Early and asymptomatic cardiac dysfunction in chronic kidney disease.

Background: Heart failure (HF) is highly prevalent and associated with high mortality in chronic kidney disease (CKD). However, the pathophysiology of cardiac dysfunction in CKD, especially in the early asymptomatic stage, is not well understood. We studied subclinical cardiac dysfunction in asymptomatic CKD patients without comorbid cardiac disease or diabetes mellitus by evaluating peak cardiac performance. Methods: In a cross-sectional study (n = 130) we investigated 70 male non-diabetic CKD patients (21 CKD stage 2-3a, 27 CKD stage 3b-4 and 22 CKD stage 5) employing specialized cardiopulmonary exercise testing to measure peak cardiac output and cardiac power output non-invasively. Data from 35 age-matched healthy male volunteers were obtained for comparison. In addition, as a positive control, data from 25 age-matched male HF patients in New York Heart Association class II and III were also obtained. Results: The study subjects showed a graded reduction in peak cardiac power, with 6.13 ± 1.11 W in controls, 5.02 ± 0.78 W in CKD 2-3a, 4.59 ± 0.53 W in CKD 3b-4 and 4.02 ± 0.73 W in CKD 5, although not as impaired as in HF, with 2.34 ± 0.63 W (all P < 0.005 versus control). The central haemodynamic characteristics of the cardiac impairment in CKD mirrored that of HF, with reduced flow and pressure-generating capacities, reduced chronotropic reserve and impaired contractility. Conclusions: The study demonstrates for the first time impaired peak cardiac performance and cardiac functional reserve in asymptomatic CKD patients. The evidence of myocardial dysfunction in the absence of comorbid cardiac disease and diabetes warrants further evaluation of current pathophysiological concepts of cardiovascular disease in CKD.

Phosphodiesterase Type 5 Inhibition Reduces Albuminuria in Subjects with Overt Diabetic Nephropathy.

Diabetic nephropathy (DN) is the leading cause of ESRD worldwide. Reduced bioavailability or uncoupling of nitric oxide in the kidney, leading to decreased intracellular levels of the nitric oxide pathway effector molecule cyclic guanosine monophosphate (cGMP), has been implicated in the progression of DN. Preclinical studies suggest that elevating the cGMP intracellular pool through inhibition of the cGMP-hydrolyzing enzyme phosphodiesterase type 5 (PDE5) might exert renoprotective effects in DN. To test this hypothesis, the novel, highly specific, and long-acting PDE5 inhibitor, PF-00489791, was assessed in a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel group trial of subjects with type 2 diabetes mellitus and overt nephropathy receiving angiotensin converting enzyme inhibitor or angiotensin receptor blocker background therapy. In total, 256 subjects with an eGFR between 25 and 60 ml/min per 1.73 m2 and macroalbuminuria defined by a urinary albumin-to-creatinine ratio >300 mg/g, were randomly assigned 3:1, respectively, to receive PF-00489791 (20 mg) or placebo orally, once daily for 12 weeks. Using the predefined primary assessment of efficacy (Bayesian analysis with informative prior), we observed a significant reduction in urinary albumin-to-creatinine ratio of 15.7% (ratio 0.843; 95% credible interval 0.73 to 0.98) in response to the 12-week treatment with PF-00489791 compared with placebo. PF-00489791 was safe and generally well tolerated in this patient population. Most common adverse events were mild in severity and included headache and upper gastrointestinal events. In conclusion, the safety and efficacy profile of PDE5 inhibitor PF-00489791 supports further investigation as a novel therapy to improve renal outcomes in DN.

Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker withdrawal in advanced renal disease: the STOP-ACEi trial.

