Oxidative stress is a key player in the genesis and worsening of diabetic kidney disease (DKD). We aimed at collecting all available information on possible benefits of chronic antioxidant ...supplementations on DKD progression.
Systematic review and meta-analysis.
Adults with DKD (either secondary to type 1 or 2 diabetes mellitus).
Cochrane CENTRAL, Ovid-MEDLINE and PubMed were searched for randomized controlled trials (RCTs) or quasi-RCTs without language or follow-up restriction.
Any antioxidant supplementation (including but not limited to vitamin A, vitamin C, vitamin E, selenium, zinc, methionine or ubiquinone) alone or in combination.
Primary outcome was progression to end-stage kidney disease (ESKD). Secondary outcomes were change in albuminuria, proteinuria, serum creatinine and renal function.
From 13519 potentially relevant citations retrieved, 15 articles referring to 14 full studies (4345 participants) met the inclusion criteria. Antioxidant treatment significantly decreased albuminuria as compared to control (8 studies, 327 participants; SMD: -0.47; 95% CI -0.78, -0.16) but had apparently no tangible effects on renal function (GFR) (3 studies, 85 participants; MD -0.12 ml/min/1.73m2; 95% CI -0.06, 0.01). Evidence of benefits on the other outcomes of interest was inconclusive or lacking.
Small sample size and limited number of studies. Scarce information available on hard endpoints (ESKD). High heterogeneity among studies with respect to DKD severity, type and duration of antioxidant therapy.
In DKD patients, antioxidants may improve early renal damage. Future studies targeting hard endpoints and with longer follow-up and larger sample size are needed to confirm the usefulness of these agents for retarding DKD progression.
ObjectivesWhile increasing attention is paid to the rising prevalence of chronic diseases in Africa, there is little focus on chronic kidney disease (CKD). This systematic review assesses CKD burden ...among the general population and high-risk groups on the entire African continent.Design, setting and participantsWe searched Medline and PubMed databases for articles published between 1 January 1995 and 7 April 2017 by sensitive search strategies focusing on CKD surveys at the community level and high-risk groups. In total, 7918 references were evaluated, of which 7766 articles were excluded because they did not meet the inclusion criteria. Thus, 152 studies were included in the final analysis.Outcome measurementThe prevalence of CKD in each study group was expressed as a range and pooled prevalence rate of CKD was calculated as a point estimate and 95% CI. No meta-analysis was done. Data were presented for different populations.ResultsIn the community-level studies, based on available medium-quality and high-quality studies, the prevalence of CKD ranged from 2% to 41% (pooled prevalence: 10.1%; 95% CI 9.8% to 10.5%). The prevalence of CKD in the high-risk groups ranged from 1% to 46% (pooled prevalence: 5.6%; 95% CI 5.4% to 5.8%) in patients with HIV (based on available medium-quality and high-quality studies), 11%–90% (pooled prevalence: 24.7%; 95% CI 23.6% to 25.7%) in patients with diabetes (based on all available studies which are of low quality except four of medium quality) and 13%–51% (pooled prevalence: 34.5%; 95 % CI 34.04% to 36%) in patients with hypertension (based on all available studies which are of low quality except two of medium quality).ConclusionIn Africa, CKD is a public health problem, mainly attributed to high-risk conditions as hypertension and diabetes. The poor data quality restricts the validity of the findings and draws the attention to the importance of designing future robust studies.
Previous studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, ...multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control;
=145) or walking exercise (
=151); 227 patients (exercise
=104; control
=123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance±SD: baseline, 328±96 m; 6 months, 367±113 m) but not in the control group (baseline, 321±107 m; 6 months, 324±116 m;
<0.001 between groups). Similarly, the five times sit-to-stand test time improved in the exercise group (mean time±SD: baseline, 20.5±6.0 seconds; 6 months, 18.2±5.7 seconds) but not in the control group (baseline, 20.9±5.8 seconds; 6 months, 20.2±6.4 seconds;
=0.001 between groups). The cognitive function score (
=0.04) and quality of social interaction score (
=0.01) in the kidney disease component of the KDQOL-SF improved significantly in the exercise arm compared with the control arm. Hence, a simple, personalized, home-based, low-intensity exercise program managed by dialysis staff may improve physical performance and quality of life in patients on dialysis.
