Low Urinary Creatinine Excretion Is Associated With Self-Reported Frailty in Patients With Advanced Chronic Kidney Disease.

INTRODUCTION: Frailty and muscle wasting, a component of frailty, are common in advanced stage chronic kidney disease (CKD). Whether frailty is associated with low urinary creatinine excretion (UCrE) as a measure of muscle mass in this population is unknown. Furthermore, reference values of UCrE are lacking. We first defined low UCrE and studied correlates of low UCrE, and subsequently studied cross-sectional associations of frailty with low UCrE in patients with advanced CKD. METHODS: A total of 2748 healthy individuals of the general population-based PREVEND study were included to define low UCrE (UCrE indexed for height, below the age- and sex-specific 5th percentile of the distribution). Frailty was defined using a modification of the Fried frailty phenotype. In a CKD population that included 320 and 967 participants of the PREPARE-2 and NECOSAD studies, respectively, cross-sectional associations of self-reported frailty, the individual components that define self-reported frailty, and frailty-associated variables with low UCrE were evaluated using multivariate logistic and linear regression models. RESULTS: Low UCrE was found in 38% of the CKD patients. A lower glomerular filtration rate was strongly associated with low UCrE. Self-reported frailty (adjusted odds ratio: 2.19; 95% confidence interval: 1.28-3.77) and the individual components were associated with low UCrE, independent of comorbidities. The frailty-associated variables hemoglobin and albumin were inversely associated with low UCrE, and parathyroid hormone was positively associated with low UCrE. DISCUSSION: Lower kidney function is a strong correlate of low UCrE and self-reported frailty, and the individual frailty components are associated with low UCrE as well, independent of comorbidities.

Pre-dialysis decline of measured glomerular filtration rate but not serum creatinine-based estimated glomerular filtration rate is a risk factor for mortality on dialysis.

Background: Monitoring of renal function is important in patients with chronic kidney disease progressing towards end-stage renal failure, both for timing the start of renal replacement therapy and for determining the prognosis on dialysis. Thus far, studies on associations between estimated glomerular filtration rate (eGFR) measurements in the pre-dialysis stage and mortality on dialysis have shown no or even inverse relations, which may result from the poor validity of serum creatinine-based estimation equations for renal function in pre-dialysis patients. As decline in renal function may be better reflected by the mean of the measured creatinine and urea clearance based on 24-h urine collections (mGFR by C Cr-U ), we hypothesize that in patients with low kidney function, a fast mGFR decline is a risk factor for mortality on dialysis, in contrast to a fast eGFR decline. Methods: For 197 individuals, included from the multicentre NECOSAD cohort, pre-dialysis annual decline of mGFR and eGFR was estimated with linear regression, and classified according to KDOQI as fast (>4 mL/min/1.73 m 2 /year) or slow (≤4 mL/min/1.73 m 2 /year). Cox regression was used to adjust for potential confounders. Results: Patients with a fast mGFR decline had an increased risk of mortality on dialysis: crude hazard ratio (HR) 1.84 (95% confidence interval: 1.13-2.98), adjusted HR 1.94 (1.11-3.36). In contrast, no association was found between a fast eGFR decline in the pre-dialysis phase and mortality on dialysis: crude HR 1.20 (0.75-1.89), adjusted HR 1.14 (0.67-1.94). Conclusions: This study demonstrates the importance of mGFR decline (by C Cr-U ) as opposed to eGFR decline in patients with low kidney function, and gives incentive for repeated mGFR measurements in patients on pre-dialysis care.

Timing of start of dialysis in diabetes mellitus patients: a systematic literature review.

BACKGROUND: Diabetes mellitus is a frequent cause of the need for renal replacement therapy (RRT). Historically, RRT was started earlier in patients with diabetes, in an attempt to prevent complications of uraemia and diabetes. We did a systematic review to find support for this earlier start of dialysis in patients with versus without diabetes. METHODS: The MEDLINE, EMBASE and CENTRAL databases were searched for articles about the timing of dialysis initiation in (subgroups of) patients with diabetes and CKD Stage 5. RESULTS: A total of 340 papers were screened and 11 papers were selected to be reviewed. Only three studies showed data of at least one subgroup of patients with diabetes. Two observational studies concluded that start of dialysis with a higher estimated glomerular filtration rate (eGFR) is beneficial with regard to survival, one did not find a difference and six observational studies concluded that start of dialysis with a lower eGFR is associated with better survival in patients with diabetes. The effect of timing of initiation of dialysis did not differ between patients with versus without diabetes. Lastly, one randomized controlled trial (two papers) reported that there was no difference in survival between start at higher versus lower eGFR overall and a P-value for the interaction with diabetes of P = 0.63, indicating no difference between patients with versus without diabetes with regard to the timing of start of dialysis and subsequent mortality on dialysis. CONCLUSIONS: There is no difference between early (eGFR) and late (lower eGFR) start of RRT with regard to mortality in patients with versus without diabetes. RRT should thus be initiated based on the same criteria in all patients, irrespective of the presence or absence of diabetes.

Uric acid is not associated with decline in renal function or time to renal replacement therapy initiation in a referred cohort of patients with Stage III, IV and V chronic kidney disease.

