Jonathan G. Fox

Early Initiation of Dialysis Fails to Prolong Survival in Patients with End-Stage Renal Failure

ABSTRACT. There is a trend to start dialysis earlier in patients with chronic renal failure. Studies that suggest improved survival from earlier initiation of dialysis are flawed in that they have measured survival from start of dialysis rather than from a time point before dialysis, when patients have the same renal function. This flaw is termed lead-time bias. Using the electronic patient record at the renal unit of Glasgow Royal Infirmary, all patients were identified who had received dialysis for chronic renal failure and who had sufficient data to calculate the time point at which they reached an estimated creatinine clearance (eC Cr ) of 20 ml/min ( n = 275). This date was used to time survival. The patients were divided into early and late start groups by the median eC Cr for all patients at initiation of dialysis, which was 8.3 ml/min. There was no significant benefit in patient survival from earlier initiation of dialysis. A Cox proportional hazards model demonstrated a significant inverse relationship between eC Cr at start of dialysis and survival (hazard ratio, 1.1; P = 0.02), i.e. , patients who started dialysis with a lower eC Cr tended to survive longer. This relationship retained significance when gender, age, weight, presence of diabetes, mode of first dialysis, initial dialysis access, hemoglobin, serum albumin, blood leukocyte count, Wright/Khan index, and eC Cr at the start of dialysis were taken into account. This study fails to support a policy of earlier initiation of dialysis for patients with end-stage renal failure.

How to measure renal function in clinical practice.

The reliable measurement of renal excretory function is of great importance in clinical practice and in research. The introduction of routine reporting of estimated glomerular filtration rate and a new definition of chronic kidney disease has renewed interest in methods of measuring renal function. Coupled with this is the fact that several countries are moving towards population screening for renal impairment to try to reduce the associated increased cardiovascular risk. Accurate measurement is methodologically difficult so surrogate measures such as serum creatinine levels and prediction formulas (based on factors such as the patients age, sex, and serum creatinine level) are more commonly used in routine practice. We describe routine and more specialised methods of assessing renal function and discuss estimated glomerular filtration rate. The kidney has several interlinked functions (box). These depend on glomerular filtration rate, the unit measure of kidney function. Glomerular filtration rate can be defined as the volume of plasma cleared of an ideal substance per unit of time (usually expressed as ml/min). The ideal substance is one that is freely filtered at the glomerulus and neither secreted nor reabsorbed by the renal tubules. Creatinine is the closest to an ideal endogenous substance for measuring glomerular filtration rate.w1 Plasma creatinine is almost exclusively a product of the metabolism of creatine and phosphocreatine in skeletal muscle, although ingestion of meat may also contribute slightly.w2 w3 In patients with stable renal function, serum creatinine levels are usually constant, with variability daily of about only 8%.w4 w5 Creatinine is freely filtered at the glomerulus and is not reabsorbed, but up to 15% is actively secreted by the tubules.w6 In advanced renal failure, excretion of creatinine through the gastrointestinal tract increases.w7 Measuring the creatinine clearance using serum creatinine level and a timed urine collection gives an …

Is it necessary to stop antiplatelet agents before a native renal biopsy

BACKGROUND The practice of advising patients to stop antiplatelet agents before an elective renal biopsy is widespread. The aim of this study was to compare the rate of bleeding complications in two centres that have different policies regarding the ongoing use of antiplatelet agents in patients undergoing an elective renal biopsy. Neither centre routinely checks bleeding time before renal biopsy. A secondary aim, therefore, was to compare complication rates from this cohort with those reported in the literature where screening for prolonged bleeding time is standard practice. METHODS A retrospective study of 1120 biopsies performed by nephrologists under direct ultrasound guidance in the two renal units in Glasgow, Scotland (Jan 2000 to May 2007) was undertaken. Antiplatelet agents were stopped 5 days before biopsy in one centre but continued in the other. Bleeding time was not measured before biopsy and pro-coagulants were not routinely administered. Major bleeding was defined as the need for blood transfusion, surgical or radiological intervention. Minor bleeding was defined as an >or=1.0 g/dL fall in haemoglobin following biopsy without the need for transfusion or intervention. RESULTS Haemoglobin fell by >or=1.0 g/dL in 221 (19.7%) patients. There were 21 (1.9%) major bleeding complications. No patient died or required nephrectomy. Gender, advancing age or worse renal impairment was not associated with an increased likelihood of bleeding. Bleeding complications in 75 patients continuing antiplatelet agents were compared with those occurring in 60 patients whose antiplatelet agents were discontinued. Minor complications were commoner in the first group (31.0 versus 11.7%; P = 0.008), though there was no difference in the rate of major complications. CONCLUSIONS The risk of major bleeding following a native renal biopsy under ultrasound guidance is low. Stopping antiplatelet agents before biopsy was associated with a lower rate of minor complications but there was no difference in the rate of major complications. Complication rates compare favourably with other published series in which bleeding time was checked and corrected.

