TCVC removals, the mean age of patients was 56.9 years and 57.3% were male. The primary renal diagnosis for 24.5% of patients was diabetic nephropathy. There were seven deaths following removal, none of which had PE as a contributing cause on review of their clinical history and death certificates. Five CT-PAs and one isotope lung perfusion scan were carried out in the 7 days after TCVC removal and none had a positive finding of PE. Three patient had D-dimers measured in blood within 7 days and none of these patients were subsequently diagnosed with PE. There was no evidence of fatal or non-fatal PE's occurring in the 7 days following TCVC removal. This would support the practice of removing TCVCs without the need for ultrasound screening and without a period of systemic anticoagulation.

Age-modified risk factors for mortality of non-elderly adult kidney transplant recipients: a retrospective database analysis.

We aimed to investigate the role of the recipient's age strata in modifying the associations between risk factors and mortality in non-elderly adult kidney transplant (KT) recipients (KTR). We stratified 108,695 adult KTRs between 2000 and 2016 with conditional 1-year survival after KT into cohorts based on age at transplant: 18-49years and 50-64years. We excluded KTRs aged < 18years or > / = 65years. KTRs were observed for 5years during the 2nd through 6th years post-KT for the outcome, all-cause mortality. Increasing recipient age strata (18-49-year-old and 50-64-year-old) correlated with decreasing 6-year post-KT survival rates conditional on 1-year survival (79% and 57%, respectively, p < 0.0001). Middle adult age stratum was associated with a higher risk of all-cause mortality than young adult age stratum in KTRs of Hispanic/Latino and other races [HR = 1.23, 95% CI = 1.04-1.45 and HR = 1.51, 95% CI = 1.16-1.97, respectively] and with a primary native renal diagnosis of hypertension or glomerulonephritis [HR = 1.32, 95% CI = 1.12-1.55 and HR = 1.29, 95% CI = 1.10-151, respectively]. When compared with the young adult age stratum, the middle adult age stratum had a mitigating effect on the higher risk of mortality associated with sirolimus-mycophenolate or sirolimus-tacrolimus than the standard calcineurin inhibitor-mycophenolate regimen [HR = 0.75, 95% CI = 0.57-0.99 and HR = 0.71, 95% CI = 0.57-0.89, respectively]. Among adult non-elderly KTRs, the age strata, 18-49years, and 50-64years, have varying modifying effects on the strength and direction of associations between some specific risk factors and all-cause mortality.

Timing and Modality of Kidney Replacement Therapy in Children and Adolescents

IntroductionThe choice and timing of kidney replacement therapy (KRT) is influenced by clinical factors, laboratory features, feasibility issues, family preferences and clinicians´ attitudes. We analyzed the factors associated with KRT modality and timing in a multicenter, multinational prospective pediatric cohort study. Methods695 pediatric chronic kidney disease patients enrolled into the 4C study at age 6 to 17 years with estimated glomerular filtration rate (eGFR) 10 to 60 ml/min/1.73 m2 were investigated. Competing risk regression was performed to identify factors associated with initiation of dialysis or pre-emptive transplantation (Tx), including primary renal diagnosis, demographics, anthropometrics and laboratory parameters. ResultsDuring the 8-year observation period, 342 patients (49%) started KRT. Of these, 200 patients started dialysis whereas 142 patients underwent pre-emptive Tx. A lower eGFR at enrolment (HR (hazard ratio) 0.76 [95% confidence interval 0.74-0.78], a steeper eGFR slope (HR 0.90 [0.85-0.95] and a higher systolic blood pressure standard deviation score (SDS) (HR 2.07 [1.49-2.87]) increased the likelihood of KRT initiation. Patients with glomerulopathies were more likely to start dialysis than children with CAKUT (HR 3.81 [2.52-5.76]). Lower BMI SDS (HR 0.73 [0.6-0.89]) and lower hemoglobin (HR 0.8 [0.72-0.9]) were associated with higher likelihood of dialysis. A significant center effect was observed, accounting for 6.8% (dialysis) to 8.7% (pre-emptive Tx) of explained variation. ConclusionThe timing and choice of KRT in pediatric patients is influenced by the rate of kidney function loss, the underlying kidney disease, nutritional status, blood pressure, anemia and center-specific factors.

#2980 The natural history of urinary tract infections in kidney transplant recipients

