Familial Variability of Disease Severity in Adult Patients With ADPKD.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic nephropathy and has striking familial variability of disease severity. Methods: To better comprehend familial phenotypic variability, we analyzed clinical and pedigree data on 92 unrelated ADPKD kindreds with ≥2 affected individuals (N = 292) from an Irish population. All probands underwent genetic sequencing. Age at onset of kidney failure (KF), decline in estimated glomerular filtration rate (eGFR), predicting renal outcome in polycystic kidney disease (PROPKD) score, and imaging criteria were used to assess and grade disease severity as mild, intermediate, or severe. One mild and 1 severe case per family defined marked intrafamilial variability of disease severity. Results: Marked intrafamilial variability was observed in at least 13% of the 92 families, with a higher proportion of families carrying PKD1-nontruncating (PKD1-NT) variants. In families with ≥2 members affected by KF, the average intrafamilial age difference was 7 years, and there was no observed difference in intrafamilial variability of age at KF between allelic groups. The prespecified criteria showed marked familial variability in 7.7%, 8.4%, and 24% for age at KF, the PROPKD score, and imaging criteria, respectively. In our multivariate mixed-effects model, the intrafamilial variability in kidney survival was independent of the measured genotypic factors associated with prognosis and survival (P = <0.001). Conclusion: Using objective measures, we quantified marked intrafamilial variability in ADPKD disease phenotype in at least 13% of families. Our findings indicate that intrafamilial phenotypic variability remains incompletely understood and necessitates a more thorough identification of relevant clinical and genotypic factors.

Twice versus thrice weekly hemodialysis: A systematic review.

INTRODUCTION: Thrice weekly hemodialysis (HD) is currently the norm in high income countries but there is mounting interest in twice weekly HD in certain settings. We performed this systematic review to summarize the available evidence comparing twice to thrice weekly HD. METHODS: A systematic literature search was performed in Ovid MEDLINE, Ovid Embase, and the Cochrane Central Register of Controlled Trials to identify cohort and randomized controlled trials evaluating outcomes of twice versus thrice weekly HD. The bibliographies of identified studies were hand searched to find any additional studies. Risk of bias was assessed using the Newcastle-Ottawa scale for observational studies. FINDINGS: No randomized controlled trials and 21 cohort studies were identified. Overall study quality was modest with high risk of selection bias and inadequate controlling for confounders. The most commonly evaluated outcome measures were survival and residual kidney function. No studies assessed quality of life. Study results were variable and there was no clear signal for overwhelming risk or benefit of twice versus thrice weekly HD with the exception of residual kidney function which consistently showed slower decline in the twice weekly group. DISCUSSION: There is a paucity of high quality data comparing the risks and benefits of twice vs thrice weekly HD. Randomized controlled trial evidence is required to inform clinicians and HD prescription guidelines.

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.

Home-to-home dialysis transition: A 24-year single-centre experience.

Home dialysis (peritoneal dialysis (PD) and home haemodialysis (HHD)) are ideal options for kidney replacement therapy (KRT). Occasionally, because of technique failure, patients are required to transition out of home dialysis, and the most common option tends to be to in-centre HD. There are few published studies on home-to-home transition (PD to HHD or HHD to PD) and dynamics during the transition period. We present a retrospective review of 28 patients who transitioned from a home-to-home dialysis modality at our centre over a 24-year period. We observed a total of 911 home dialysis patients with technique failure (826 PD patients and 85 HHD patients) with only 28 patients (3% of the total with technique failure) having successful home-to-home transition. During the transition period, 11 patients (39%) were hospitalized and 13 patients (46%) required variable periods of in-centre HD. After a median follow-up of 48 months following dialysis modality transition, four patients switched to in-centre HD permanently (home dialysis technique survival of 86% censored for death and kidney transplantation) and four patients died resulting in a patient survival of 86% (censored for switch to in-centre HD and transplantation). In our centre, home-to-home transition is a feasible strategy with comparable patient and technique survival. A significant proportion of patients switching from a home-to-home dialysis modality required variable intervals of hospitalization and in-centre HD during transitions. Future efforts should be directed towards assessment and home dialysis education during the entire process of dialysis transition.

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.

The need for outpatient back-up for home hemodialysis patients: Implications for resource utilization.

