Graham A. Stewart

Does Renal Dysfunction Predict Mortality After Acute Stroke? A 7-Year Follow-Up Study

Background and Purpose— The purpose of this study was to investigate renal function as a long-term predictor of mortality in patients hospitalized for acute stroke. Methods— This was a cohort study done in a Scottish tertiary teaching hospital. Participants included 2042 (993 male) unselected consecutive stroke patients (mean age, 73 years) admitted to hospital within 48 hours of stroke between1988 and 1994. Follow-up was up to 7 years. Main outcome measure was all-cause mortality. Results— The total number of deaths at the end of follow-up was 1026. Most subjects (1512) had creatinine <124 &mgr;mol/L. The mean calculated creatinine clearance was 54.8 mL/min (SD, 23 mL/min). Renal function indexes were analyzed by quartiles with Cox proportional-hazards model. Stroke survivors had higher calculated creatinine clearance and lower serum creatinine, urea, and ratios of urea to creatinine. Calculated creatinine clearance ≥51.27 mL/min significantly predicted better long-term survival in these stroke patients even after adjustment for confounders (age, neurological score, ischemic heart disease, hypertension, smoking, and diuretic use). Similarly, creatinine ≥119 &mgr;mol/L “relative risk (RR), 1.59; 95% confidence interval (CI), 1.32 to 1.92”, urea 6.8 to 8.9 mmol/L (RR, 1.34; 95% CI, 1.09 to 1.65) or ≥9 mmol/L (RR, 1.74; 95% CI, 1.42 to 2.13), and ratio of urea to creatinine ≥0.08573 mmol/&mgr;mol (RR, 1.24; 95% CI, 1.03 to 1.50) remained significant predictors of mortality after adjustment for confounders. Conclusions— After acute stroke, patients with reduced admission calculated creatinine clearance, raised serum creatinine and urea concentrations (even within conventional reference intervals), and raised ratio of urea to creatinine had a higher mortality risk. This finding may be used to stratify risk and target interventions, eg, the use of angiotensin-converting enzyme inhibitors.

Hypertension, antihypertensive agents and outcomes following renal transplantation.

Abstract:u2002 Hypertension is common following renal transplantation and adversely affects graft and patient survival. However, strategies for antihypertensive drug therapy and target blood pressure have not been clearly defined.

Determinants of hypertension and left ventricular function in end stage renal failure: a pilot study using cardiovascular magnetic resonance imaging

Cardiovascular disease is the principal cause of mortality in patients with renal failure. Left ventricular (LV) abnormalities are adverse prognostic indicators for cardiovascular outcome. The aim of this study was to use cardiac magnetic resonance scanning (CMR) to define LV functional abnormalities in haemodialysis (HD) patients and clarify the determinants of blood pressure (BP) and the effect of anaemia in this population. We studied 44 HD patients and 11 controls with CMR performed following dialysis. Forty patients and 11 controls completed the study. LV mass (P<0·001) and estimated systemic vascular resistance (SVR) (Pu2003=u20030·002) were significantly higher in the dialysis group compared to controls. LV ejection fraction (Pu2003=u20030·002) and SV (Pu2003=u20030·043) were lower than controls. In the HD patients, BP correlated significantly with cardiac output (CO; ru2003=u20030·569, P<0·001) and end diastolic volume (EDV; ru2003=u20030·565, P<0·001) but there was no correlation between BP and SVR (ru2003=u20030·201, Pu2003=u20030·594). Haemoglobin was inversely correlated with both CO (ru2003=u2003−0·531, P<0·001) and EDV (ru2003=u2003−0·493, Pu2003=u20030·001) and positively with SVR (ru2003=u20030·402, Pu2003=u20030·009). HD patients had a higher LV mass and lower ejection fraction than controls. The relationship of BP with CO, but not SVR, supports the theory that a major determinant of BP is intravascular volume and CO rather than vascular resistance although there was a fixed increase in SVR in this population. Improved understanding of the mechanisms underlying increased SVR and improved control of CO and intravascular volume may allow better therapeutic strategies. CMR provides insights into the pathophysiology of hypertension and LV dysfunction in HD patients.