Abstract Background and Aims Urinary tract infections (UTIs) can occur following kidney transplantation, but research on infection rates and outcomes is inconclusive. We therefore aimed to provide a comprehensive understanding of the natural history of UTIs and the impact on long-term outcomes. Method We performed a single-centre cohort study of kidney-only transplant recipients at the Glasgow Transplant Unit, UK. A standardised protocol for UTI screening and treatment was in use and only treated UTIs were included. We studied the first two years post-transplant as this is the time when UTIs are most likely to occur. Patients were categorised into 3 groups based on number of UTIs: no UTIs, 1-2 UTIs and ≥3 UTIs. Furthermore, patients with highly recurrent UTIs defined as ≥10 UTIs in the first 2 years were compiled and analysed. Proportional odds logistic regression was performed to identify risk factors for having ≥3 UTIs, with adjustment for age, sex, primary renal diagnosis, donor type (live donor, deceased heart beating, deceased non-heart beating) and induction immunosuppression. Results Amongst 1412 transplant recipients studied over a nine-year period, the mean age was 48 years and 563 (39.9%) were female. 1169 (82.8%) of recipients experienced no UTIs, 180 (12.7%) had 1-2 UTIs, and 63 (4.5%) had ≥3 UTIs (Fig. 1). The key risk factors for developing ≥3 UTIs were female sex: adjusted odds ratio (aOR) 1.50 (95% confidence interval 1.13-1.99), induction with anti-thymocyte globulin (ATG): aOR 6.60 (3.05-14.05), and age: aOR for each one-year increase 1.01 (1.00-1.02). There were no primary renal diagnoses (PRD) that demonstrated a significant association with ≥3 UTIs. However, individuals with tubulointerstitial disease, a group which includes structural abnormalities of the urinary tract and reflux nephropathy as a considerable proportion, showed a trend towards heightened risk: aOR 1.47 (0.97-2.22, reference group glomerulonephritis). Recipients with ≥3 UTIs had lower estimated glomerular filtration rates (eGFRs) at two years compared to the no UTI group (49.7 vs. 59.2mL/min/1.73 m2, respectively). However, there was no significant increase in mortality or graft loss between the three groups. In the group of patients with highly recurrent UTIs, consisting of 14 patients (0.01%), we observed that 3 (21%) had a PRD of reflux nephropathy, while 5 (35%) had underlying structural abnormalities of the native renal tract as a PRD. Further to this 5 (35%) of the patients received ATG induction and 5 (35%) patients had a previous transplant. Conclusion We describe a low rate of UTIs requiring treatment in the first two years after kidney transplantation. Females, older recipients and those given ATG induction were at increased risk of recurrent UTIs. There was no impact of UTIs on graft loss or patient mortality. However, eGFR at two years post-transplant was lower amongst those with recurrent UTIs. We also observed that for the patients with highly recurrent UTIs, ATG induction, previous transplants, reflux nephropathy and structural abnormalities of native renal tract may be a risk factor. Recipients at highest risk of UTIs should therefore be screened for UTIs and interventions to reduce this risk should be considered

#2755 NURTuRE-CKD: outcomes by primary renal diagnosis

Abstract Background and Aims Chronic kidney disease (CKD) represents a major global healthcare challenge, affecting approximately 850 million people worldwide [1], and is an independent risk factor for the progression to kidney replacement therapy (KRT) and all-cause mortality [2]. However, CKD encompasses various causes, each with unique pathophysiology and rates of progression [3]. Here we describe the outcomes from NURTuRE-CKD, an ongoing, multicenter prospective cohort study of 2996 non-dialysis CKD patients, by primary renal diagnosis, aiming to describe the differing rates of progression, ESKD and mortality by CKD cause and provide insights into those at greatest risk. Method Patients with an eGFR of 15–59 mL/min/1.73 m2 or eGFR ≥60 mL/min/1.73 m2 with a uACR &amp;gt;30 mg/mmol were enrolled, in addition to 86 controls. The full study design and methods of NURTuRE-CKD have previously been reported [4]. Outcomes: ESKD, eGFR &amp;lt;15 mL/min/1.73 m2, Transplantation, initiation of KRT, all-cause mortality and serial eGFR data were sourced from the UK Renal Registry. ESKD was defined as initiation of KRT or eGFR &amp;lt;15 mL/min/1.73 m2. Rate of progression was determined via eGFR slope. ERA diagnostic categories were used for primary renal diagnoses, with ‘glomerular diseases’ split into glomerulonephritis (GN) and vasculitis. The Chi-squared test was used to compare categorical variables, and the Kruskal-Wallis test for continuous variables. A multivariable Cox proportional hazards regression analysis predicting the time to ESKD by primary diagnosis was undertaken, using vasculitis as the reference category. Model 2 included adjustments for baseline eGFR. Results Table 1 depicts both the baseline characteristics and outcomes by the 8 diagnosis categories. Average follow-up duration was 53.8 months, not significantly different between the groups, but all other baseline variables differed significantly. The hypertensive/renovascular group were oldest and familial group youngest at 71 and 53 years, respectively. At baseline the diabetic nephropathy (DN) group had the lowest eGFR 28 ml/min/1.73 m2 and highest uACR 88.3 mg/mmol. However, the familial group had the steepest pre-enrolment eGFR decline slope. Delta eGFR during the follow-up period was steepest in the familial group and DN groups at −3.4 and −3.0 ml/min/1.73 m2, respectively, whereas the vasculitis group had slowest progression −0.7 ml/min/1.73 m2. Overall rate of ESKD was 24.7%; lower in the vasculitis (14%), systemic disease (17.7%) and tubulointerstitial (18.8%) groups, and higher in the DN (36.7%) and familial (31.6%) groups. All-cause mortality was greatest in the DN group at 40.4%. Despite being the fastest progressors defined by eGFR slope, the familial group had the lowest mortality rate (5.2%), but they were of younger age and had a high rate of kidney transplantation (10.1%). Unadjusted HRs for ESKD, were significantly higher for all diagnoses except tubulointerstitial and systemic diseases compared to the vasculitis group; DN evidenced the highest hazard ratio at 3.15 (2.18-4.55). When adjusted for baseline eGFR, HRs for the glomerulonephritis 2.04 (1.89-4.03), diabetes 1.5 (1.04-2.16) and familial 2.76 (1.89-4.03) remained significantly higher. Conclusion Rates of progression and incidence of clinically meaningful outcomes differ between CKD causes in NURTuRE. Those with DN and familial conditions had faster eGFR decline and had higher rates of ESKD, with associations persisting despite controlling for baseline eGFR. Recognising that CKD progresses at different rates is crucial, not only for providing personalised care, but also key to understanding differing pathophysiologic mechanisms of progression. NURTuRE-CKD will also explore novel biomarkers, with the aim of illuminating mechanisms of progression, improving risk prediction and highlighting novel drug targets.