The Cox model is a regression technique for performing survival analyses in epidemiological and clinical research. This model estimates the hazard ratio (HR) of a given endpoint associated with a ...specific risk factor, which can be either a continuous variable like age and C-reactive protein level or a categorical variable like gender and diabetes mellitus. When the risk factor is a continuous variable, the Cox model provides the HR of the study endpoint associated with a predefined unit of increase in the independent variable (e.g., for every 1-year increase in age, 2 mg/L increase in C-reactive protein). A fundamental assumption underlying the application of the Cox model is proportional hazards; in other words, the effects of different variables on survival are constant over time and additive over a particular scale. The Cox regression model, when applied to etiological studies, also allows an adjustment for potential confounders; in an exposure-outcome pathway, a confounder is a variable which is associated with the exposure, is not an effect of the exposure, does not lie in the causal pathway between the exposure and the outcome, and represents a risk factor for the outcome.
In the EXerCise Introduction to Enhance Performance in Dialysis (EXCITE) trial, a simple, personalized 6-month walking exercise program at home during the day off of dialysis improved the functional ...status and the risk for hospitalization in patients with kidney failure. In this post-trial observational study, we tested whether the same intervention was associated with a lower long-term risk of death or hospitalization (combined end point) during a follow-up extended up to 36 months.
In total, 227 patients (exercise,
=104; control,
=123) completed the 6-month trial and entered the post-trial observational study. Data were analyzed by unadjusted and adjusted Cox regression analyses and Bayesian analysis.
In the long-term observation (up to 36 months), 134 events were recorded (eight deaths not preceded by hospitalization and 126 hospitalizations, which were followed by death in 38 cases). The long-term risk for hospitalization or death was 29% lower (hazard ratio, 0.71; 95% confidence interval, 0.50 to 1.00), and in an analysis stratified by adherence to the walking exercise program during the 6-month trial, the subgroup with high adherence (>60% of prescribed sessions) had a 45% lower risk as compared with the control group (hazard ratio, 0.55; 95% confidence interval, 0.35 to 0.87). A Bayesian analysis showed that the posterior probability of a hazard ratio of 0.71 (95% confidence interval, 0.50 to 1.00) for the risk of the composite outcome observed in the post-trial observational study was 93% under the conservative prior and 97% under the optimistic prior. Sensitivity analyses restricted to the risk of hospitalization only or censoring patients at the time of transplantation fully confirmed these findings.
A simple, personalized, home-based, low-intensity exercise program was associated with a lower risk of hospitalization.
EXerCise Introduction to Enhance Performance in Dialysis (EXCITE), NCT01255969.
Muscle sympathetic nerve activity (MSNA) has shown that sympathetic activation may occur in essential hypertension (EHT). However, the small sample size of the studies, the heterogeneity of the ...patients examined, and the presence of confounders represented major weaknesses not allowing to draw definite conclusions. Among the 432 studies identified providing information in EHT on MSNA, 63 were eligible (1216 patients) and meta-analyzed grouping them on the basis of clinically relevant questions(1) Is MSNA increased in hypertension of mild/moderate-to-severe degree? (2) Does sympathetic activation occur in borderline, white-coat, and masked EHT? (3) Is MSNA related to clinic and ambulatory blood pressure and target organ damage? (4) Are heart rate and venous plasma norepinephrine valuable surrogate markers of MSNA in clinical practice? The results show that MSNA was significantly greater (1.5×; P<0.001) in mild-to-moderate and severe EHT as compared with normotensive controls and that this was the case also in borderline, white-coat, and masked hypertension as well. Interestingly, MSNA was significantly greater in both untreated and treated hypertension (P<0.001 for both), related to clinic and ambulatory blood pressure (r=0.67 and r=0.83; P<0.001 for both), inversely related to heart rate (r=−0.38; P<0.001) and directly to venous plasma norepinephrine (r=0.28; P<0.001) and left ventricular mass index (r=0.27; P<0.001). Thus, EHT is a condition characterized by a sustained sympathetic overdrive, whose magnitude is proportional to its clinical severity. This is more clearly manifest when MSNA rather than indirect markers of adrenergic drive, such as heart rate and plasma norepinephrine, are used.
Studies performed in the field of oxidative medicine and cellular longevity frequently focus on the association between biomarkers of cellular and molecular mechanisms of oxidative stress as well as ...of aging, immune function, and vascular biology with specific time to event data, such as mortality and organ failure. Indeed, time-to-event analysis is one of the most important methodologies used in clinical and epidemiological research to address etiological and prognostic hypotheses. Survival data require adequate methods of analyses. Among these, the Kaplan-Meier analysis is the most used one in both observational and interventional studies. In this paper, we describe the mathematical background of this technique and the concept of censoring (right censoring, interval censoring, and left censoring) and report some examples demonstrating how to construct a Kaplan-Meier survival curve and how to apply this method to provide an answer to specific research questions.
Pentoxifylline (PTX) is a promising therapeutic approach for reducing inflammation and improving anemia associated to various systemic disorders. However, whether this agent may be helpful for anemia ...management also in CKD patients is still object of debate.