Centre variation in incidence, indication and diagnosis of adult native renal biopsy in Scotland

BACKGROUNDnUK native renal biopsy incidence is unknown. Biopsy registries in other countries indicate that the incidence of renal biopsy varies widely. Indications for renal biopsy are largely opinion based.nnnMETHODSnThe Scottish Renal Biopsy Registry aimed to analyse the incidence of native renal biopsy in Scotland and examine indications and diagnoses obtained where practice varied widely.nnnRESULTSnConsecutive native adult renal biopsies performed in eight of the nine Scottish regions that include 82.4% of the population between 2002 and 2006 were examined. A total of 2480 native renal biopsies were performed equating 126.3 biopsies per million population per year (PMP/year). A total of 56.9% of patients were male, mean age 55.6 years (SD 1.3). The centres varied widely, from a lowest mean annual incidence of 65.8 PMP/year in Fife to the highest of 170.7 PMP/year in Tayside. The prospectively recorded indications and diagnoses were compared between Greater Glasgow, Clyde and Forth Valley (GC&FV) (population 1.56 million, 101.6 biopsies PMP/year) and Tayside (population 0.39 million, 177.4 biopsies PMP/year). Differing incidence of renal biopsy in these regions was mainly explained by patients with proteinuria and preserved renal function in the absence of nephrotic syndrome (19.2 PMP/year in GC&FV versus 60.8 PMP/year in Tayside), probably due to variation in nephrologists opinion about the utility of biopsy for this indication. Tayside diagnosed more primary glomerulopathies, diabetic nephropathy and chronic ischaemia than GC&FV.nnnCONCLUSIONSnWe have demonstrated wide regional variability in incidence of native renal biopsy within a single country, with analysis suggesting that this is mainly explained by uncertainty about the utility of renal biopsy for patients with proteinuria and preserved renal function. Further studies are required to determine the value of renal biopsy in this setting.

How safe is renal replacement therapy? A national study of mortality and adverse events contributing to the death of renal replacement therapy recipients

BACKGROUNDnPatients receiving treatment with renal replacement therapy (RRT) have high mortality, and ensuring patient safety in this population is difficult. We aimed to estimate the incidence and nature of medical adverse events contributing to the death of patients being treated with RRT.nnnMETHODSnThis population registry-based retrospective case review study included all patients being treated with RRT for established renal failure in Scotland and who died between 1 January 2008 and 30 June 2011. Deaths were reviewed by consultant nephrologists using a structured questionnaire to identify factors contributing to death occurring in both the inpatient and outpatient setting. Reviewers were able to use any information source deemed relevant, including paper and electronic clinical records, mortality and morbidity meetings and procurator fiscal (Scottish coroner) investigations. Deaths occurring in 2008 and 2009 where avoidable factors were identified that may have or did lead to death of a patient were subject to further review and root cause analysis, in order to identify recurrent themes.nnnRESULTSnOf 1551 deaths in the study period, 1357 were reviewed (87.5%). Cumulative RRT exposure in the cohort was 2.78 million person-days. RRT complications were the primary cause of death in 28 (2.1%). Health-care-associated infection had contributed to 9.6% of all deaths. In 3.5% of deaths, factors were identified which may have or did contribute to death. These were both organizational and human error related and were largely due to five main causes: management of hyperkalaemia, prescribing, out of hours care, infection and haemodialysis vascular access.nnnCONCLUSIONSnAdverse events contributing to death in RRT recipients mainly relate to the everyday management of common medical problems and not the technical aspects of RRT. Efforts to avoid harm in this population should address these ubiquitous causes of harm.

Kidney biopsy findings in primary Sjögren syndrome

BACKGROUNDnRenal involvement is rare in primary Sjögren syndrome (PSS). In this study, we examined renal biopsy findings in patients with PSS and correlated them with their clinical and renal findings.nnnMETHODSnTwenty-five patients with PSS who underwent renal biopsies from two renal units in Scotland between 1978 and 2013 were identified from renal biopsy database. We examined the renal morphologic, clinical and renal findings at the time of renal biopsy, renal and patient outcomes.nnnRESULTSnThe diagnosis of PSS preceded renal biopsy in 18/25 patients. In this group, the median duration of the disease was 5.5 years. Significant proteinuria, combined microscopic haematuria and proteinuria and reduced renal excretory function were found in 76, 56 and 84% of patients, respectively. The 3-year actuarial patient survival was significantly lower in patients with glomerulonephritis as compared with tubulointerstitial nephritis (66 versus 100%, P = 0.02). There was no difference in 3-year actuarial renal survival between these two groups (92 versus 92%, P = 1.0).nnnCONCLUSIONSnRenal biopsy is rare in PSS and often reveals diverse pathological findings. Glomerulonephritis, as compared with tubulointerstitial nephritis, is associated with higher early mortality. Further studies are needed to evaluate the utility of renal biopsy and its impact on disease management.

