Association between urinary sodium, creatinine, albumin, and long term survival in chronic kidney disease

Dietary sodium intake is associated with hypertension and cardiovascular risk in the general population. In patients with chronic kidney disease, sodium intake has been associated with progressive renal disease, but not independently of proteinuria. We studied the relationship between urinary sodium excretion and urinary sodium:creatinine ratio and mortality or requirement for renal replacement therapy in chronic kidney disease. Adults attending a renal clinic who had at least one 24-hour urinary sodium measurement were identified. 24-hour urinary sodium measures were collected and urinary sodium:creatinine ratio calculated. Time to renal replacement therapy or death was recorded. 423 patients were identified with mean estimated glomerular filtration rate of 48ml/min/1.73m<sup>2</sup>. 90 patients required renal replacement therapy and 102 patients died. Mean slope decline in estimated glomerular filtration rate was -2.8ml/min/1.73m<sup>2</sup>/year. Median follow-up was 8.5 years. Patients who died or required renal replacement therapy had significantly higher urinary sodium excretion and urinary sodium:creatinine but the association with these parameters and poor outcome was not independent of renal function, age and albuminuria. When stratified by albuminuria, urinary sodium:creatinine was a significant cumulative additional risk for mortality, even in patients with low level albuminuria. There was no association between low urinary sodium and risk, as observed in some studies. This study demonstrates an association between urinary sodium excretion and mortality in chronic kidney disease, with a cumulative relationship between sodium excretion, albuminuria and reduced survival. These data support reducing dietary sodium intake in chronic kidney disease but further study is required to determine the target sodium intake

Sources of Referral in Student Financial Counseling

This study evaluates sources of referral to financial counseling and varied declines in financial stress across the financial counseling process. College students came to counseling most often through self-referral. Younger students and women were more likely to respond to institutional referrals. There were two clearly discernable periods of decline in financial stress, smaller interim declines occurring after requesting appointments and larger declines that occurred in counseling sessions. The interim declines, however, were only operative for those who were self- or institutionally-referred and not for those who entered on a social-referral. A possible explanation is that social-referrals have already had “someone to talk to” whereas other referrals may only begin to feel a psychological burden lifted after making an appointment. Total declines in financial stress were mostly impervious to individual differences and sources of referral lending support to the notion that financial counseling itself contributed to aggregate declines in financial stress

Iridium‐Catalysed C−H Borylation of Fluoroarenes: Insights into the Balance between Steric and Electronic Control of Regioselectivity

The iridium catalysed C−H borylation of polyfluorinated arenes and heteroarenes occurs rapidly and efficiently. As with other borylation reactions, whilst steric parameters dominate, an underlying electronic influence on reaction selectivity can be observed. Notably borylation regioselectivity in fluorinated (hetero)arenes is determined by purely electronic effects except for ortho-borylation between two fluorine atoms where steric effects of fluorine substituents become apparent. Borylation at the para position with respect to fluorine is disfavoured whereas a strong electronic preference for borylation para to the azinyl nitrogen of pyridine is observed. When these features co-operate high selectivity can be expected. For these reactions, computations based on transition state, rather than intermediate, energies in iridium geometries showed excellent agreement between predicted and observed selectivities