Systematic review and meta-analysis.
Adults with CKD (any KDOQI stage, including ESKD patients on regular dialysis) and anemia (Hb<13 g/dL in men or < 12 g/dL in women).
Cochrane CENTRAL, EMBASE, Ovid-MEDLINE and PubMed were searched for studies providing data on the effects of PTX on anemia parameters in CKD patients without design or follow-up restriction.
PTX derivatives at any dose regimen.
Hemoglobin, hematocrit, ESAs dosage and resistance (ERI), iron indexes (ferritin, serum iron, TIBC, transferrin and serum hepcidin) and adverse events.
We retrieved 11 studies (377 patients) including seven randomized controlled trials (all comparing PTX to placebo or standard therapy) one retrospective case-control study and three prospective uncontrolled studies. Overall, PTX increased hemoglobin in three uncontrolled studies but such improvement was not confirmed in a meta-analysis of seven studies (299 patients) (MD 0.12 g/dL, 95% CI -0.22 to 0.47). Similarly, there were no conclusive effects of PTX on hematocrit, ESAs dose, ferritin and TSAT in pooled analyses. Data on serum iron, ERI, TIBC and hepcidin were based on single studies. No evidence of increased rate of adverse events was also noticed.
Small sample size and limited number of studies. High heterogeneity among studies with respect to CKD and anemia severity, duration of intervention and responsiveness/current therapy with iron or ESAs.
There is currently no conclusive evidence supporting the utility of pentoxifylline for improving anemia control in CKD patients. Future trials designed on hard, patient-centered outcomes with larger sample size and longer follow-up are advocated.
The EXCITE trial (JASN 28: 1259-1268, 2017) in dialysis patients showed that a 6-month home walking exercise program improves physical function and two dimensions of the KDQOLSF-SF™ questionnaire. ...Whether improvements in physical function achieved by exercise interventions are maintained in the long term has never been tested in the dialysis population.
In this post-trial study embedded in the EXCITE trial we tested the response to the 6MWT and the 5STS tests and the KDQOLSF-SF™ from the 6th month (end of the trial) to the 36th month.
Among the 227 patients of the EXCITE trial cohort, 162 underwent at least three out four testing visits (baseline, 6, 18 and/or 36 month) contemplated by the study protocol and 89 all four testing visits. In the primary analysis by the linear mixed model the gain in walking distance achieved at 6th month in the exercise group (between-arms difference: +36 meters, 95% CI: 22-51, P < 0.001) was maintained at the 18th month (between-arms difference: +37 meters, 95% CI: 19-57, P < 0.001) to reduce to 23 meters (95% CI: -4 to 49 meters, P = 0.10) at 36th month. Overall, the post trial difference in walking distance trajectories between the two study arms was highly significant (P = 0.004). Furthermore, the walking distance changes at the 6th (r = 0.34, P = 0.018) and 18th month (r = 0.30, P = 0.043) were directly related with number of structured exercise sessions completed during the trial (i.e. the first 6 months). No such an effect was registered in the response to the 5STS or in quality of life as measured by the KDQOLSF-SF™.
In dialysis patients the benefits of a 6-months structured walking program outlast the duration of the intervention and postpone the loss of walking performance which naturally occurs in this population but does not affect QoL and the response to the STS test.
Although the number of patients reaching end-stage kidney disease without a biopsy-proven diagnosis is increasing, the utility of renal biopsy is still an object of debate. We analyzed ...epidemiological data and the main indications for renal biopsy with a systematic, evidence-based review at current literature.
There is a high discrepancy observed in biopsy rates and in the epidemiology of glomerular diseases worldwide, related to the different time frame of the analyzed reports, lack of data collection, the different reference source population and the heterogeneity of indications. The evidence-based analysis of indications showed that renal biopsy should be crucial in adults with nephrotic syndrome or urinary abnormalities as coexistent hematuria and proteinuria and in corticosteroid resistant-children with severe proteinuria. The knowledge of renal histology can change the clinical management in patients with acute kidney injury significantly, after the exclusion of pre-renal or obstructive causes of kidney damage. Scarce evidence indicates that renal biopsy can be useful in patients with advanced chronic kidney disease and its use should always be considered after weighing the benefits and potential risks. Renal biopsy should be crucial in patients with renal involvement due to systemic disease. In patients with diabetes with atypical features, renal biopsy may be fundamental to diagnose an unexpected parenchymal disease mislabeled as diabetic nephropathy. Finally, in elderly patients, the indications and the risks are not different from those in the general population.
Renal biopsy still remains a concrete approach for managing a substantial percentage of renal diseases.
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