INTRODUCTION: The provision of sufficient support contributes to home hemodialysis (HHD) technique survival. The need for back-up treatment in incident and prevalent patients on HHD has not been well described previously, and is important from both technique survival and resource allocation. We aimed to quantify the amount of back-up treatment given to patients in our HHD unit, and hypothesized that the provision of back-up HD facilitated technique survival. METHODS: This was a retrospective, single-center cohort study quantifying the provision of back-up HD between January and December 2018. Electronic and paper medical records were accessed for data collection. FINDINGS: One hundred and nineteen patients dialyzed independently at home during the study period (96 patient years of HHD). Seventy-eight (66%) patients required a total of 292 back-up HD sessions in the HHD unit, representing an average of three back-up HD runs per patient year of HHD. Fifty-three percent of back-up HD runs were required for vascular access related issues. The most common clinical issue requiring assessment and back-up HD was extracellular fluid volume management. An equal proportion (95%) of those that utilized back-up HD and those that did not utilize back-up HD maintained a positive disposition (transplant or ongoing HHD) in relation to technique survival in the short term. CONCLUSIONS: From a resource viewpoint, this program of approximately 100 HHD patients required the availability of one to two staffed HD stations each weekday for back-up HD. The provision of back-up HD was not a harbinger of HHD discontinuation.

Surveillance of common infections in the early period after renal transplantation in a national center: 2014-2017.

BACKGROUND: Infection prevention and timely and effective treatment are among the major aims of care in kidney transplant recipients. Pre-transplant vaccination and pre-transplant viral screening have been extensively studied and are now considered standard practice. Early post-operative infection surveillance is mandatory in other vulnerable cohorts, but has not been extensively studied in this population. We hypothesized that surveillance of the most common bacterial infection types in the post-transplant setting would be beneficial and identify key areas for improvement. METHODS: All adult kidney transplant recipients whose surgeries were performed in the Irish national kidney transplant unit over a 1-year period had prospective early post-transplant (first 30 days) infection surveillance in 2014 for surgical site infection, urinary tract infection, and secondary bloodstream infections (Group T0). Several key changes were implemented following scrutiny of infection patterns and clinical practice. Subsequently, infection surveillance was undertaken for 2016 and 2017 (Group T1) to assess the impact of these changes. RESULTS: Between 2014 and 2017, the number of kidney transplants increased by 32%. The following aspects of clinical practice were the focus of change following analysis of Group T0 data: timing of surgical antimicrobial prophylaxis (SAP) administration, choice of SAP antimicrobial agent, and routine microbiological testing in the peri-operative period. Following implementation of these changes, the timing of SAP administration was greatly improved (45%-100% of cases appropriately timed). The infection rate decreased from 8.9% to 7.4% in 2016, with a further decrease to 4% in 2017 (OR 0.42 (95% CI: 0.16-1.10); P = .08). Compliance with pre-operative microbiological screening improved in Group T1. CONCLUSIONS: Simple clinical practice changes, implemented upon analysis of common bacterial infection surveillance data in the first 30 days after kidney transplantation resulted in more effective SAP administration and improved compliance with routine microbiological testing in the peri-operative period. These interventions have potentially contributed to reduced early post-operative infection rates, despite increased transplant activity in the unit. Infection surveillance is an important and under-utilized way of reducing infections in this vulnerable patient cohort.

Are adverse events in newly trained home dialysis patients related to learning styles? A single-centre retrospective study from Toronto, Canada.

OBJECTIVES: Home haemodialysis (HD) and peritoneal dialysis (PD) have seen growth in utilisation around the globe over the last few years. However, home dialysis, with its attendant technical complexity and risk of adverse events continues to pose challenges for wider adoption. We examined whether differences in patients' learning styles are associated with differing risk of adverse events in both home HD and PD patients. DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital in Toronto, Ontario, Canada. PARTICIPANTS: One hundred and eighteen prevalent adult (≥18 years) home dialysis patients (40 PD and 78 home HD) were enrolled. Patients on home dialysis for less than 6 months or receiving home nursing assistance for dialysis were excluded from the study. INTERVENTIONS: Enrolled patients completed (VARK) Visual, Aural, Reading-writing and Kinesthetic questionnaires to determine learning styles. PRIMARY AND SECONDARY OUTCOME MEASURES: Home HD and PD adverse events were identified within 6 months of completing home dialysis training. Event rates were then stratified and compared according to learning styles. RESULTS: Thirty patients had a total of 53 adverse events. We used logistic regression analysis to determine unadjusted and adjusted ORs for a single adverse event. Non-visual learners were 4.35 times more likely to have an adverse event (p=0.001). After adjusting for age, gender, dialysis modality, training duration, dialysis vintage, prior renal replacement therapy, visual impairment, education and literacy, an adverse event was still four times more likely among non-visual learners compared to visual learners (p=0.008). A subgroup analysis of home HD patients showed adverse events were more likely among non-visual learners (OR 11.1; p=0.003), whereas PD patients showed a trend for more adverse events in non-visual learners (OR: 1.60; p=0.694). CONCLUSIONS: Different learning styles in home dialysis patients exist. Visual learning styles are associated with fewer adverse events in home dialysis patients within the first 6 months of completing training. Individualisation of home dialysis training by learning style is warranted.