Multiple socio-economic deprivation and impact on survival in patients with primary glomerulonephritis

Background: The impact of multiple socio-economic deprivation on patient outcomes in primary renal diseases is unknown. We aimed to assess whether risk of death or requiring renal replacement therapy (RRT) in patients with primary glomerulonephritis (GN) was higher in patients living in an area of multiple socio-economic deprivation. Methods: Patients undergoing native renal biopsy between 2000 and 2014 were identified. Baseline demographics, postcode at time of biopsy, follow-up blood pressure, proteinuria and time to death or RRT were recorded. The Scottish Index of Multiple Deprivation (SIMD) is a multidimensional model used to measure deprivation based on postcode. Using SIMD, patients were separated into tertiles of deprivation. Results: A total of 797 patients were included, 64.2% were male with mean age of 54.1 (standard deviation 17.0) years. Median follow-up was 6.3 (interquartile range 3.7–9.4) years during which 174 patients required RRT and 185 patients died. Patients in the most deprived tertile of deprivation were significantly more likely to die than those in the least deprived tertile [hazard ratio (HR) 2.2, P u2009< u20090.001], independent of age, baseline serum creatinine and blood pressure. They were not more likely to require RRT (P u2009= u20090.22). The increased mortality risk in the most deprived tertile was not uniform across primary renal diseases, with the association being most marked in focal segmental glomerulosclerosis (HR 7.4) and IgA nephropathy (HR 2.7) and absent in membranous nephropathy. Conclusion: We have demonstrated a significant independent 2-fold increased risk of death in patients with primary GN who live in an area of multiple socio-economic deprivation at the time of diagnosis as compared with those living in less deprived areas.

An Open-Label Dose-Finding Study of Allopurinol to Target Defined Reduction in Urate Levels in Hemodialysis Patients

Allopurinol is a xanthine oxidase inhibitor mainly used to reduce circulating urate (also known as uric acid) levels. This helps to prevent recurrent urate crystal deposition in the form of gout.1 Gout is relatively common in patients with renal failure. Although routine dose reduction of allopurinol is recommended in the hemodialysis (HD) population this is not based on evidence from robust clinical trials.2 Guidelines generally recommend aiming to reduce urate levels by 50% to protect against future gout episodes.3 This study aimed to determine the optimal dose of allopurinol to achieve this in the HD population. Determining an optimal dose of allopurinol to use in the HD population will first help to guide clinicians in their treatment of their HD patients who develop gout. Second, patients with end-stage renal disease are at greatly increased risk of cardiovascular disease and death.4 Urate levels are known to be higher in the chronic kidney disease (CKD) population than in the general population.5 We know from large observational studies that increased urate levels are strongly associated with an increased cardiovascular risk, in both the general and CKD populations.6–9 In addition to its urate-lowering abilities, allopurinol itself has some specific properties that make it a potentially attractive drug to use in the HD population. Allopurinol has been shown to improve endothelial function in several population groups— including CKD patients—who are prone to endothelial dysfunction.10–12 In a large observational study the use of allopurinol was associated with reduced cardiovascular and all-cause mortality in patients undergoing HD who had no history of cardiovascular disease.13 In addition to this, allopurinol has also been demonstrated to regress left ventricular hypertrophy (LVH) in CKD, diabetic patients and in those with ischemic heart disease.10,11,14 Given that reduction in left ventricular mass is a common therapeutic target in the HD population,15–18 it is a natural question whether allopurinol might also regress LVH in this population. Until now this had not been investigated in a robust prospective clinical trial. We therefore designed a clinical trial to investigate this, the ALTERED (Does ALlopurinol regress lefT ventricular hypertrophy in End stage REnal Disease) study. This study looked to address this question through a multicenter randomized, placebo-controlled, double-blind trial of allopurinol. The primary outcome of the ALTERED study is change in left ventricular mass measured by cardiac magnetic resonance imaging at follow-up from baseline after 1 year of therapy. For the reasons described above, defining the optimal dose of allopurinol to use in this study was a priority. The first stage of the ALTERED study was therefore an open-label dose-escalation study to determine the