#2182 An unexpected life-threatening cause of kidney failure

Abstract Background and Aims Kidney failure can appear in acute clinical conditions and the cause cannot always be determined, as in approximately 40% of cases that require renal replacement therapy (RRT). In addition, there are other cases in which a patient with persistently low estimated glomerular filtration rate (eGFR) for 3 months is treated with RRT without a primary renal diagnosis. Systemic sclerosis (SSc) is a rare condition that can lead to RRT due to renal ”crisis”. Autopsy studies reveal kidney pathology in approximately 60 percent of patients with SSc. In addition, as many as 50 percent of patients with SSc have markers of kidney disease, as manifested by mild proteinuria, elevated serum creatinine concentration, and/or hypertension. The aim of our paper is to describe a case in which hemodialysis was initiated in emergency setting and the diagnosis was established after that. However clinical course was fatal and the final diagnosis was SSc. Method A 65-year-old male patient was admitted to the Nephrology department with a weight loss of 20 kg in 2 years, depression, low appetite and progressive decline of physical strength. He was previously diagnosed with diabetes mellitus (DM) and high blood pressure (HBP), the ponderal loss being attributed to DM. Insulin treatment was initiated together with antihypertensive medication. In the following 3 months, the kidney function deteriorated progressively and hemodialysis was started. Gray scale and CEUS US were performed to assess a possible cause of kidney failure. However, after the commencement of hemodialysis, the clinical condition did not improve and patient died in respiratory failure complicated by continuous pleural effusion. A skin biopsy from the right thigh was performed for the positive diagnosis. Results At clinical evaluation the patient was cachectic, with striking generalized parchment-like skin lesions which were suggestive both for ichthyosis or SSc. Laboratory tests revealed hyperglycemia, anemia, hypoalbuminemia, increased lactate dehydrogenase and creatine kinase (CK), mild proteinuria and glomerular hematuria. On the other side, myositis antibodies (AB) panel, antinuclear AB, tumor markers for pancreas and gastro-intestinal carcinoma, AB for vasculitis and lupus were negative. Ultrasound (US) (grey scale and CEUS) described dilated bile ducts and gallbladder with massive sludge, without evidence of tumoral neovascularization, and shrunk kidneys with hypoechoic medulla. CT scan confirmed the US findings. Dialysis parameters indicated kt/V 1.4 and urea reduction ratio of 79%. Therefore, no metabolic disturbances could explain the severely altered medical status. The clinical condition of the patient made the kidney biopsy unfeasible. Nevertheless, we decided to perform a skin biopsy, which revealed gross collagen bands, absence of sebaceous glands or hair follicles, as well as rare capillaries with lymphocyte inflammatory infiltrate and absence of hypoderma, thus confirming the diagnosis of SSc. Conclusion SSc can present with obscure clinical signs, leading to multiple organ dysfunction and initially unapparent cause of kidney failure. However, clinicians must be aware of potentially suggestive etiological signs such as parchment-like skin lesions and high blood pressure in a patient with multiple comorbidities. One must differentiate a dehydrated skin from a pathognomonic skin lesion as it is in SSc.

#2012 Long term outcomes in patients with primary membranous nephropathy: a retrospective cohort study from a single center

Abstract Background and Aims Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in non-diabetic adults, accounting for almost 30% of biopsy-diagnoses. The degree of proteinuria varies widely from sub-nephrotic (less than 3.5 g/day) to more than 20 g/day. Patients with primary MN who attain either spontaneous or treatment-induced remission, generally, have a good long-term prognosis. Those who reach partial remission fare better than those with stable or progressive disease, while duration of remission- whether spontaneous or due to treatment is linked to better renal outcomes. This study aims to study long-term outcomes in MN patients, identifying risk factors of relapse and treatment non-responsiveness. Method The retrospective cohort study included 40 patients, with available data, diagnosed with primary MN between 2013 and 2023. Data on urinary protein to creatinine ratio (UPCR), serum albumin, estimated glomerular filtration rate (e-GFR), anti-PLA2R-Antibodies (PLA2R-Ab), CD19+ subpopulations, and lipid profile were collected, alongside treatment types over five years. Baseline date was defined as the date of renal biopsy, primary renal diagnosis, or symptom onset. We defined complete remission, partial remission, and relapse based on UPCR: complete remission as a UPCR of less than 300 mg/g, partial remission as a UPCR of less than 3.5 g/g provided there is also a 50% or greater reduction from the baseline UPCR, and relapse as a UPCR greater than 3.5 g/g after a period in which complete or partial remission was achieved. We monitored patients for clinical signs of remission, relapse, and non-response to treatment. Logistic regression was used to identify risk factors for remission and relapse. Additionally, a survival analysis was conducted with the primary endpoint being time to a 40% reduction in e-GFR. Results The mean age at baseline was 55.5 ± 13.2 years, with 70% being men. Mean proteinuria was 11 ± 7.5 g/g, with 75% presenting with nephrotic syndrome, while 34% of them had positive anti-PLA2R Ab. Baseline e-GFR was 75 ± 30.5 ml/min/1.73 m2. 15% (6/40) of patients did not require immunosuppressive treatment and experienced spontaneous remission. 44% (18/40) of total patients received treatment with Rituximab, 35% (14/40) received treatment with modified ponticelli regimen, while the remaining 2 patients required more than 2 different treatments to achieve remission. Complete remission was achieved by 42% of the patients, 41% achieved only partial remission, while the rest 17% did not attain remission. Relapse occurred in 32% of the patients, requiring further immunosuppressive therapy. Positive anti-PLA2R Ab (exp (B) = 15.1 p-value = 0.031) and male gender (exp (B) = 2, =.3 p-value = 0.01) were associated with higher risk of non-response to treatment. Over a follow-up of 5 years, patients with partial remission had a 26-fold times increased risk of relapse (p-value = 0.023,) compared to those with complete remission. Higher baseline UPCR also correlated with an increased relapse risk; a 1g/g increase in UPCR raised relapse risk by 17% (p-value = 0.016, exp (B) = 1.174). Kaplan-Meier survival curves demonstrated that patients achieving any form of remission did not experience the endpoint of 40% reduction in e-GFR (log-rank p-value = 0.007). Conclusion These analyses indicate that achieving and maintaining remission in primary MN is key for preserving e-GFR and preventing kidney progression. Risk factors like male gender, initial heavy proteinuria, and positive PLA2R antibodies need special attention and careful management to optimize patient outcomes.