Fractional excretions of albumin and IgG are the best predictors of progression in primary glomerulonephritis

BACKGROUND Proteinuria is the most sensitive predictor of development of progressive renal insufficiency, with increasing focus on the composition of proteinuria, particularly high molecular weight proteins such as immunoglobulin G (IgG) (molecular weight 150 kDa). Differing methods of assessing excretion of proteinuria molecules have limited interpretation of results. We aimed to assess the utility of available indices of IgG, total proteinuria and albumin excretions as predictors of chronic kidney disease (CKD) progression in patients with primary glomerulonephritis. METHODS We recruited 97 patients with primary glomerulonephritis and measured 24-h urinary protein excretion, 24-h urinary albumin excretion, selectivity index, albumin:creatinine ratio, urinary IgG:creatinine ratio, fractional excretion of albumin (FE Alb) and fractional excretion of IgG (FE IgG) at baseline. The composite endpoint was developing stage 5 CKD, requiring RRT or death. Receiver operating characteristics curve analysis was used to assess the value of each measure in predicting outcome. From this analysis, high- and low-risk patient groups according to each measure were established. These were then tested using Kaplan-Meier and Cox survival analysis. RESULTS During a median follow-up of 7.07 years, 23 patients developed the primary endpoint. FE IgG and FE Alb were the most sensitive predictive tests. The hazard ratios (HR) of developing the primary endpoint using FE IgG [HR 37.1 (95% CI 8.6-158.8)] and FE Alb [HR 35.2 (95% CI 8.2-150.8)] cut-offs were double those using the other measures. CONCLUSIONS FE IgG and FE Alb are superior to conventional measures of proteinuria in predicting outcome in patients with primary glomerulonephritis, possibly because they are more accurate indicators of impairment of glomerular permselectivity. FE Alb should be used, in conjunction with other measures of proteinuria, in future studies of prediction of CKD progression.

Validation of the Toronto Formula to Predict Progression in IgA Nephropathy

Background/Aim: Predicting outcome in IgA nephropathy (IgAN) is difficult. The Toronto formula uses average mean arterial blood pressure and proteinuria during the first 2 years of follow-up (MAP0–2, UP0–2) to predict the subsequent slope of estimated creatinine clearance (eCrCl). We aimed to validate the Toronto formula in a Scottish cohort and test the hypothesis that adding the slope eCrCl over the first 2 years of follow-up (eCrCl0–2) would improve the predictive utility of a similar multivariate model. Methods: Adultsfrom our centre with biopsy-proven IgAN (n = 169) and at least 2 years of follow-up (median 129.4 months) were included. Clinical data were used to calculate MAP0–2,UP0–2,slope eCrCl0–2 and predicted slope eCrCl (using the Toronto formula). Results: There was a significant correlation between predicted slope eCrCl using the Toronto formula and actual slope eCrCl (R2 = 0.21; p < 0.001). The formula predicted the actual rate of progression to within 4 ml/min/year in 75% of subjects, predicting patients with the most rapid deterioration with the greatest accuracy. The multivariate linear regression model created in our cohort using the same independent variables as the Toronto formula to predict the overall slope eCrCl had an R2 of 0.22 (p < 0.001) and adding the slope CrCl0–2 only increased this to 0.25. Conclusions: The Toronto formula is valid in a European population and useful for identifying patients at high risk of future deterioration in renal function. Adding slope eCrCl0–2 to a predictive model containing MAP0–2, andUP0–2 does not appear to improve prediction of the overall slope of eCrCl.

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 (UNa) excretion and UNa to creatinine ratio and mortality or requirement for renal replacement therapy in chronic kidney disease. Adult patients attending a renal clinic who had ≥1 24-hour UNa measurement were identified. Twenty-four-hour UNa measures were collected and UNa to creatinine ratio calculated. Time to renal replacement therapy or death was recorded. Four hundred twenty-three patients were identified with mean estimated glomerular filtration rate of 48 mL/min per 1.73 m2. Ninety patients required renal replacement therapy and 102 patients died. Mean slope decline in estimated glomerular filtration rate was −2.8 mL/min per 1.73 m2 per year. Median follow-up was 8.5 years. Patients who died or required renal replacement therapy had significantly higher UNa excretion and UNa to creatinine ratio, but the association with these parameters and poor outcome was not independent of renal function, age, and albuminuria. When stratified by albuminuria, UNa to creatinine ratio was a significant cumulative additional risk for mortality, even in patients with low-level albuminuria. There was no association between low UNa and risk, as observed in some studies. This study demonstrates an association between UNa 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 additional study is required to determine the target sodium intake.

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

BACKGROUND Patients 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. METHODS This 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. RESULTS Of 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. CONCLUSIONS Adverse 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.

Deceased donor transplantation in the elderly—are we creating false hope?