BACKGROUND: Blood pressure (BP) control and reduction of urinary protein excretion using agents that block the renin-angiotensin aldosterone system are the mainstay of therapy for chronic kidney disease (CKD). Research has confirmed the benefits in mild CKD, but data on angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use in advanced CKD are lacking. In the STOP-ACEi trial, we aim to confirm preliminary findings which suggest that withdrawal of ACEi/ARB treatment can stabilize or even improve renal function in patients with advanced progressive CKD. METHODS: The STOP-ACEi trial (trial registration: current controlled trials, ISRCTN62869767) is an investigator-led multicentre open-label, randomized controlled clinical trial of 410 participants with advanced (Stage 4 or 5) progressive CKD receiving ACEi, ARBs or both. Patients will be randomized in a 1:1 ratio to either discontinue ACEi, ARB or combination of both (experimental arm) or continue ACEi, ARB or combination of both (control arm). Patients will be followed up at 3 monthly intervals for 3 years. The primary outcome measure is eGFR at 3 years. Secondary outcome measures include the number of renal events, participant quality of life and physical functioning, hospitalization rates, BP and laboratory measures, including serum cystatin-C. Safety will be assessed to ensure that withdrawal of these treatments does not cause excess harm or increase mortality or cardiovascular events such as heart failure, myocardial infarction or stroke. RESULTS: The rationale and trial design are presented here. The results of this trial will show whether discontinuation of ACEi/ARBs can improve or stabilize renal function in patients with advanced progressive CKD. It will show whether this simple intervention can improve laboratory and clinical outcomes, including progression to end-stage renal disease, without causing an increase in cardiovascular events.

The mortality and hospitalization rates associated with the long interdialytic gap in thrice-weekly hemodialysis patients.

Excess mortality and hospitalization have been identified after the 2-day gap in thrice-weekly hemodialysis patients compared with 1-day intervals, although findings vary internationally. Here we aimed to identify factors associated with mortality and hospitalization events in England using an incident cohort of 5864 hemodialysis patients from years 2002 to 2006 inclusive in the UK Renal Registry linked to hospitalization data. Higher admission rates were seen after the 2-day gap irrespective of whether thrice-weekly dialysis sequence commenced on a Monday or Tuesday (2.4 per year after the 2-day gap vs. 1.4 for the rest of the week, rate ratio 1.7). The greatest differences in admission rates were seen in patients admitted with fluid overload or with conditions associated with a high risk of fluid overload. Increased mortality following the 2-day gap was similarly independent of session pattern (20.5 vs. 16.7 per 100 patient years, rate ratio 1.22), with these increases being driven by out-of-hospital death (rate ratio 1.59 vs. 1.06 for in-hospital death). Non-white patients had an overall survival advantage, with the increased mortality after the 2-day gap being found only in whites. Thus, fluid overload may increase the risk of hospital admission after the 2-day gap and that the increased out-of-hospital mortality may relate to a higher incidence of sudden death. Future work should focus on exploring interventions in these subgroups.

Estimated albumin excretion rate versus urine albumin-creatinine ratio for the estimation of measured albumin excretion rate: derivation and validation of an estimated albumin excretion rate equation.

BACKGROUND: Glomerular filtration rate estimation equations use demographic variables to account for predicted differences in creatinine generation rate. In contrast, assessment of albuminuria from urine albumin-creatinine ratio (ACR) does not account for these demographic variables, potentially distorting albuminuria prevalence estimates and clinical decision making. STUDY DESIGN: Polynomial regression was used to derive an age-, sex-, and race-based equation for estimation of urine creatinine excretion rate, suitable for use in automated estimated albumin excretion rate (eAER) reporting. SETTING & PARTICIPANTS: The MDRD (Modification of Diet in Renal Disease) Study cohort (N=1,693) was used for equation derivation. Validation populations were the CRIC (Chronic Renal Insufficiency Cohort; N=3,645) and the DCCT (Diabetes Control and Complications Trial; N=1,179). INDEX TEST: eAER, calculated by multiplying ACR by estimated creatinine excretion rate, and ACR. REFERENCE TEST: Measured albumin excretion rate (mAER) from timed 24-hour urine collection. RESULTS: eAER estimated mAER more accurately than ACR; the percentages of CRIC participants with eAER within 15% and 30% of mAER were 33% and 60%, respectively, versus 24% and 39% for ACR. Equivalent proportions in DCCT were 52% and 86% versus 15% and 38%. The median bias of ACR was -20.1% and -37.5% in CRIC and DCCT, respectively, whereas that of eAER was +3.8% and -9.7%. Performance of eAER also was more consistent across age and sex categories than ACR. LIMITATIONS: Single timed urine specimens used for mAER, ACR, and eAER. CONCLUSIONS: Automated eAER reporting potentially is a useful approach to improve the accuracy and consistency of clinical albuminuria assessment.