#1452 Halting the progression of chronic kidney disease; an audit of the use of renin-angiotensin-aldosterone blockers and SGLT-2 inhibitors

Abstract Background and Aims Sodium-glucose cotransporters-2 inhibitors (SGLT2i) were initially developed for the treatment of type 2 diabetes. Multiple studies have demonstrated the renoprotective effect of SGLT2i, with the capacity to slow diabetic kidney disease and non-diabetic proteinuric chronic kidney disease progression. More recently, the EMPA-KIDNEY trial demonstrated a benefit in patients with chronic kidney disease with a wider range of albuminuria and glomerular filtration rate. We aim to identify the proportion of patients on renin-angiotensin aldosterone system blockade (RAASb) such as angiotensin converting enzyme inhibitor (ACEi), and angiotensin II receptor blocker (ARB), and sodium-glucose transporter-2 inhibitor (SGLT2i) in our Nephrology outpatients clinic. We also aim to encourage awareness and prescribing of RAASb and SGLT2i in eligible patients with CKD. Method A prospective audit was performed in Galway University Hospital (GUH) from September 2023 to October 2023. The audit questionnaire was completed by doctors reviewing patients in OPD. The use of ACEi/ARB/SGLT2i was recorded during the consultation. Results 165 patients were included in the audit with a mean (±SD) age of 62.1 ± 18.6 years. The 3 most common primary renal diagnoses were diabetic kidney disease; 20/165 (12.1%), hypertensive renal disease; 18/165 (10.9%) and IgA nephropathy; 15/165 (9.1%). The mean estimated glomerular filtration rate (eGFR) was 46.8 ± 24.5 ml/min/1.73 m². At baseline, 94/165 (57%) were already on RAASb, none on dual RAASb agents. 20/165 (12.1%) were already on SGLT2i, amongst these, 15/20 (75%) were also on RAASb at the time of the OPD consultation. 13/165 (7.9%) patients were maximised on RAASb and 4/165 (2.4%) commenced an SGLT2i at the clinic visit. Guideline directed medical therapy according to the EMPA-Kidney and UK Kidney Association Clinical Practice Guidelines would suggest missed opportunity on therapeutic optimisation with RAASb and SGLT2i in 66/83 (79.5%) patients; 26/66 (39.4%) were neither on RAASb or SGLT2i, 34/66 (51.5%) were on RAASb but not on SGLT2i, 3/66 (4.5%) were on SGLT2i but not on RAASb, and 3/66 (4.5%) were on sub-maximal RAASb with an SGLT2i. Conclusion There is new evidence to support the use of SGLT2i, in those with chronic kidney disease with a wide range of albuminuria. SGLT2i use is underutilised in our clinic. Ideally, these patients should be initiated on an SGLT2i after being established on a RAASb early in their diagnosis to ensure the optimal renoprotective effects of SGLT2i.

#3057 OUTCOMES IN SRNS (FSGS) PATIENTS IN THE UK RADAR IDIOPATHIC NEPHROTIC SYNDROME REGISTRY AND THEIR RELATIONSHIP WITH TIME-AVERAGED PROTEINURIA

Abstract Background and Aims Idiopathic Steroid Resistant Nephrotic Syndrome, SRNS (incorporating FSGS) is an important cause of proteinuric renal disease leading to kidney failure. Here we describe the outcomes of SRNS using the UK National Registry of Rare Kidney Diseases Idiopathic Nephrotic Syndrome (RaDaR-INS) Cohort, including retrospective and prospective data from 4274 patients with nephrotic syndrome (NS) not attributable to glomerulonephritis or systemic disorders, recruited from 107 adult and paediatric kidney units across the UK since 2010. In patients with FSGS, severity of proteinuria at onset and during follow up is associated with renal failure. In this study, we tested for associations between defined proteinuria endpoints with both eGFR slope and renal survival, in children and adults. Method Participants included those with renal biopsy diagnosis of FSGS or minimal change disease (MCD), or monogenic NS. Patients with no proteinuria measurement ≥1.0 g/g &amp;gt;6 months after disease onset were excluded as likely fully steroid-sensitive. Patients with kidney failure (KF) (CKD stage 5 or on renal replacement therapy) at or prior to first proteinuria measurement after baseline were excluded. Disease onset was defined as time of renal biopsy; primary renal diagnosis (PRD) date if no biopsy date recorded, and first proteinuria ≥1 g/g if neither biopsy/PRD date was available. Baseline was defined as first proteinuria ≥1 g/g &amp;gt;6 months after disease onset. Kaplan-Meier methods were used to analyze renal survival, defined as absence of KF or death with survival time calculated from baseline to last follow up. eGFR slope was measured from 6 months after baseline for the duration of follow up. Results Of 612 MCD and FSGS patients meeting eligibility, median time from disease onset to baseline was 1.2 years (IQR 0.6-4.4). Median baseline age was 38 years (IQR 21–56) with paediatric patients representing 21% of the study population. Median proteinuria at baseline was 3.4 g/g (IQR 1.9-6.2), while mean eGFR was 89 mL/min/1.73 m2 (SD 39). Mean rate of loss of eGFR over follow-up was 4.4mL/min/1.73 m2/year (SD 10.9). Complete proteinuria remission (CR) and FSGS partial remission (FPR) were defined as shown in Table 1 using values of time-averaged proteinuria (TA-PU) over months 6–24 from baseline. For patients achieving CR or FPR, the rate of loss of eGFR was slower (Table 1), with a higher probability of survival from KF/death (Table 1 &amp; Figure 1), than patients failing to achieve CR or FPR. Conclusion This is a study of proteinuria and outcomes in a population of patients with FSGS or steroid-resistant MCD. We regard the latter group as likely also to have FSGS. In this population of patients with overt proteinuria, achieving partial or complete remission of proteinuria is associated with slower disease progression and reduced risk of KF/death.

