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Background and hypothesis: Kidney grafts from donors who died of stroke and related traits have worse outcomes relative to grafts from both living donors and those who died of other causes. We hypothesise that deceased donors, particularly those who died of stroke, have elevated polygenic burden for cerebrovascular traits. We further hypothesise that this donor polygenic burden is associated with inferior graft outcomes in the recipient. Methods: Using a dataset of 6666 deceased and living kidney donors from seven different European ancestry transplant cohorts, we investigated the role of polygenic burden for cerebrovascular traits (hypertension, stroke, and intracranial aneurysm (IA)) on donor age of death and recipient graft outcomes. Results: We found that kidney donors who died of stroke had elevated intracranial aneurysm and hypertension polygenic risk scores, compared to healthy controls and living donors. This burden was associated with age of death among donors who died of stroke. Increased donor polygenic risk for hypertension was associated with reduced long term graft survival (HR: 1.44, 95% CI [1.07, 1.93]) and increased burden for hypertension, and intracranial aneurysm was associated with reduced recipient estimated glomerular filtration rate (eGFR) at 1 year. Conclusions: Collectively, the results presented here demonstrate the impact of inherited factors associated with donors' death on long-term graft function. Graphical Abstract:

Defective DNA repair pathways contribute to the development of chronic kidney disease (CKD) in humans. However, the molecular mechanisms underlying DNA damage–induced CKD pathogenesis are not well understood. Here, we investigated the role of tubular cell DNA damage in the pathogenesis of CKD using mice in which the DNA repair protein Fan1 was knocked out. The phenotype of these mice is orthologous to the human DNA damage syndrome, karyomegalic interstitial nephritis (KIN). Inactivation of Fan1 in kidney proximal tubule cells sensitized the kidneys to genotoxic and obstructive injury characterized by replication stress and persistent DNA damage response activity. Accumulation of DNA damage in Fan1 tubular cells induced epithelial dedifferentiation and tubular injury. Characteristic to KIN, cells with chronic DNA damage failed to complete mitosis and underwent polyploidization. In vitroand in vivostudies showed that polyploidization was caused by the overexpression of DNA replication factors CDT1 and CDC6 in FAN1 deficient cells. Mechanistically, inhibiting DNA replication with Roscovitine reduced tubular injury, blocked the development of KIN and mitigated kidney function in these Fan1 knockout mice. Thus, our data delineate a mechanistic pathway by which persistent DNA damage in the kidney tubular cells leads to kidney injury and development of CKD. Furthermore, therapeutic modulation of cell cycle activity may provide an opportunity to mitigate the DNA damage response induced CKD progression.

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: PKD1and 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. Graphical abstract:

A brother and sister presented individually in their forties with progressive renal failure, bronchiectasis and mild derangements of their liver function tests. Both developed end-stage renal disease before the age of 50. Both siblings were found to carry a pathogenic, recessive, compound heterozygote mutation in the gene FAN1, which causes karyomegalic interstitial nephritis. Both siblings underwent renal transplantation. The sister developed small cell carcinoma of the lung 18 months after transplantation. Despite intensive chemotherapy she died 6 months later. Six years after transplant, the brother has developed prostate cancer and over 30 individual skin cancers. To our knowledge, only 6 other patients with FAN1mutations have undergone solid organ transplantation. Outcomes have been poor, with only 3 patients surviving beyond 1 year. While cancer is a significant risk for all patients in the post-transplant period, only 0.01% of patients develop >10 skin cancers. Transplantation may be an unrecognised risk in patients with FAN1mutations.

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 COL4A5in one family and a variant of unknown significance (VUS) in COL4A3in another. Variants in COL4A5and COL4A3are 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.

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.

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 eGFRat different time‐points, out to 5 years posttransplantation. We conducted GWASmeta‐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. PRScalculated using the recipient genotype alone, as well as combined donor and recipient genotypes were significantly associated with eGFRat 1‐year posttransplant. Thirty‐two percent of the variability in eGFRat 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 eGFRposttransplant 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 PRSbeing a significant predictor of eGFRposttransplant, the effect size of common genetic factors is limited compared to clinical variables. Polygenic risk score of nontransplant eGFR is a significant predictor of eGFR at 1 year posttransplant, but the effect size contributed by these common genetic variants is limited compared to that of clinical variables.