Variation in centre-specific survival in patients starting renal replacement therapy in England is explained by enhanced comorbidity information from hospitalization data.

BACKGROUND: Unadjusted survival on renal replacement therapy (RRT) varies widely from centre to centre in England. Until now, missing data on case mix have made it impossible to determine whether this variation reflects genuine differences in the quality of care. Data linkage has the capacity to reduce missing data. METHODS: Modelling of survival using Cox proportional hazards of data returned to the UK Renal Registry on patients starting RRT for established renal failure in England. Data on ethnicity, socioeconomic status and comorbidity were obtained by linkage to the Hospital Episode Statistics database, using data from hospitalizations prior to starting RRT. RESULTS: Patients with missing data were reduced from 61 to 4%. The prevalence of comorbid conditions was remarkably similar across centres. When centre-specific survival was compared after adjustment solely for age, survival was below the 95% limit for 6 of 46 centres. The addition of variables into the multivariable model altered the number of centres that appeared to be 'outliers' with worse than expected survival as follows: ethnic origin four outliers, socioeconomic status eight outliers and year of the start of RRT four outliers. The addition of a combination of 16 comorbid conditions present at the start of RRT reduced the number of centres with worse than expected survival to one. CONCLUSIONS: Linked data between a national registry and hospital admission dramatically reduced missing data, and allowed us to show that nearly all the variation between English renal centres in 3-year survival on RRT was explained by demographic factors and by comorbidity.

Transplantation in the obese: separating myth from reality.

The prevalence of obesity among patients requiring renal replacement therapy continues to increase inexorably. While observational data have suggested that obesity may be associated with better outcomes among patients on dialysis, many centres have been reluctant to transplant obese patients because of concerns over adverse outcomes in the short and long term. In this review, we evaluate data about the safety of weight loss on dialysis and critically review the impact of pre-transplant body mass index and sarcopenia on post-transplant outcomes. We also highlight comparative data on outcomes of obese patients on dialysis versus those undergoing kidney transplantation. We conclude that while obesity can increase the risk of complications such as wound infections or delayed graft function, selected obese patients can achieve good outcomes after transplantation with the risk being broadly comparable to other recipient co-morbidities such as diabetes mellitus.

A study of the natural history of diabetic kidney disease (DKD).