BACKGROUND Increasing numbers of older patients are developing established renal failure and considering kidney transplant as a renal replacement therapy (RRT) option. The probability of older patients actually receiving a deceased donor kidney transplant is unclear, preventing informed choice about pursuing the option of transplantation. We sought to analyse our RRT population to determine the probability of receiving a deceased donor kidney transplant in patients commencing RRT categorized by age and for whom there was no suitable living kidney donor. METHODS Patients commencing dialysis in our centre between 1992 and 2009 were identified. Time to listing on the deceased donor transplant waiting list and time to first deceased donor transplant were determined by Kaplan-Meier analysis for patients, categorized by age, with censoring at the date of first living donor kidney transplant, death or last dialysis. RESULTS One-thousand-five-hundred-and-thirteen patients were categorized into groups by age in years [1: <35 (n = 134), 2: 35-49.9 (n = 207), 3: 50-64.9 (n = 415), 4: >65-74.9 (n = 438) and 5: ≥ 75 (n = 319)]. The probability of being listed for deceased donor transplant within 1 year of commencing RRT was 75, 54, 27, 4 and 0.8% in Groups 1-5, respectively. If listed, the probability of receiving a deceased donor transplant within 5 years of starting RRT was 81, 48, 26, 8 and 0% in Groups 1-5, respectively. In Groups 1-4, 93% (n = 63), 87% (n = 65), 76% (n = 45) and 100% (n = 7) of the patients, respectively, who received a deceased donor transplant were alive and off dialysis 1 year after transplant. The reason patients who were listed did not receive a transplant was usually death on the waiting list. CONCLUSIONS The likelihood of being listed for transplant falls with increasing age at the time of starting RRT. Even for patients listed for transplant, the probability of older patients actually receiving a transplant is much lower than for younger patients, with only 8% of listed patients aged 65-74.9 years being transplanted within 5 years. This is partly the result of death on the waiting list but may also be related to organ allocation policies. Assessment for possible deceased donor transplantation involves a considerable investment in time and effort for the patient, as well as in health care resources, and a patients decision whether to proceed with assessment should be informed by the kind of information we have produced. As there may be regional and national variations in practice, each centre should generate such data for use locally.

The incidence of biopsy-proven IgA nephropathy is associated with multiple socioeconomic deprivation.

Chronic kidney disease is more common in areas of socioeconomic deprivation, but the relationship with the incidence and diagnosis of biopsy-proven renal disease is unknown. In order to study this, all consecutive adult patients undergoing renal biopsy in West and Central Scotland over an 11-year period were prospectively analyzed for demographics, indication, and histologic diagnosis. Using the Scottish Index of Multiple Deprivation, 1555 eligible patients were separated into quintiles of socioeconomic deprivation according to postcode. Patients in the most deprived quintile were significantly more likely to undergo biopsy compared with patients from less deprived areas (109.5 compared to 95.9 per million population/year). Biopsy indications were significantly more likely to be nephrotic syndrome, or significant proteinuria without renal impairment. Patients in the most deprived quintile were significantly more likely to have glomerulonephritis. There was a significant twofold increase in the diagnosis of IgA nephropathy in the patients residing in the most compared with the least deprived postcodes not explained by the demographics of the underlying population. Thus, patients from areas of socioeconomic deprivation in West and Central Scotland are significantly more likely to undergo native renal biopsy and have a higher prevalence of IgA nephropathy.

Predictors of sustained arteriovenous access use for haemodialysis.

Background: Guidelines encourage early arteriovenous (AV) fistula (AVF) planning for haemodialysis (HD). The aim of this study was to estimate the likelihood of sustained AV access use taking into account age, sex, comorbidity, anatomical site of first AVF and, for pre-dialysis patients, eGFR and proteinuria. Methods: 1,092 patients attending our centre who had AVF as their first AV access procedure between January 1, 2000 and August 23, 2012 were identified from the electronic patient record. The primary end-point was time to first sustained AV access use, defined as use of any AV access for a minimum of 30 consecutive HD sessions. Results: 52.9% (n = 578) of the patients ultimately achieved sustained AV access use. The main reasons for AV access non-use were AVF failure to mature and death. The 3-year Kaplan-Meier probability of sustained AV access use was 68.8% for those not on renal replacement therapy (RRT) (n = 688) and 74.2% for those already on RRT (n = 404) at the time of first AVF. By multivariate analysis in patients not on RRT, male sex (HR 2.22; p < 0.001), uPCR (HR 1.03; p = 0.03) and eGFR (hazard ratio, HR 0.85; p < 0.001) were independent predictors of AV access use. In patients already on RRT, age (HR 0.98; p < 0.001) and peripheral vascular disease (HR 0.48; p = 0.02) were independent predictors of AV access use. Conclusion: Our data suggest that refinement of the current guideline for timing of AV access creation in planning RRT is justified to take into account individual factors that contribute to the likelihood of technical success and clinical need.