IMPORTANCE: Existing data suggest that nonmelanoma skin cancer (NMSC) is more common in renal transplant recipients than in maintenance dialysis patients. However, whether the risk of NMSC varies as the treatment modality for end-stage kidney disease (ESKD) changes between dialysis and transplantation is not well described. OBJECTIVE: To determine whether the incidence of NMSC is attenuated during periods of graft loss with a return to dialysis in those who receive multiple kidney transplants. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of data from recipients of kidney transplants from the Irish National Kidney Transplant Service database, linked with the Irish Cancer Registry, from 1994 to 2014. All analysis took place between January 10, 2018 and March 31, 2018. Standardized incidence ratios (SIRs) were calculated for NMSC incidence in comparison with the general population using Irish census data as the denominator. Incidence of NMSC was calculated with modality of treatment for ESKD varying over time; incidence rates and rate ratios associated with dialysis intervals were calculated using Poisson regression; and disease was defined according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for cancer diagnosis. EXPOSURES: Kidney transplantation. MAIN OUTCOMES AND MEASURES: Incidence rates per 1000 patient-years and incident rate ratios of NMSC after kidney transplant. RESULTS: Data from the records of 3821 deceased or living donor kidney transplant recipients were assessed; 2399 (62.8%) male and 1422 (37.2%) female recipients; mean (SD) age at time of first data recorded, 41.9 (16.0) years. A total of 3433 recipients were included who had a functioning transplant on January 1, 1994, or received a transplant after that date up to December 31, 2014: 3215 received 1 transplant, 522 a second kidney transplant, and 84 had 3 or more kidney transplants. Periods of treatment with a functioning transplant were associated with a higher incidence of NMSC diagnosis than periods of graft failure: adjusted incidence rate ratio (aIRR), 2.19 (95% CI, 1.56-3.07), P < .001. The aIRRs of NMSC fell from 41.7 (95% CI, 39.38-44.15) per 1000 patient-years in the first transplant to 19.29 (95% CI, 13.41-27.76) in the dialysis period following the first allograft failure. Incidence similarly rose and fell following each subsequent consecutive transplant. CONCLUSIONS AND RELEVANCE: In recipients of multiple kidney transplants, while the incidence of NMSC fell during periods defined by transplant failure, there was residual elevated risk. While ascertainment bias may have contributed to the observed trends, the stagnant incidence of invasive cancer overall highlights the need for continued cancer surveillance during graft failure.

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.

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 × 10−5was 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 × 10−5was 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. Polygenic risk score of nontransplant non‐melanoma skin cancer is predictive of case:control status and time to non‐melanoma posttransplant, demonstrating the use of genomics to stratify patients at risk for transplant complications.

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 × 10−5was 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 × 10−5was 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.

Background:IgA nephropathy is the most common primary glomerulonephritis worldwide and a significant cause of end-stage renal disease (ESRD). While most cases of IgA nephropathy are considered sporadic, familial cases have been reported. Methods:We performed a national audit of 1,809 patients attending renal clinics and dialysis units to identify a family history among patients with kidney disease. We reviewed all renal biopsies performed at our institution spanning a 30-year period. Paediatric cases were not included. Results:We identified 14 families involving 41 affected individuals with biopsy-proven IgA nephropathy and at least one other member with either biopsy-proven IgA nephropathy or ESRD. Detailed family histories were obtained, medical records reviewed and family pedigrees constructed. Retrospective application of the MESTC criteria to all familial IgA biopsies was performed. Seven families had 2 or more members with biopsy-proven IgA nephropathy, equating to 23 (1.8%) of 1,283 biopsies with IgA nephropathy over the last 30 years. A complex inheritance pattern was observed, with autosomal dominant and autosomal recessive families identified with varying penetrance. There was a male preponderance (68%), and a complex heterogeneity in the clinical and histopathological features of familial IgA patients (age range 16–60 years; creatinine range 60–350 μmol/L). We observed a high rate (66%) of progression to ESRD, with a mean time to progression of 5.13 years (SD 1.8 years; range 2–8 years). Among those patients who had undergone transplantation, recurrence of disease was reported in 5 (50%) cases. Conclusion:These data suggests familial aggregation of IgA nephropathy, confirm the clinical and histopathological heterogeneity and raise the possibility of monogenic inheritance.