BACKGROUND: In view of the alarming increase in the number of people with diabetes mellitus (DM), a rising number of patients with diabetic kidney disease (DKD), end-stage renal disease (ESRD) and cardiovascular disease (CVD) is forecasted. It is therefore imperative to re-visit the natural history of DKD and to identify potential risk factors, which may enhance the progression of the disease and its complications. METHODS: The medical records of 270 Type 2 diabetic chronic kidney disease patients followed up at the Sheffield Kidney Institute between 2000 and 2008 were reviewed. Various socio-demographic, clinical and biochemical parameters (baseline and follow-up parameters) were retrospectively collected from the patients' database. Progression of DKD was evaluated by evaluation of the rate of decline of estimated glomerular filtration rate (eGFR) as calculated from the simplified Modification of Diet in Renal Disease formula [progressors: loss of glomerular filtration rate (GFR) >2 mL/min/1.73m(2)/year] as well as by the progression pattern based on the slope of GFR changes. Variables associated with progression in univariate analysis were examined by multivariate analysis to determine the factors independently associated with DKD progression. RESULTS: The majority of the study populations were males (66.7%) and Caucasians (88%). Ninety-four patients (34.8%) had progressive, whereas 176 (65.2%) had non-progressive DKD. The rate of eGFR decline in progressors was -3.57 ± 1.45 mL/min/1.73m(2)/year compared to -1.31 ± 0.23 mL/min/1.73m(2)/year in non-progressors. The following parameters discriminated progressors from non-progressors by univariate analysis: baseline-blood pressure (BP) parameters, eGFR and proteinuria as well as serum uric acid. We also observed that area under the curve for follow-up systolic blood pressure (SBP), glycosylated haemoglobin (HbA1c) and proteinuria were significantly higher among the progressors (P = 0.043, P = 0.02 and P = 0.001, respectively). Independent determinants of DKD progression in this study in an adjusted logistic regression model were baseline HbA1c [odds ratio (OR), 2.27; 95% confidence interval (CI), 1.14-4.54], baseline SBP (OR, 1.23; 95% CI, 1.06-1.41), baseline proteinuria (OR, 3.24; 95% CI, 2.1-5.38), baseline serum uric acid (OR, 1.16; 95% CI, 1.09-1.39) and vascular co-morbidities (OR, 1.61; 95% CI, 1.02-2.54). Percentage changes in the key parameters (BP, HbA1c and proteinuria) during the first year of the study did not affect the rate of eGFR decline. CONCLUSIONS: Baseline HbA1c, SBP, proteinuria and serum uric acid together with the presence of vascular co-morbidities are strongly and independently associated with faster DKD progression. A further prospective observational study is currently undertaken to evaluate these findings and to determine the predictive value of other biochemical peptides and cellular markers on DKD outcome.

Do albuminuria and hs-CRP add to the International Diabetes Federation definition of the metabolic syndrome in predicting outcome?

BACKGROUND: To investigate the added value of elevated urinary albumin excretion (UAE) and high high-sensitive C-reactive protein (hs-CRP) in predicting new-onset type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD) and chronic kidney disease (CKD) in addition to the present metabolic syndrome (MetS) defining criteria. METHODS: The PREVEND Study is a prospective population-based cohort study in the Netherlands, including 8592 participants. The MetS was defined according to the 2004 International Diabetes Federation criteria, elevated UAE as albuminuria ≥ 30 mg/24 h and high hs-CRP as ≥ 3 mg/L. RESULTS: At follow-up, subjects without MetS when compared to subjects with MetS had a lower incidence of T2DM, CVD as well as CKD (2.5 versus 15.5; 4.1 versus 10.3 and 5.8 versus 11.2%, all P < 0.001). In subjects with MetS, the incidence of all three outcomes was higher among subjects with elevated albuminuria versus subjects with normoalbuminuria (all P < 0.01). The incidence of all outcomes was also higher among subjects with high hs-CRP versus subjects without elevated hs-CRP but only significant for CKD (P = 0.002). Multivariate analysis including elevated UAE, hs-CRP and the variables defining the MetS showed that elevated albuminuria was independently associated with the risk for new-onset T2DM, CVD and CKD, whereas high hs-CRP was only independently associated with new-onset CVD and CKD. CONCLUSION: Our data show that elevated UAE has added value to the present MetS defining variables in predicting new-onset T2DM, CVD and CKD, whereas hs-CRP adds to predicting new-onset CVD and CKD, but not T2DM.

Chapter 13 The linkage of incident renal replacement therapy patients in England (2002-2006) to hospital episodes and national mortality data: improved demography and hospitalisation data in patients undergoing renal replacement therapy.