Hematuria is associated with more severe acute tubulointerstitial nephritis

Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury. Although haematuria is a risk factor for the development of renal disease, no previous study has analyzed the significance of haematuria in ATIN. Retrospective, observational analysis of 110 patients with biopsy-proven ATIN was conducted. Results: Haematuria was present in 66 (60%) ATIN patients. A higher percentage of ATIN patients with haematuria had proteinuria than patients without haematuria (89.4% vs. 59.1%, p = 0.001) with significantly higher levels of proteinuria (median (interquartile range) protein:creatinine ratio 902.70 (513–1492) vs. 341.00 (177–734) mg/g, p <0.001). Moreover, those patients with more haematuria intensity had a higher urinary protein:creatinine ratio (1352.65 (665–2292) vs. 849.60 (562–1155) mg/g, p = 0.02). Those patients with higher proteinuria were more likely to need renal replacement therapy (22.7 vs. 0%, p = 0.03) and to su er relapse (4 vs. 0%, p = 0.03). At the end of follow up, haematuric ATIN patients had higher serum creatinine levels (3.19 2.91 vs. 1.91 1.17 mg/dL, p = 0.007), and a trend towards a higher need for acute dialysis (7 vs. 1%, p = 0.09) and renal replacement therapy (12.1 vs. 2.3%, p = 0.12). Haematuria is common in ATIN and it is associated with worse renal function outcomesSupported by FIS/FEDER PI17/00130 and PI19/00815, Spanish Ministry of Science and Innovation (RYC-2017-22369 and DTS18/00032), Sociedad Española de Nefrología, Fundacion Renal Iñigo Álvarez de Toledo (FRIAT), ISCIII-RETIC REDinREN RD016/0009 Fondos FEDER, Comunidad de Madrid B2017/BMD-3686CIFRA2-CM, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071)

Risk factors for bleeding complications after nephrologist-performed native renal biopsy

Background: Bleeding is a recognized complication of native percutaneous renal biopsy. This study aimed to describe the incidence of major bleeding after biopsy in a single centre over a 15-year period and examine factors associated with major bleeding. Methods: We identified consecutive adult patients undergoing ultrasound-guided native renal biopsy in the Glasgow Renal and Transplant Unit from 2000 to 2014. From the electronic patient record, we collected data pertaining to biopsy indication, pre- and post-biopsy laboratory measurements, prescribed medication and diagnosis. Aspirin was routinely continued. We defined major bleeding post-biopsy as the need for blood transfusion, surgical or radiological intervention or death. Binary logistic regression analysis was used to assess factors associated with increased risk of major bleeding. Results: There were 2563 patients who underwent native renal biopsy (1499 elective, 1064 emergency). The average age of patients was 57 (SD 17) years and 57.4% were male. Overall, the rate of major bleeding was 2.2%. In all, 46 patients required transfusion (1.8%), 9 patients underwent embolization (0.4%), no patient required nephrectomy and 1 patient died as a result of a significant late retroperitoneal bleed. Major bleeding was more common in those undergoing emergency compared with elective renal biopsy (3.4 versus 1.1%; P &lt; 0.001). Aspirin was being taken at the time of biopsy in 327 of 1509 patients, with no significant increase in the risk of major bleeding (P = 0.93). Body mass index (BMI) data were available for 546 patients, with no increased risk of major bleeding in 207 patients classified as obese (BMI &gt;30). Conclusions: The risk of major bleeding following native renal biopsy in the modern era is low. Complications are more common when biopsy is conducted as an emergency, which has implications for obtaining informed consent. Our data support the strategy of not stopping aspirin before renal biopsy

Generated randomly and selected functionally? The nature of enterovirus recombination

FA was supported by a PhD studentship from the Ministry of Education, Government of Saudi Arabia and KB was supported by Biological Sciences Research Council award BB/M009343/1to D.J.E and an ISSF award from The Wellcome Trust to the BSRC, University of St Andrews.Genetic recombination in RNA viruses is an important evolutionary mechanism. It con-tributes to population diversity, host/tissue adaptation and compromises vaccine efficacy. Both the molecular mechanism and initial products of recombination are relatively poorly understood. We used an established poliovirus-based in vitro recombination assay to investigate the roles of se-quence identity and RNA structure, both implicated or inferred from analysis of circulating recom-binant viruses, in the process. In addition, we used next generation sequencing to investigate the early products of recombination after cellular co-infection with different poliovirus serotypes. In independent studies we find no evidence for a role for RNA identity or structure in determining recombination junctions location. Instead, genome function and fitness are of greater importance in determining the identity of recombinant progeny. These studies provide further insights into this important evolutionary mechanism and emphasise the critical nature of the selection process on a mixed virus population.Publisher PDFPeer reviewe

Assessment of active tubulointerstitial nephritis in non-scarred renal cortex improves prediction of renal outcomes in patients with IgA nephropathy