#3102 LIMITED PHARMACEUTICAL LITERACY IN PATIENTS ON HEMODIALYSIS IN THE NETHERLANDS AS ASSESSED WITH THE RALPH INTERVIEW GUIDE

Abstract Background and Aims Patients with advanced chronic kidney disease typically use 15 or more different drugs. Proper use of these drugs requires sufficient pharmaceutical literacy, which is defined as health literacy in the context of medication use. Until now, no data are available on the prevalence of limited pharmaceutical literacy in patients with CKD or on hemodialysis. Recently, the RALPH (Recognizing and Addressing Limited Pharmaceutical Literacy) interview guide was developed in the Netherlands to assess pharmaceutical literacy skills. The current study aims to provide data on the prevalence of limited pharmaceutical literacy, associated problems, and the domains in which these problems occur, in hemodialysis patients using phosphate-binding drugs in the Netherlands. Method This study was part of a prospective observational study in a teaching hospital in Rotterdam, investigating a complex adherence-improving intervention in hemodialysis patients using phosphate-binding drugs. One of the aims of the original study was to explore pharmaceutical literacy at baseline, using the RALPH interview guide. The RALPH consists of eleven multiple-choice questions and several open-ended questions in three health literacy domains. The functional domain assesses the basic skills of reading, writing, and calculating. The communicative domain assesses more advanced skills, namely finding and understanding information and applying this information to the own situation. The critical domain assesses the even more advanced skills of critically analyzing information and applying this information to different situations. Limited pharmaceutical literacy was defined as the presence of at least one problem in one or more of the domains of the RALPH. The primary outcome was the prevalence of limited pharmaceutical literacy. Secondary outcomes were the prevalence of one or more problems in the domains. Data were analyzed using descriptive statistics (SPSS version 28.0). Results A total of 63 patients were included in the study. Mean age was 66 years, 65% were male. The main primary renal diagnoses were hypertensive nephropathy (31%) and diabetic nephropathy (19.1%). Seventy-three percent of patients received their drugs in a weekly drug dispensing system. The prevalence of limited pharmaceutical literacy was 79%. Fifty-two percent of patients had at least one problem in the communicative domain, 46% in the functional domain, and 78% in the critical domain. Around 90% of patients could correctly reproduce user instructions for phosphate-binding drugs. The most prevalent problems were lack of knowledge about the indication (40%) in the functional domain and finding understandable information (51%) in the communicative domain. In the critical domain, the most frequently encountered problems were a lack of adequate judgment of both reliability and applicability of information (62% and 65%, respectively). Almost half of the patients did not search for information. Furthermore, 32% of patients did not engage in shared-decision making or found this difficult to do. Reasons for this were a profound trust in the nephrologist and the patient's conviction that the nephrologist knew what was best. Conclusion Limited pharmaceutical literacy is frequent in patients on hemodialysis: the majority of patients have problems with finding understandable information and judging its applicability and reliability. The results of this study are in line with earlier findings studying pharmaceutical literacy in Dutch community pharmacies in the Netherlands. However, the current study found slightly higher percentages for problems with finding understandable information and judging the applicability of information. This was expected, as our population generally uses more drugs and has a more vulnerable health status. Recent data show that limited health literacy in general negatively affects certain aspects of self-management, such as adherence, communication, and knowledge. This is also apparent in our study. These data together underline the need for dialysis healthcare providers to individualize their communication and support to meet their patients’ needs.

Benefits of early transplantation in patients with chronic renal failure undergoing coronary revascularization