INTRODUCTION: Missing data has hampered the comprehensive and inclusive reporting of adjusted outcomes for patients on renal replacement therapy (RRT) captured by the UK Renal Registry (UKRR). Furthermore the information collected by the UKRR does not currently include morbidity after starting RRT, details on hospital admission rates or location of death. Linking datasets offers the opportunity to enhance existing data and describe new measures of centre performance. METHODS: 21,633 incident patients, starting RRT between 2002 and 2006, were linked to all hospital care recorded by the Hospital Episode Statistics (HES) database and Office of National Statistics (ONS) mortality data using a secure anonymised service. Comorbidity prior to admission was determined from ICD10 coded HES admission diagnoses before the start of RRT, along with missing data on ethnicity and socioeconomic status. Location of death was determined by comparing the ONS and UKRR date of death to concurrent hospitalisations from HES. RESULTS: 290,443 admissions, 2.2 million haemodialysis attendances, 1.5 million outpatient attendances and 11,546 ONS deaths were returned for this cohort. Coding depth improved over time and varied between centres. Following linkage 21,271 patients were suitable for analysis, with improvements in ethnicity completeness (75.5% to 98.9%) and socioeconomic status (72.0% to 98.6%). Comorbidity improved substantially from 53.7% to 98.1% with 93% concordance in those with UKRR data. Mean comorbid scores between centres was similar (0.73-1.14) but variation in the proportion of admissions under nephrology in the first 12 months and the location of death between centres was noted, suggesting differing policies, practices and coding methods. CONCLUSIONS: Linking routine healthcare datasets with a national registry has dramatically reduced missing data and enables reporting of additional comprehensively adjusted measures of performance that allow more robust comparisons between centres. Hospitalisation frequency and associated mortality can be described in much greater detail. Linking routine datasets to national audits and registries represents an achievable, cost-effective and illuminating new way to evaluate services such as renal replacement therapy in the English NHS.

The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report.

The definition and classification for chronic kidney disease was proposed by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) in 2002 and endorsed by the Kidney Disease: Improving Global Outcomes (KDIGO) in 2004. This framework promoted increased attention to chronic kidney disease in clinical practice, research and public health, but has also generated debate. It was the position of KDIGO and KDOQI that the definition and classification should reflect patient prognosis and that an analysis of outcomes would answer key questions underlying the debate. KDIGO initiated a collaborative meta-analysis and sponsored a Controversies Conference in October 2009 to examine the relationship of estimated glomerular filtration rate (GFR) and albuminuria to mortality and kidney outcomes. On the basis of analyses in 45 cohorts that included 1,555,332 participants from general, high-risk, and kidney disease populations, conference attendees agreed to retain the current definition for chronic kidney disease of a GFR <60 ml/min per 1.73 m(2) or a urinary albumin-to-creatinine ratio >30 mg/g, and to modify the classification by adding albuminuria stage, subdivision of stage 3, and emphasizing clinical diagnosis. Prognosis could then be assigned based on the clinical diagnosis, stage, and other key factors relevant to specific outcomes. KDIGO has now convened a workgroup to develop a global clinical practice guideline for the definition, classification, and prognosis of chronic kidney disease.

Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts.

We studied here the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in individuals with chronic kidney disease (CKD). We performed a collaborative meta-analysis of 13 studies totaling 21,688 patients selected for CKD of diverse etiology. After adjustment for potential confounders and albuminuria, we found that a 15 ml/min per 1.73 m² lower eGFR below a threshold of 45 ml/min per 1.73 m² was significantly associated with mortality and ESRD (pooled hazard ratios (HRs) of 1.47 and 6.24, respectively). There was significant heterogeneity between studies for both HR estimates. After adjustment for risk factors and eGFR, an eightfold higher albumin- or protein-to-creatinine ratio was significantly associated with mortality (pooled HR 1.40) without evidence of significant heterogeneity and with ESRD (pooled HR 3.04), with significant heterogeneity between HR estimates. Lower eGFR and more severe albuminuria independently predict mortality and ESRD among individuals selected for CKD, with the associations stronger for ESRD than for mortality. Thus, these relationships are consistent with CKD stage classifications based on eGFR and suggest that albuminuria provides additional prognostic information among individuals with CKD.

Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts.