Background: The addition of tubulointerstitial inflammation to the existing pathological classification of IgA nephropathy (IgAN) is appealing but was previously precluded due to reportedly wide inter-observer variability. We report a novel method to score percentage of non-atrophic renal cortex containing active tubulointerstitial inflammation (ATIN) in patients with IgAN and assess its utility to predict clinical outcomes. Methods: All adult patients with a native renal biopsy diagnosis of IgAN between 2010 and 2015 in a unit serving 1.5 million people were identified. Baseline characteristics, biopsy reports and outcome data were collected. ATIN was calculated by subtracting the percentage of atrophic cortex from the percentage of total cortex with tubulointerstitial inflammation, with ≥10% representing significant ATIN. The primary outcome was a composite of requiring renal replacement therapy or doubling of serum creatinine. Results: In total 153 new cases of IgAN were identified, of which 111 were eligible for inclusion. Of these, 76 (68%) were male and 54 (49%) had ATIN on biopsy. During a median follow-up of 2.3 years, 34 (31%) reached the primary outcome. On univariable Cox regression analysis, ATIN was associated with a five-fold increase in the primary outcome [hazard ratio (HR) (95% confidence interval) 4.9 (95% confidence interval (CI) 2.1–11.3)]. On multivariable analysis, mesangial hypercellularity, tubular atrophy and interstitial fibrosis and ATIN independently associated with renal outcome (P = 0.02 for ATIN). Inter-observer reproducibility revealed fair agreement in the diagnosis of ATIN (κ=0.43, P = 0.05). Conclusions: Within our centre, ATIN was significantly associated with renal outcome in patients with IgAN, independently of established histological features and baseline clinical characteristics

Obesity is not associated with progression to end stage renal disease in patients with biopsy-proven glomerular diseases

Background: Body mass index (BMI) is associated with renal disease progression in unspecified CKD. The relationship between BMI and primary glomerular disease (GN) may be more complex. We aimed to evaluate the association between BMI and renal disease progression in patients with primary glomerular disease (GN). Methods: This was a single-centre retrospective cohort study performed in adult patients with biopsy-proven primary GN (excluding minimal change disease) from January 2000 to December 2015, with follow-up data until June 2017. BMI at time of biopsy was categorised as ≤25 kg/m2, &gt; 25 to ≤30 kg/m2 and &gt; 30 kg/m2. We used univariate and multivariate survival analyses to evaluate factors associated with progression to a composite endpoint of stage 5 CKD or renal replacement therapy (Major Adverse Renal Event - MARE) censoring for competing risk of death using Fine and Gray subdistribution hazards model. Results: We included 560 patients with biopsy-proven primary GN and available BMI data: 66.1% were male with median age 54.8 (IQR 41.1–66.2) years and BMI 28.2 (IQR 24.9–32.1) kg/m2. Those with BMI 25-30 kg/m2 (n = 210) and with BMI &gt; 30 kg/m2 (n = 207) were older (p = 0.007) with higher systolic and diastolic blood pressures (p = 0.02 and 0.004 respectively) than those with BMI &lt; 25 kg/m2 (n = 132). There was a greater proportion of focal segmental glomerulosclerosis in those with higher BMI (3.9% in BMI &lt; 25 kg/m2, 7.9% in BMI 25–30 kg/m2 and 10.7% in BMI &gt; 30 kg/m2 of biopsies (p = 0.01)), but similar proportions of other GN diagnoses across BMI groups. Baseline eGFR (p = 0.40) and uPCR (p = 0.17) were similar across BMI groups. There was no interaction between BMI and time to MARE (log-rank p = 0.98) or death (log-rank p = 0.42). Censoring for competing risk of death, factors associated with progression to MARE were: younger age, lower baseline eGFR and higher uPCR, but not BMI (SHR 0.99, 95%CI 0.97–1.01, p = 0.31) nor blood pressure or GN diagnosis. Conclusion: BMI was not associated with progression to MARE in this patient cohort with primary GN. Efforts should be directed to managing other known risk factors for CKD progression