Objective: This study aimed to evaluate the effectiveness of post-revascularization surgery in reducing future cardiac events among kidney transplant candidates. Additionally, the role of non-invasive diagnostic techniques and the use of coronary angiography in determining the prognosis of patients scheduled for kidney transplantation were examined. Material and Methods: A retrospective analysis was conducted on 202 renal transplant recipients who underwent their first coronary revascularization procedure after initiating renal replacement therapy between January 2021 and December 2021. Demographic data collected included patient age, sex, race, duration of prior end-stage renal disease, and primary renal diagnosis. Results: The study population consisted of 120 men and 82 women, with a mean age of 56.9 years. Diabetes mellitus (DM) and hypertension (HT) were present in 58.4% and 89.6% of the patients, respectively. Coronary angiography was performed in 30% of patients considered at risk. The median graft rejection time was 145 days according to Kaplan-Meier analysis. Discussion: Coronary artery disease (CAD) has a significant negative impact on the pre-, intra-, and post-transplant survival of patients with chronic kidney disease. Myocardial revascularization is recommended in selected patients with unstable cardiac symptoms or chronic kidney disease, providing long-term survival benefits. Collaborative decision-making between cardiologists and nephrologists is crucial to provide optimal care for this high-risk patient population. Lifestyle modifications, risk factor control, and careful patient selection for myocardial revascularization are key in managing coronary artery disease in chronic kidney disease patients. Conclusion: Managing coronary artery disease in chronic kidney disease patients, especially those who are candidates for kidney transplantation, requires a comprehensive approach. Optimal treatment strategies should consider the intricate relationship between cardiovascular and renal factors. Collaborative care involving cardiologists, nephrologists, and transplant specialists, as well as a focus on both myocardial revascularization and medical therapy, can lead to improved outcomes. Further research is needed to refine treatment guidelines and strategies for this high-risk patient population.

MO034: Novel MUC1 variant identified by massively parallel sequencing explains interstitial kidney disease in a large Dutch family

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) can be caused by a wide variety of systemic and renal disorders. In approximately 20% of patients, the cause of CKD remains unknown. Previous studies have shown that massively parallel sequencing (MPS) can be a valuable diagnostic tool in patients with unexplained CKD. Here, we describe a large family with kidney failure of unknown origin, in which we aimed to identify the primary renal disease diagnosis with MPS in a routine healthcare setting. METHOD We conducted MPS in a large family in the Netherlands including six generations with documented kidney failure at young age. Affected individuals had a bland sediment and kidney biopsy revealed interstitial fibrosis in several family members. Whole exome sequencing followed by variant filtering and analysis based on the CKD-Y (CKD-young) gene panel (v18.1, 141 genes) was performed by the Genome Diagnostics Section of the University Medical Center Utrecht. RESULTS MPS revealed a novel frameshift variant [c.326_350dup, p.(Ser119Profs*119), NM_001 204 286.1] in MUC1, which co-segregated with the renal phenotype in the family. This variant is positioned before the first variable number of tandem repeat (VNTR) domain of MUC1 and leads to a + 1 base frameshift in the open reading frame of the MUC1 mRNA. The predicted C-terminal amino-acid sequence of the resulting mutant protein is the same as the previously reported pathogenic cytosine insertions in the VNTR. Variants in MUC1 are associated with autosomal dominant tubulointerstitial kidney disease (ADTKD), which matches the clinical phenotype in this family. Immunohistochemical analysis in the index patient showed MUC1fs deposition in kidney tissue, confirming the diagnosis of ADTKD-MUC1. CONCLUSION We report a novel frameshift mutation in MUC1 identified with MPS. This study highlights that MUC1 variants positioned before the first VNTR region can lead to ADTKD and that genetic testing in patients with suspected ADTKD-MUC1 should also include regions outside of the VNTR. Additionally, this study confirms the relevance of MPS as a tool to screen adult patients with early-onset kidney failure.

Identification of factors associated with high-cost use of inpatient care in chronic kidney disease: a registry study

ObjectiveTo explore factors behind inpatient admissions by high-cost users (HCUs) in pre-end-stage chronic kidney disease (CKD).DesignRetrospective analysis of CKD.QLD Registry and hospital admissions of the Queensland Government Department of Health...

Stage–specific incidence trends of renal cancers in the East of England, 1999–2016

ObjectivesTo determine stage-specific time-trends in renal cancer incidence. MethodsWe used population-based East Anglia data 1999−2016 (population ∼2 million) on 5,456 primary renal cancer diagnoses, estimating stage-specific annual incidence using Poisson regression, allowing for changing time-trends, and adjusting for sex, age, and socioeconomic deprivation. ResultsRenal cancer incidence increased from 9.8–16.4 cases per 100,000 during 1999−2016. Incidence of Stage I, II, and III cases increased over time, most steeply for Stage I, with annual Incidence Rate Ratio [IRR] for Stage I of 1.09 (95 % CI 1.07–1.12) during 1999−2010; and 1.03 (1.00–1.05) during 2011−2016. In contrast, the annual incidence of Stage IV renal cancer decreased during most years, IRR of 0.99 (0.98–1.00) during 2003−2016. ConclusionThe findings are consistent with both earlier detection of symptomatic renal cancer and increasing identification of asymptomatic lesions. However, the decreasing incidence of late-stage disease suggests genuine shifts towards earlier diagnosis.

Using electronic AKI alerts to define the epidemiology of acute kidney injury in renal transplants

BackgroundLittle is known regarding the impact of acute kidney injury (AKI) on renal transplant outcome. Our aim was to define the incidence and outcome of AKI in renal transplant patients using data collected from a national AKI electronic alert systemMethodsThe study represents a prospective national cohort study collecting data on 1224 renal transplants recipients with a functioning renal transplant, between April 2015 and March 2019.ResultsFour hundred forty patients experienced at least one episode of AKI giving an incidence rate of 35.4%. Sixty-four point seven% of episodes were AKI stage 1, 7.3% AKI stage 2 and 28% AKI stage 3. Only 6.2% of episodes occurred in the context of rejection. Forty-three point five% of AKI episodes were associated with sepsis. AKI was associated with pre-existing renal dysfunction, and a primary renal diagnosis of diabetic nephropathy. AKI was more prevalent in recipients from a donor after cardiac death (26.4% vs. 21.4%, p < 0.05) compared to the non-AKI cohort. Following AKI, 30-day mortality was 19.8% and overall mortality was 34.8%, compared to 8.4% in the non AKI cohort (RR 4.06, 95% CI 3.1–5.3, p < 0.001). Graft survival (GS), and death censored graft survival (DCGS) censored at 4 years, in the AKI cohort were significantly lower than in the non AKI group (p < 0.0001 for GS and DCGS).ConclusionThe study provides a detailed characterisation of AKI in renal transplant recipients highlighting its significant negative impact on patient and graft survival.