Screening for chronic kidney disease is recommended in people at high risk, but data on the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with all-cause and cardiovascular mortality are limited. To clarify this, we performed a collaborative meta-analysis of 10 cohorts with 266,975 patients selected because of increased risk for chronic kidney disease, defined as a history of hypertension, diabetes, or cardiovascular disease. Risk for all-cause mortality was not associated with eGFR between 60-105 ml/min per 1.73 m², but increased at lower levels. Hazard ratios at eGFRs of 60, 45, and 15 ml/min per 1.73 m² were 1.03, 1.38 and 3.11, respectively, compared to an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log risk for all-cause mortality without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 10, 30 and 300 mg/g were 1.08, 1.38, and 2.16, respectively compared to a ratio of five. Albuminuria and eGFR were multiplicatively associated with all-cause mortality, without evidence for interaction. Similar associations were observed for cardiovascular mortality. Findings in cohorts with dipstick data were generally comparable to those in cohorts measuring albumin-to-creatinine ratios. Thus, lower eGFR and higher albuminuria are risk factors for all-cause and cardiovascular mortality in high-risk populations, independent of each other and of cardiovascular risk factors.

OPPORTUNITY™: a large-scale randomized clinical trial of growth hormone in hemodialysis patients.

BACKGROUND: Adult maintenance hemodialysis (MHD) patients experience high mortality and morbidity and poor quality of life (QoL). Markers of protein-energy wasting are associated with these poor outcomes. The OPPORTUNITY™ Trial examined whether recombinant human growth hormone (hGH) reduces mortality in hypoalbuminemic MHD patients. Secondary end points were effects on number of hospitalizations, cardiovascular events, lean body mass (LBM), serum proteins, exercise capacity, QoL and adverse events. METHODS: We performed a randomized, double-blind, placebo-controlled, multicenter multinational trial stratified for diabetic status. Clinically, stable adult MHD patients with serum albumin <4.0 g/dL were randomized to subcutaneous injections of hGH, 20 µg/kg/day, or placebo. Planned treatment duration was 24 months for 2500 patients. The trial was terminated early due to slow recruitment. RESULTS: Seven hundred and twelve patients were randomized until trial termination; 695 patients received at least one dose of trial medication. Mean treatment duration was 20 weeks (no completers). There were no differences between groups in all-cause mortality, cardiovascular morbidity or mortality, serum albumin, LBM, physical exercise capacity or QoL. The hGH group, compared to placebo, displayed a reduction in body weight, total body fat, serum high-sensitivity C-reactive protein and possibly homocysteine and an increase in serum high-density lipoprotein-cholesterol and transferrin levels. CONCLUSIONS: Although the OPPORTUNITY™ Trial was terminated early, treatment with hGH, compared to placebo, improved certain cardiovascular risk factors but did not reduce mortality, cardiovascular events or improve nutritional factors or QoL. The power for showing differences was substantially reduced due to the marked decrease in treatment duration and sample size.

Microalbuminuria: marker or maker of cardiovascular disease.

Advancing age is associated with albuminuria and vascular changes. This review will explore the putative links between the two. Vascular ageing involves endothelial dysfunction as well as increased arterial diameter, wall thickness and stiffness, ultimately leading to arterial sclerosis. This process is accelerated by a defective vascular repair process. Endothelial dysfunction is likely to be involved in the initiation and development of microalbuminuria. It is often followed by the development and progression of atherosclerosis. Initially, microalbuminuria is reversible but becomes fixed with the progression of vascular structural changes including glomerulosclerosis. The prevalence of microalbuminuria increases with age and has been shown to be a marker of widespread microvasculopathy at various levels including cerebral, cardiac and renal microcirculations. This has been linked to endpoint clinical events, with microalbuminuria increasing the risk of cognitive impairment and strokes, cardiovascular disease outcomes, and progression to end-stage renal failure. Evidence of microvascular damage such as microalbuminuria associated with increased cardiovascular risk may suggest that microvascular damage and dysfunction predate overt macrovascular disease. Microalbuminuria and reduced glomerular filtration rate (GFR) may be markers of different pathologic processes. It is likely that microalbuminuria and reduced GFR simply represent, respectively, the spectrum of renal vascular manifestations from systemic endothelial dysfunction (microvascular disease) to systemic atherosclerosis (macrovascular disease).