Background Despite their well-recognised shortcomings, haemodialysis catheters (HDCs) remain an important form of haemodialysis access for many patients. There are several HDCs commercially available, each differing considerably in design, which is known to significantly influence performance and survival. We sought to determine which of two tunnelled HDCs, DuraMax®(Angiodynamics, NY, USA) or SplitCath®(MedComp, PA, USA) delivers the best performance, safety and reliability for dialysis patients.Methods Eighty-six patients were prospectively randomised to receive either DuraMax®(DM) or SplitCath®(SC). Outcomes included: (i) mean flow rates (mL/min) averaged over the first 10 weeks of dialysis, and urea reduction ratio (URR); and (ii) long-term catheter survival with appraisal of any events leading to catheter dysfunction and early removal.Results Median flow rates (interquartile range) in the DM and SC groups were 321 (309-343) and 309 (294-322) mL/min, respectively (p = 0.002). URR values for the DM and SC groups were 71 (65-76) and 74 (70-78), respectively, (p = 0.094). There was no significant difference in long-term survival or frequency of incidents that required early HDC removal (9/43 in the DM group, 5/43 patients SC). A slightly higher incidence of HDC dislodgement was noted in the DM group, although this study was not statistically powered to determine its significance.Conclusions We conclude that DM yields slightly higher flow rates in the first 10 weeks of dialysis, and a similar low incidence of complications and long-term survival for both DM and SC HDCs.

The authors reveal incidence and risk determinants of posttransplant lymphoproliferative disorders in Irish kidney transplant recipients as a national observational study. In their cohort, there is a paucity of early onset disease with no cases in the first year posttransplant.

Flow cytometric techniques are increasingly used in pretransplant crossmatching, although there remains debate regarding the clinical significance and predictive value of donor-specific antibodies detected by flow cytometry. At least some of the discrepancies between published studies may arise from differences in cutoffs used and lack of standardization of the test.

Delayed graft function (DGF) is a common complication in cadaveric kidney transplants affecting graft outcome. However, the incidence of DGF differs widely between centres as its definition is very variable. The purpose of this study was to define a parameter for DGF and immediate graft function (IGF) and to compare the graft outcome between these groups at our centre.

Prolonged cold ischaemic time (CIT) is associated with delayed initial graft function and may also have a nega-tive impact on long-term graft outcome. We carried out a study comparing the long-term graft survival rates between those recipients who received the first of a pair of donor kidneys versus the recipient of the second graft.

Prolonged cold ischaemic time (CIT) is associated with delayed initial graft function and may also have a negative impact on long-term graft outcome. We carried out a study comparing the long-term graft survival rates between those recipients who received the first of a pair of donor kidneys versus the recipient of the second graft.Adult kidney transplant recipients who received one of a pair of donor kidneys at our institution between 1989–1995 were included. All recipients received a cyclosporin based immunosupression regimen. Graft survival rates were compared between the 2 groups at 1-, 3-, 5- and 10-year intervals. A total of 520 renal transplant grafts were included in this study. Mean donor age was 35.4 years. Groups were similar for recipient age, gender, number of HLA mismatches, transplant number for that patient and percentage PRA. CIT was the only variable that was significantly different between the two groups; mean of 19.93 h in the first group compared to 25.65 h in the second group. Graft survival rates for the first kidney were significantly better than the second kidney—graft survival at 1 year 88.5% versus 84.7%, at 3 years 81.8% versus 76.7%, at 5 years 72.2% versus 64.9% and at 10 years 55.2% versus 40% (p = 0.012). Patient survival rates were similar in both groups.In our experience, the long-term graft survival rates are significantly better for the first kidney transplanted compared to the second kidney.