P1468ASSESSING THE BURDEN OF CHRONIC PAIN IN PATIENTS UNDERGOING HAEMODIALYSIS: A CROSS-SECTIONAL OBSERVATIONAL STUDY

Abstract Background and Aims Chronic pain is a global health problem estimated to affect between 20- 50% of the population and is associated with increased hospitalisations placing a significant burden on healthcare resources. The burden of chronic pain is thought to be especially high in patients undergoing renal replacement due to underlying co-morbidities such as diabetes, peripheral vascular disease and renal bone disease. There is, however, a lack of data out with the United States quantifying the burden in patients undergoing chronic dialysis. The aim of this study was to establish the burden of chronic pain through examination of prescribing records in patients undergoing chronic dialysis. Method We performed a cross sectional observational study in 2 Scottish health boards (together serving 1.9 of Scotland’s 5 million population). Data were collated on age, dialysis vintage, primary renal diagnosis and analgesia prescribing specifically examining whether patients were prescribed paracetamol, non-steroidal anti-inflammatory agents, opioids or gabapentinoids. Descriptive statistics were performed. Results 721 patients receiving haemodialysis were included in the analysis (141 from the Tayside area and 580 from Greater Glasgow and Clyde). Mean age was 64 years old (SD 14.4) with a median time since commencing renal replacement therapy of 3 years (IQR 1.4-6.4). The primary renal diagnosis was diabetes for 28% of the patients, multisystem diseases for 21.6%, interstitial nephropathies for 21.5%, primary glomerulonephritis for 15.8%, and unknown or related to another disease for 10%. Of these 527 (73%) were prescribed a form of analgesia. 404 patients (56%) were prescribed paracetamol, 14 (1.9%) were prescribed a non-steroidal anti-inflammatory, 96 (35.4%) an opioid, 71 (9.8%) a combination of paracetamol with opioid, 170 (23.6%) a gabapentinoid and 100 (14%) were prescribed both a gabapentinoid and opioid. There was no difference in age between those receiving analgesia and those who were not (63.5 vs 65.2, p=0.13). However patients receiving opioids were significantly younger than those who were not prescribed any opioid (62.2 SD 13.9 vs 65 SD 14.5, p-value = 0.001; Wilcoxon rank sum test). There was no difference in percentage of patients receiving analgesia by primary renal diagnosis: Figure 1 (Chi-square test, p=0.1). Conclusion Prescribing rates of analgesia are high in patients undergoing chronic dialysis suggesting a high burden of chronic pain. Number of patients receiving analgesia (in red) or not (in blue), depending on their primary renal diagnosis. 1=primary glomerulonephritis, 2=interstitial nephropathies, 3=multisystem diseases, 4=diabetic nephropathy, 5=not known or other

P1331OPTIMAL PLANNING OF VASCULAR ACCESS IS CALLED FOR IN WOMEN. AVF ARE MORE INTERVENED AND ABANDONED DESPITE LESS CO-MORBIDITY

Abstract Background and Aims Central venous catheter (CVC) increase the risk of infection, central stenosis, hospitalizations, morbidity, mortality and later arterio-venous (AV) access failure. Vascular access planning begins in the predialysis stage of Chronic Kidney Disease (CKD). An optimal timely referral to vascular surgeon is possible since 80 % of patients are known to kidney units before initiating hemodialysis (HD). Despite this, some 71 % (75% women and 68 % men respectively) of incident patients had a CVC as vascular access when starting HD in Sweden during 2017. Some reports have shown increased risk of AVF failure in women which has been contradicted by others. The aim of this study was to determine factors of importance for achieving a functioning fistula for women and men. Method Data from the national Swedish Renal Registry (SRR), that covers the disease progression from CKD phase to renal replacement therapy, was used as well as mandatory national registries. Data was extracted from 2011 to 2017 for, sex, age, primary renal diagnosis, number of CVC, patient phase, co-morbidity, socio-economic factors as well as interventions and complications. A Royston-Palmer model was used for hazard ratio (HR). Cumulative incidence plots were used for fistula patency. P value &amp;lt; .005 was considered significant Results The study included 5040 patients at baseline (33% women). The mean age, the time in dialysis before fistula placement and numbers of CVC did not differ between the sexes. Prevalence of polycystic kidney disease was the only primary diagnosis that differed between the sexes (10.7% among women versus 6.5% among men respectively p&amp;lt;.01). Cancer, hypertension and ischemic heart disease, was more prevalent among men (24.0 vs 19.1 p&amp;lt;.001, 80,9% vs 75.7, p&amp;lt;.001 and 25.3 vs 18.0 p&amp;lt;001). Education level were similar between the sexes whereas more men were married and born in Sweden as compared women (49.3 vs 41.6 p&amp;lt;.001 and 78.9 vs 73.0 p&amp;lt;.001). Age, diabetes and peripheral arterial disease increased the risk for reinterventions by 6% and 28% and 36% (HR 1.06 [1.03,1.15], 1.28[1.18,1.40], and 1.36[1.19,1.56] respectively. The risk for reintervention and abandonment was higher for women (HR 1.19 [95% CI: 1,09,1,56, and 1.42[1,26,1.60)]. Figure 1. shows cumulative incidence for primary patency in lower arm fistula for men and women. Incidence of secondary patency abandonment is higher for women with lower and upper arm AVF while no differences between men and women were observed for AV grafts. Conclusion When receiving the first fistulas, men present a higher co-morbidity as compared to women while age and time of dialysis with a CVC is similar between the sexes. Only 42% will receive an AVF in CKD phase with detriment for men. The consequence of placement in CKD phase could matter and needs to be further analysed. AVF confers a higher risk for reintervention and abandonment, particularly among women which may explain the higher use of CVC. This higher risk must be taken into account when planning for vascular access and follow up.