Proteinuria thresholds are irrational: a call for proteinuria indexing.

Current guidelines for chronic kidney disease (CKD) diagnosis, referral and management are based on absolute thresholds of proteinuria/albuminuria with no reference to the residual nephron mass or function. This is illogical since the severity of proteinuria is a direct reflection of the number of filtering nephrons as well as their pathology and the capacity of the tubules to reabsorb filtered protein/albumin. The current simplistic approach to proteinuria may also compromise its usefulness as a robust guide to appropriate treatment, e.g. preferential use of inhibitors of the renin-angiotensin-aldosterone system. The routine measurement of the urinary protein/albumin:creatinine ratio (PCR/ACR) and estimated glomerular filtration rate (eGFR) gives rise to the opportunity to index proteinuria for renal function (i.e. a PCR:eGFR or ACR:eGFR ratio). Since both PCR/ACR and eGFR are reflections of quantities assessed per unit body surface area, this is a logical approach to the assessment of proteinuria/albuminuria. We advocate a consideration of the benefits of indexing PCR/ACR for eGFR to optimise treatment decisions based on proteinuria/albuminuria.

Stopping renin-angiotensin system inhibitors in chronic kidney disease: predictors of response.

BACKGROUND/AIMS: Renin-angiotensin system (RAS) inhibitors are considered first-line agents for hypertensive patients with progressive chronic kidney disease (CKD). In a previous study, we showed that stopping RAS inhibitors increased estimated glomerular filtration rate (eGFR) in a significant number of advanced CKD patients. The present study tries to address who would benefit and whether this benefit is predictable. METHODS: Forty-three CKD stage 4 patients had RAS inhibitors stopped and were followed for at least 24 months. Compared outcome groups were 'alive', 'renal replacement therapy (RRT)' or 'died'. Improvement in eGFR was used in a receiver-operating characteristic curve and finds the best predictor for surviving without RRT. RESULTS: Patients who survived without RRT were all hypertensive and had a higher eGFR increment after stopping the drugs. Those with eGFR improvement ≥5 ml/min/1.73 m(2) were the most likely to survive long term without RRT (log-rank test, p = 0.03). They had a significant increment in blood pressure that correlated with eGFR improvement (r = 0.403, p = 0.013). CONCLUSION: A significant increase in eGFR after stopping RAS inhibitors suggests that long-term survival without RRT is more likely. Our findings question the universal preemptive indication of RAS inhibitors in advanced CKD and suggest that they can be safely stopped, at least in some patients.

Cardio-Kidney-Damage: a unifying concept.

The perceived global rise in chronic kidney disease (CKD) has been met with apprehension and skepticism. It has been argued by some that we are facing a CKD 'epidemic' and by others that the high prevalence of CKD observed in different communities may be the result of flawed screening methods and tools. Both estimation of glomerular filtration rate and determination of microalbuminuria as markers of CKD have been criticized. Also, many commented that CKD, as currently defined, was primarily a disease of elderly people with reduced kidney function. Some described this as a physiological age-related decline in kidney function while others consider it to be pathological, warranting the label of a disease. In this review, an attempt is made to reconcile different views by examining some of the available evidence and to conclude that the high prevalence of 'CKD' in the elderly population is likely to reflect the underlying high prevalence of overt and subclinical atherosclerosis and cardiovascular disease. This leads to the conclusion that CKD is a reflection of diffuse and age-related Cardio-Kidney-Damage (C-K-D) that may not warrant the label of disease but certainly justifies attention with reduction of lifelong cardiovascular risks and careful evaluation and treatment.