BACKGROUND: Although many studies have suggested an association between higher uric acid (UA) and both development of chronic kidney disease (CKD) and faster decline in renal function in Stage I and II CKD, it is not clear whether this effect is consistent throughout higher CKD stages. The aim of this study was to investigate the association between baseline UA and renal outcomes in patients with established CKD (Stages III-V). METHODS: We analysed data in the Swedish Renal Registry-Chronic Kidney Disease (SRR-CKD), which is a nationwide registry of referred CKD patients. Patients with a visit between January 1(st), 2005 and December 31(st), 2011 were followed until initiation of renal replacement therapy (RRT), death, referral to primary care or end of follow-up. Decline in renal function was assessed with a linear mixed model using all estimated glomerular filtration rate (eGFR) assessments recorded during median 28 months of follow-up, adjusting for important confounders such as demographic factors, primary renal disease, age, sex, relevant medication, diet, blood pressure and body mass index. RESULTS: There were 2466 patients with a baseline UA measurement {mean [standard deviation (SD)] of 7.81 [1.98] mg/dL}. The mean decline in renal function was -1.48 (95% CI -1.65; -1.31) mL/min/1.73 m(2) per year. The overall adjusted change in decline in renal function per unit increase in baseline UA was 0.08 (95% CI -0.01; 0.17) mL/min/1.73 m(2) per year indicating no association between higher UA levels and decline in renal function. In Stage III, IV and V CKD patients, the mean decline in renal function was -1.52 (95% CI -1.96; -1.08), -1.52 (95% CI -1.72; -1.32) and -1.19 (95% CI -1.75; -0.64) mL/min/1.73 m(2) per year, respectively. The adjusted change in the decline in renal function per unit increase in baseline UA was -0.09 (95% CI -0.30; 0.13) in Stage III CKD, 0.16 (95% CI 0.04; 0.28) in Stage IV CKD and 0.18 (95% CI -0.09; 0.45) in Stage V CKD. The overall adjusted hazard ratio for start of RRT was 0.97 (95% CI 0.93-1.02). For Stage III, IV and V CKD, it was 0.99 (95% CI 0.73-1.34), 0.97 (95% CI 0.91-1.03) and 0.99 (95% CI 0.91-1.07), respectively. CONCLUSION: UA is not associated with the rate of decline in renal function or time to start of RRT in Stage III, IV and/or V CKD patients.

Uric acid: association with rate of renal function decline and time until start of dialysis in incident pre-dialysis patients.

BACKGROUND: In patients with chronic kidney disease (CKD) hyperuricemia is common. Evidence that hyperuricemia might also play a causal role in vascular disease, hypertension and progression of CKD is accumulating. Therefore, we studied the association between baseline uric acid (UA) levels and the rate of decline in renal function and time until start of dialysis in pre-dialysis patients. METHODS: Data from the PREPARE-2 study were used. The PREPARE-2 study is an observational prospective cohort study including incident pre-dialysis patients with CKD stages IV-V in the years between 2004 and 2011. Patients were followed for a median of 14.9 months until start of dialysis, kidney transplantation, death, or censoring. Main outcomes were the change in the rate of decline in renal function (measured as estimated glomerular filtration rate (eGFR)) estimated using linear mixed models, and time until start of dialysis estimated using Cox proportional hazards models. RESULTS: In this analysis 131 patients were included with a baseline UA level (mean (standard deviation (SD)) of 8.0 (1.79) mg/dl) and a mean decline in renal function of -1.61 (95% confidence interval (CI), -2.01; -1.22) ml/min/1.73 m2/year. The change in decline in GFR associated with a unit increase in UA at baseline was -0.14 (95% CI -0.61;0.33, p=0.55) ml/min/1.73 m2/year. Adjusted for demography, comorbidities, diet, body mass index (BMI), blood pressure, lipids, proteinuria, diuretic and/or allopurinol usage the change in decline in eGFR did not change. The hazard ratio (HR) for starting dialysis for each mg/dl increase in UA at baseline was 1.08 (95% CI, 0.94;1.24, p=0.27). After adjustment for the same confounders the HR became significant at 1.26 (95% CI, 1.06;1.49, p=0.01), indicating an earlier start of dialysis with higher levels of UA. CONCLUSION: Although high UA levels are not associated with an accelerated decline in renal function, a high serum UA level in incident pre-dialysis patient is a risk factor for an earlier start of dialysis.

Surgical treatment of Neer type-II fractures of the distal clavicle: a meta-analysis.

BACKGROUND AND PURPOSE: Type-II distal clavicle fractures according to the Neer classification are generally operated because of the high non-union rate after non-operative treatment. Several surgical techniques have been developed in order to reduce the non-union rate and improve functional outcome. This meta-analysis overviews the available surgical techniques for type-II distal clavicular fractures. METHODS: We searched the literature systematically. No comparative studies were found. 21 studies (8 prospective and 13 retrospective cohort studies) were selected for the meta-analysis. Data were pooled for 5 surgical outcome measures: function, time to union, time to implant removal, major complications, and minor complications. RESULTS: The 21 studies selected included 350 patients with a distal clavicular fracture. Union was achieved in 98% of the patients. Functional outcome was similar between the treatment modalities. Hook-plate fixation was associated with an 11-fold increased risk of major complications compared to intramedullary fixation and a 24-fold increased risk compared to suture anchoring. INTERPRETATION: If surgical treatment of a distal clavicle fracture is considered, a fixation procedure with a low risk of complications and a high union rate such as plate fixation or intramedullary fixation should be used. The hook-plate fixation had an increased risk of implant-related complications.