Renal transplant outcomes in patients with autosomal dominant tubulointerstitial kidney disease.

INTRODUCTION: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare genetic cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). We aimed to compare renal transplant outcomes in people with ESRD due to ADTKD to those with other causes of renal failure. METHODS: Patients with clinical characteristics consistent with ADTKD by the criteria outlined in the 2015 KDIGO consensus were included. We compared ADTKD transplant outcomes with those of 4633 non-ADTKD renal transplant recipients. RESULTS: We included 31 patients who met diagnostic criteria for ADTKD in this analysis, 23 of whom had an identified mutation (28 were categorized as definite-ADTKD and 3 as suspected ADTKD). Five patients received a second transplant during follow-up. In total, 36 grafts were included. We did not identify significant differences between groups in terms of graft or patient survival after transplantation. Twenty-five transplant biopsies were performed during follow-up, and none of these showed signs of recurrent ADTKD post-transplant. CONCLUSION: In patients with ESRD due to ADTKD, we demonstrate that transplant outcomes are comparable with the general transplant population. There is no evidence that ADTKD can recur after transplantation.

Screening for sleep disorders in patients with advanced chronic kidney disease or end-stage kidney disease
.

INTRODUCTION: Sleep disorders are common in patients with advanced chronic kidney disease (CKD) or end-stage kidney disease (ESKD). Polysomnography (PSG) is the gold standard diagnostic tool but is not easily available in all jurisdictions. We aimed to evaluate various questionnaires and wrist actigraphy as screening tools for sleep disorders in the context of ESKD, by comparing results to unattended home PSG results. MATERIALS AND METHODS: Consecutive patients with advanced CKD or ESKD were recruited and assessed using a combination of self-reported instruments (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, International Restless Legs Questionnaire, Short Form 36), wrist actigraphy, and unattended home PSG. The utility of the questionnaires was summarized. Agreement between acti-graphy and PSG scores was assessed. RESULTS: There was a high prevalence of self-reported sleep disturbance among the 54 participants. The questionnaires had low positive and negative predictive values for their corresponding PSG-measured variables. There were no significant differences between paired PSG and actigraphy summary results for sleep efficiency and time spent awake after sleep onset (n = 27 paired comparisons). CONCLUSION: Commonly used screening questionnaires do not accurately predict sleep disorders in the context of advanced CKD or ESKD. Wrist actigraphy accurately identifies those with low sleep efficiency and long time spent awake after sleep onset, who are likely to have the highest diagnostic yield with PSG. Neither approach obviates the need for PSG for accurate diagnosis of sleep disorders in this population.

Utility of Genomic Testing after Renal Biopsy.

BACKGROUND: Renal biopsy is the mainstay of renal pathological diagnosis. Despite sophisticated diagnostic techniques, it is not always possible to make a precise pathological diagnosis. Our aim was to identify a genetic cause of disease in patients who had undergone renal biopsy and determine if genetic testing altered diagnosis or treatment. METHODS: Patients with suspected familial kidney disease underwent a variety of next-generation sequencing (NGS) strategies. The subset of these patients who had also undergone native kidney biopsy was identified. Histological specimens were reviewed by a consultant pathologist, and genetic and pathological diagnoses were compared. RESULTS: Seventy-five patients in 47 families underwent genetic sequencing and renal biopsy. Patients were grouped into 5 diagnostic categories based on pathological diagnosis: tubulointerstitial kidney disease (TIKD; n = 18); glomerulonephritis (GN; n = 15); focal segmental glomerulosclerosis and Alport Syndrome (n = 11); thrombotic microangiopathy (TMA; n = 17); and nonspecific pathological changes (n = 14). Thirty-nine patients (52%) in 21 families (45%) received a genetic diagnosis; 13 cases (72%) with TIKD, 4 (27%) with GN, 6 (55%) with focal segmental glomerulosclerosis/Alport syndrome, and 10 (59%) with TMA and 6 cases (43%) with nonspecific features. Genetic testing resulted in changes in understanding of disease mechanism in 21 individuals (54%) in 12 families (57%). Treatment would have been altered in at least 26% of cases (10/39). CONCLUSIONS: An accurate genetic diagnosis can result in changes in clinical diagnosis, understanding of pathological mechanism, and treatment. NGS should be considered as a complementary diagnostic technique to kidney biopsy in the evaluation of patients with kidney disease.