Survival of South African patients on renal replacement therapy.

BackgroundThe majority of South Africans rely on a resource-constrained public healthcare sector, where access to renal replacement therapy (RRT) is strictly rationed. The incidence of RRT in this sector is only 4.4 per million population (pmp), whereas it is 139 pmp in the private sector, which serves mainly the 16% of South Africans who have medical insurance. Data on the outcomes of RRT may influence policies and resource allocation. This study evaluated, for the first time, the survival of South African patients starting RRT based on data from the South African Renal Registry.MethodsThe cohort included patients with end-stage kidney disease who initiated RRT between January 2013 and September 2016. Data were collected on potential risk factors for mortality. Failure events included stopping treatment without recovery of renal function and death. Patients were censored at 1 year or upon recovery of renal function or loss to follow-up. The 1-year patient survival was estimated using the Kaplan–Meier method and the association of potential risk factors with survival was assessed using multivariable Cox proportional hazards regression.ResultsThe cohort comprised 6187 patients. The median age was 52.5 years, 47.2% had diabetes, 10.2% were human immunodeficiency virus (HIV) positive and 82.2% had haemodialysis as their first RRT modality. A total of 542 patients died within 1 year of initiating RRT, and overall 1-year survival was 90.4% [95% confidence interval (CI) 89.6–91.2]. Survival was similar in patients treated in the private sector as compared with the public healthcare sector [hazard ratio 0.93 (95% CI 0.72–1.21)]. Higher mortality was associated with older age and a primary renal diagnosis of ‘Other’ or ‘Aetiology unknown’. When compared with those residing in the Western Cape, patients residing in the Northern Cape, Eastern Cape, Mpumalanga and Free State provinces had higher mortality. There was no difference in mortality based on ethnicity, diabetes or treatment modality. The 1-year survival was 95.9 and 94.2% in HIV-positive and -negative patients, respectively. One-fifth of the cohort had no data on HIV status and the survival in this group was considerably lower at 77.1% (P < 0.001).ConclusionsThe survival rates of South African patients accessing RRT are comparable to those in better-resourced countries. It is still unclear what effect, if any, HIV infection has on survival.

SAT-211 SURVIVAL OF SOUTH AFRICAN PATIENTS ON RENAL REPLACEMENT THERAPY

In South Africa, the majority of patients rely on a resource-constrained public healthcare system, where access to renal replacement therapy (RRT) is strictly rationed. The prevalence of RRT in the public health care sector (68 per million population, pmp) is less than one-tenth the prevalence in the private healthcare sector (798 pmp). Data on the outcomes of RRT, such as survival, may influence policies and resource allocation. Our aim was to evaluate, for the first time, the survival of South African patients on RRT. We were particularly interested in the effect of healthcare sector on survival and, given South Africa’s HIV epidemic, the effect of HIV on survival. SARR data were used to estimate 1-year survival in patients on RRT. The incident cohort included patients who initiated treatment between January 2013 and September 2016. The prevalent cohort included those on RRT on 31 December 2015. Data were collected on potential risk factors for mortality, including age, ethnicity, primary renal diagnosis (PRD), first RRT modality, HIV status, healthcare sector (public or private), and province of residence . Failure events included stopping treatment without recovery of renal function, and death. Patients were censored if they were alive on RRT at 1 year, recovered renal function, or were lost to follow-up. The Kaplan-Meier method was used to estimate one-year survival. Multivariable Cox regression was used to examine the association of potential risk factors with survival in incident patients, while logistic regression was used in prevalent patients. In the incident cohort (n=6187), the mean age was 51.8 years, 54% were black, 44% were diabetic, 10% were HIV positive, and 82% had haemodialysis (HD) as their first RRT modality. Overall 1-year survival was 90.4% (95%CI 89.6-91.2). Higher mortality was independently associated with older age, end-stage kidney disease (ESKD) of unknown aetiology, and province of residence. More specifically, patients residing in Eastern Cape, Free State, Mpumalanga and Northern Cape had worse one-year survival compared to those residing in the Western Cape. There were no differences in mortality based on ethnicity, diabetic status or healthcare sector. One-year survival was 95.7% and 93.8% in HIV-positive and HIV-negative patients, respectively. One-fifth had no data on HIV-status and the survival in this group was considerably lower at 74.8% (p<0.001). In the prevalent cohort (n=10155), baseline characteristics and one-year survival were similar to that of the incident group. Higher mortality was independently associated with older age and diabetes mellitus. Furthermore, higher mortality was associated with HD as a treatment modality when compared to kidney transplantation. The survival rates of South African patients who access chronic dialysis and transplantation services are comparable to those in better-resourced countries. Although the RRT prevalence in the public health sector is low, the survival of those patients who are accommodated is good, and this should encourage government to increase access to life-sustaining RRT. It is still unclear what effect, if any, HIV status has on patient survival.