Accelerated acute humoral rejection (AHR) continues to occur in renal transplantation despite improved crossmatching, with potentially devastating consequences. Between 1 June 1998 and 31 December 2000, 440 renal transplants were performed in our center. AHR was diagnosed by the demonstration of typical pathological features on renal histology and positive direct immunofluorescence or detection of anti‐HLA antibodies in serum. AHR developed in 20 (4.5%) of our renal transplant recipients, nine male and eleven female at an average of 16.3 days post transplantation. All of these patients had a negative current cytotoxic crossmatch prior to transplantation. The median serum creatinine at diagnosis was 5.96 mg/dL, and 83% of these individuals developed oliguric renal failure requiring dialysis after having initially attained good graft function (median of best serum creatinine before AHR was 2.64 mg/dL). The 18 recipients who had not infarcted their grafts at the time of diagnosis of AHR received plasmapheresis in conjunction with intensification of their immunosuppressive regimen. This regimen was successful in reversing AHR in 78% of those treated with apheresis. In the 14 responders, graft survival at 6 months was 100% and at 12 months was 91%. Median serum creatinine at 6 and 12 months was 1.26 and 1.33 mg/dL, respectively. Patients received an average of 8.1 plasma exchanges. However, responders received a significantly higher frequency of plasmapheresis (P= .0053), despite undergoing a similar number of exchanges overall. Plasmapheresis appears to be an effective modality for reversing AHR and maintaining graft function. J. Clin. Apheresis 18:103–110, 2003. © 2003 Wiley‐Liss, Inc.

Accelerated acute humoral rejection (AHR) continues to occur in renal transplantation despite improved crossmatching, with potentially devastating consequences. Between 1 June 1998 and 31 December 2000, 440 renal transplants were performed in our center. AHR was diagnosed by the demonstration of typical pathological features on renal histology and positive direct immunofluorescence or detection of anti-HLA antibodies in serum. AHR developed in 20 (4.5%) of our renal transplant recipients, nine male and eleven female at an average of 16.3 days post transplantation. All of these patients had a negative current cytotoxic crossmatch prior to transplantation. The median serum creatinine at diagnosis was 5.96 mg/dL, and 83% of these individuals developed oliguric renal failure requiring dialysis after having initially attained good graft function (median of best serum creatinine before AHR was 2.64 mg/dL). The 18 recipients who had not infarcted their grafts at the time of diagnosis of AHR received plasmapheresis in conjunction with intensification of their immunosuppressive regimen. This regimen was successful in reversing AHR in 78% of those treated with apheresis. In the 14 responders, graft survival at 6 months was 100% and at 12 months was 91%. Median serum creatinine at 6 and 12 months was 1.26 and 1.33 mg/dL, respectively. Patients received an average of 8.1 plasma exchanges. However, responders received a significantly higher frequency of plasmapheresis (P = .0053), despite undergoing a similar number of exchanges overall. Plasmapheresis appears to be an effective modality for reversing AHR and maintaining graft function. J. Clin. Apheresis 18:103–110, 2003. © 2003 Wiley-Liss, Inc.

Renal dysfunction is a recognized complication of cardiac transplantation and can impact on the life expectancy of an already fragile population. A large proportion of these patients require transplantation because of the consequences of ischaemic heart disease (IHD) which, in turn, is often associated with ischaemic nephropathy. We studied the effect of IHD, diagnosed prior to transplantation, on the renal function of recipients who survived more than 6months after surgery. Of the 168 patients transplanted in a single centre over 15years, 132 were included in the study. Renal dysfunction was defined as a serum creatinine consistently above 200µmol/L (2.26mg/dL). Analysis confirmed that IHD was an independent risk factor for developing renal impairment. In transplant recipients with IHD, closer monitoring is warranted to detect and prevent renal dysfunction or to retard its progression.

Ultrasound dilution technology is emerging as the standard for measuring access recirculation and blood flow in hemodialysis patients. In temporary dialysis catheters, studies using the traditional two-needle urea method have suggested that short femoral catheters are associated with an unacceptably high degree of recirculation. This problem has never been assessed using ultrasound dilution technology. We performed a prospective observational study of consecutive patients undergoing dialysis through a temporary catheter. Measurements were made on 49 catheters; 10 catheters were excluded because poor flow necessitated reversal of the dialysis ports. Thirty-nine catheters in 33 patients were included in this analysis, of which 26 catheters were located in the femoral vein, and 13 catheters, in the internal jugular vein. Dialyzer blood flow was adjusted to give an ultrasonic flow rate of 250 mL/min (actual mean blood flow, 234.3 mL/min; 95% confidence interval [CI], 228 to 241). Overall mean recirculation rate was 8.9% (95% CI, 4.8 to 13.0). Multivariate analysis showed catheter location and length to be independent predictors of recirculation. Blood flow (within the range tested), duration into dialysis, time since catheter insertion, cardiac rhythm, and catheter type had no significant effect on recirculation rates. Recirculation in femoral catheters (13.1%) was significantly greater than that in internal jugular catheters (0.4%; P< 0.001). Femoral catheters shorter than 20 cm had significantly greater recirculation (26.3%) than those longer than 20 cm (8.3%; P= 0.007). We conclude that temporary femoral catheters shorter than 20 cm are associated with increased recirculation rates. In addition, when dialysis dose delivery is a priority, locating the temporary catheter in the internal jugular vein is an advantage.