An Exome Sequencing Study of 10 Families with IgA Nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is a heterogeneous disorder with a strong genetic component. The advent of whole exome sequencing (WES) has accelerated the discovery of genetic risk factors underlying familial disorders. OBJECTIVES: We set out to test whether damaging variants in known kidney disease genes explain a proportion of IgAN cases recruited in Ireland. METHODS: We performed WES in 10 Irish families with multiple affected members having kidney disease where at least one member had biopsy confirmed IgAN. Candidate variants were identified based on being shared between affected family members, minor allele frequency, function and predicted pathogenicity. Pathogenicity of variants was determined according to American College of Medical Genetics and Genomics guidelines. RESULTS: We detected candidate variants in 3 of 10 families. We identified a likely pathogenic variant in COL4A5 in one family and a variant of unknown significance (VUS) in COL4A3 in another. Variants in COL4A5 and COL4A3 are known to cause Alport syndrome. In the third family, we identified a VUS in LMX1B, a gene associated with Nail-patella syndrome. CONCLUSIONS: We identified a number of cases of familial IgAN where the families harbored variants in known kidney disease-related genes indicating that potentially a number of cases of familial IgAN are mistaken for other familial kidney disorders. However, the majority of families studied did not carry a candidate variant in a known kidney disease causing gene indicating that there may be >1 underlying genetic mechanism present in these families.

Images: Identification and Effect of Periodic Limb Movements in End-Stage Renal Disease.

None: Sleep disorders are prevalent in patients with end-stage renal disease (ESRD). In those patients on nocturnal dialysis, it is important to perform objective sleep assessment during regular dialysis. We present the case of a man on continuous cycler peritoneal dialysis with disabling fatigue and moderate restless legs syndrome (RLS). Actigraphy demonstrated excessive nocturnal movement. Unattended home polysomnography, performed during his regular peritoneal dialysis, confirmed frequent nocturnal periodic limb movements with disturbed sleep. Treatment with low dose pramipexole led to improved RLS and marked improvement in his energy. Clinicians caring for patients with ESRD should have a low threshold for objective sleep assessment given that sleep disorders are common, disabling and eminently amenable to treatment.

Assessing the discrimination of the Kidney Donor Risk Index/Kidney Donor Profile Index scores for allograft failure and estimated glomerular filtration rate in Ireland's National Kidney Transplant Programme.

BACKGROUND: The Kidney Donor Risk Index (KDRI)/Kidney Donor Profile Index (KDPI) is relied upon for donor organ allocation in the USA, based on its association with graft failure in time-to-event models. However, the KDRI/KDPI has not been extensively evaluated in terms of predictive metrics for graft failure and allograft estimated glomerular filtration rate (eGFR) outside of the USA. METHODS: We performed a retrospective analysis of outcomes in the Irish National Kidney Transplant Service Registry for the years 2006-13. Associations of the KDRI/KDPI score with eGFR at various time points over the follow-up and ultimate graft failure were modelled. RESULTS: A total of 772 patients had complete data regarding KDRI/KDPI calculation and 148 of these allografts failed over the follow-up. The median and 25-75th centile for KDRI/KDPI was 51 (26-75). On repeated-measures analysis with linear mixed effects models, the KDRI/KDPI (fixed effect covariate) associated with eGFR over 5 years: eGFR = -0.25 (standard error 0.02; P < 0.001). The variability in eGFR mathematically accounted for by the KDRI/KDPI score was only 21%. The KDRI/KDPI score did not add significantly to graft failure prediction above donor age alone (categorized as > and <50 years of age) when assessed by the categorical net reclassification index. CONCLUSIONS: In this cohort, while the KDRI/KDPI was predictive of eGFR over the follow-up, it did not provide additive discrimination above donor age alone in terms of graft failure prediction. Therefore it is unlikely to help inform decisions regarding kidney organ allocation in Ireland.

The impact of donor and recipient common clinical and genetic variation on estimated glomerular filtration rate in a European renal transplant population.

Genetic variation across the human leukocyte antigen loci is known to influence renal-transplant outcome. However, the impact of genetic variation beyond the human leukocyte antigen loci is less clear. We tested the association of common genetic variation and clinical characteristics, from both the donor and recipient, with posttransplant eGFR at different time-points, out to 5 years posttransplantation. We conducted GWAS meta-analyses across 10 844 donors and recipients from five European ancestry cohorts. We also analyzed the impact of polygenic risk scores (PRS), calculated using genetic variants associated with nontransplant eGFR, on posttransplant eGFR. PRS calculated using the recipient genotype alone, as well as combined donor and recipient genotypes were significantly associated with eGFR at 1-year posttransplant. Thirty-two percent of the variability in eGFR at 1-year posttransplant was explained by our model containing clinical covariates (including weights for death/graft-failure), principal components and combined donor-recipient PRS, with 0.3% contributed by the PRS. No individual genetic variant was significantly associated with eGFR posttransplant in the GWAS. This is the first study to examine PRS, composed of variants that impact kidney function in the general population, in a posttransplant context. Despite PRS being a significant predictor of eGFR posttransplant, the effect size of common genetic factors is limited compared to clinical variables.

A prototype line clamp for venous access bleeding in hemodialysis: A prospective cohort study.

INTRODUCTION: Venous needle dislodgement (or venous port disconnection) during hemodialysis (HD) may lead to catastrophic blood loss, particularly during unsupervised home HD. A prototype venous line clamp was developed for use in conjunction with the Redsense blood loss sensor. We hypothesize that this prototype device will provide additional safety to dialysis without excessive burden. METHODS: This was a single-center, prospective cohort study. Participants kept a log of bleeding, troubleshooting and clamp deployment events, and completed questionnaires before device first use and after device final use. The primary outcome was appropriate device function, evaluated by review of bleeding and clamp deployment events. The secondary outcomes were patient/nursing staff expectations and experience of the device. FINDINGS: Fourteen patients used the device during a combined total of 214 HD treatments. Five participants (36%) had experienced a bleeding or disconnection event prior to study recruitment. All vascular access types were represented. The device was tested during incenter HD (n = 7 patients) and home HD (n = 7 patients). There were eight clamp deployment events, three of which were in the setting of minor bleeding at the venous access site. No other bleeding events were reported. The main troubleshooting issues were related to cumbersome device connections. Participants perceived additional safety with the device (median score 4.25 out of 5; range 1-5). However, the amount of additional work created was variable, and large in some cases (median score 2 out of 5; range 0-4.5). There was no association between HD vintage and device burden (P = 0.55). DISCUSSION: This "proof of concept" study confirmed that a clamp on the venous line, operating in conjunction with a venous access blood detector, is feasible regardless of HD location or vascular access type. The device improved patient safety perception during HD but was burdensome. Design modifications could improve future device iterations.

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.

Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort.

Renal transplant recipients have an increased risk of non-melanoma skin cancer (NMSC) compared to in the general population. Here, we show polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of NMSC in a general, nontransplant setting, can predict risk of, and time to posttransplant skin cancer. Genetic variants, reaching predefined P-value thresholds were chosen from published squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) nontransplant GWAS. Using these GWAS, BCC and SCC PRS were calculated for each sample across three European ancestry renal transplant cohorts (n = 889) and tested as predictors of case:control status and time to NMSC posttransplant. BCC PRS calculated at P-value threshold 1 × 10-5 was the most significant predictor of case:control status of NMSC posttransplant (OR = 1.61; adjusted P = .0022; AUC [full model adjusted for clinical predictors and PRS] = 0.81). SCC PRS at P-value threshold 1 × 10-5 was the most significant predictor of time to posttransplant NMSC (adjusted P = 9.39 × 10-7 ; HR = 1.41, concordance [full model] = 0.74). PRS of nontransplant NMSC is predictive of case:control status and time to NMSC posttransplant. These results are relevant to how genomics can risk stratify patients to help develop personalized treatment regimens.