Atherosclerotic renovascular disease (ARVD) continues to challenge the clinician as we enter the third millenium. ARVD frequently complicates patients with other vascular pathological states, and it is an increasingly common cause of end-stage renal failure. Although renovascular interventional procedures are now widely available and are of benefit to some patients with ARVD, a large proportion still progress to dialysis. Recent epidemiological investigations have emphasized the relationship between ARVD and other vascular diseases, and these are notable in patients with coronary artery disease and/or cardiac failure. Increased awareness of the possible coexistence of ARVD in patients with these latter conditions may allow earlier diagnosis and a minimization of complications (eg, angiotensin-converting enzyme inhibitor–related uremia or flash pulmonary edema). Contemporary studies also highlight the importance of intrarenal vascular and parenchymal injury in the cause of chronic renal failure in many patients with ARVD. Severe renal structural damage often coexists with proximal renal arterial narrowing, and this can explain the variability of renal functional outcomes known to accompany revascularization procedures. More appropriate selection of those patients likely to benefit from renovascular revascularization is now required. Large-scale trials that will identify the optimal approach to improving renal functional and survival outcomes in this high-risk group of patients are now long overdue.

Focal segmental glomerulosclerosis (FSGS) is a pathological entity characterized by proteinuria, nephrotic syndrome, and the progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD). Recently, familial forms of FSGS have been identified. Two families with autosomal dominant FSGS were evaluated for linkage using 351 genomic microsatellite markers. Linkage, multipoint analysis, and tests for heterogeneity were performed on the subsequent results. In addition, three small families were used for haplotype analysis. Evidence for linkage was found on chromosome 11q21–q22 for the largest family, with a maximum lod score of 9.89. The gene is currently localized to an 18-cM area between flanking markers D11S2002 and D11S1986. The disease in a second family was not linked to this locus or to a previously described locus on chromosome 19q13. There were no shared haplotypes among affected individuals in the three smaller families. Our findings demonstrate that genetic heterogeneity is prevalent in FSGS in that at least three genes cause the FSGS phenotype. Identification of the genes that cause familial FSGS will provide valuable insights into the molecular basis and pathophysiology of FSGS.

This article reviews the new trends in the diagnosis, treatment and prevention of catheter-related bacteraemia in clinical nephrology. Among these are the newer diagnostic techniques of evaluating and obtaining culture specimens from central lines, such as timed cultures and use of the endoluminal brush. In general, attempts to salvage infected haemodialysis lines are unsuccessful. We review the data that pertain to the use of antibiotic-coated catheters in non-dialysis patients and discuss how these observations may be applied to end-stage renal disease patients.

Focal segmental glomerulosclerosis (FSGS) has increasingly been recognized to occur in a familial pattern. We have observed the development of biopsy-confirmed FSGS and subsequent end-stage renal disease (ESRD) in one live related kidney donor and ESRD without biopsy in another. Both donors had family members with ESRD secondary to FSGS. Both donors were apparently healthy by routine physical examination, urinalysis, and serum creatinine at the time of evaluation as live related donors. We believe these cases emphasize the need for great caution when evaluating siblings as potential live related donors.

AbstractComplications due to ureteric obstruction are an occasional cause for renal transplant dysfunction. Here we report an unusual case of orthostatic renal failure in a renal transplant recipient. Our patient had the previously reported predisposing risk factors including: female sex, obesity, and lax abdominal musculature. It is important to recognize this unusual complication of renal transplantation early in order to preserve long‐term graft function.