Influence of prebiotic and probiotic supplementation on the progression of chronic kidney disease. Synbiotic Supplementations for Azotemia in Patients With Chronic Kidney Disease: a Randomized Controlled Trial. Pilot study of probiotic dietary supplementation for promoting healthy kidney function in patients with chronic kidney disease SYNbiotics Easing Renal failure by improving Gut microbiologY (SYNERGY): a protocol of placebo-controlled randomised cross-over trial Effectiveness of multidisciplinary care for chronic kidney disease in Taiwan: a 3-year prospective cohort study. The exclusion of patients with chronic kidney disease from clinical trials in coronary artery disease. Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The Mild to Moderate Kidney Disease (MMKD) Study The Prevalence of Chronic Kidney Disease in a Primary Care Setting: A Swiss Cross-Sectional Study The use of an anti-inflammatory supplement in patients with chronic kidney disease Uric acid and chronic kidney disease: new understanding of an old problem. Effect of probiotics on human blood urea levels in patients with chronic renal failure. Effects of Targeted Interventions on Lifestyle Modifications of Chronic Kidney Disease Patients Association of symptoms of depression with progression of CKD. Probiotic dietary supplementation in patients with stage 3 and 4 chronic kidney disease: a 6-month pilot scale trial in Canada High prevalence of undiagnosed chronic kidney disease among at-risk population in Kinshasa, the Democratic Republic of Congo The kidney and cardiovascular outcome trials. CKD associates with cognitive decline.
BACKGROUND One of the main goals in chronic kidney disease ( CKD ) patients is to diminish the accumulation of uremic toxins and to slow the progression of renal failure . We investigated whether prebiotic and probiotic supplementation along with low protein diet retards the progression of CKD . METHODS This is a 12-month prospect i ve observation study with a r and omized control and open-label design . A total of 24 stable CKD stage III to V patients , who are not on renal replacement therapy , were enrolled in this study . Patients were r and omly assigned to 2 groups : low protein diet + prebiotic + probiotic supplementation ( N.=12 ) , receiving 3 tablets of prebiotic + probiotic supplementation daily for 6 months , and the control group receiving low protein diet only ( N.=12 ) . We examined the effects of prebiotic and probiotic supplementation on estimated glomerular filtration rate ( eGFR ) in CKD . RESULTS The declining GFR  during prebiotic and probiotic supplementation were significantly lower ( -11.6±8.6 vs. -3.4±4.6 mL/min per 1.73 m2 per year , 95 % CI -6.45 - -9.86 , P<0.001 ) than those with low protein diet alone . CONCLUSIONS Prebiotic and probiotic supplementation along with low protein diet delayed the progression of CKD INTRODUCTION Chronic kidney disease ( CKD ) is a progressive and irreversible impairment of kidney function ; if it progresses to the end-stage of CKD , dialysis or kidney transplant is needed . In general , there are no definitive treatment to slow the progression of CKD . This study aim ed to determine the effect of synbiotic supplementations on azotemia in patients with CKD . MATERIAL S AND METHODS A r and omized controlled trial was conducted on 66 patients with CKD ( stages 3 and 4 ) . The participants were r and omly divided into 2 groups to receive synbiotic supplement , 1000 mg/d , and placebo ( 2 capsules a day ) for 6 weeks . At the beginning and end of the study , blood parameters and kidney function were evaluated . RESULTS Of the 66 patients studied , 16 patients ( 24.2 % ) were women and 50 ( 75.8 % ) were men . The mean age and body mass index of the participants were 61 ± 7.65 years and 28.52 ± 4.06 kg/m2 , respectively .  The level of blood urea nitrogen showed a significant reduction following the intake of synbiotic supplement ( from 40.80 ± 22.11 mg/dL to 36.14 ± 20.52 mg/dL , P = .01 ) . Serum creatinine , uric acid , and other indicators of kidney function showed no significant change . CONCLUSIONS The intake of synbiotic supplement could reduce blood urea nitrogen in patients with CKD in stages 3 and 4 ; however , it had no effect on the other markers of kidney function Introduction Uremic syndrome consists of nitrogenous waste retention , deficiency in kidney-derived hormones , and reduced acid excretion , and , if untreated , may progress to coma and eventual death . Previous experience suggests that oral administration of a probiotic formulation of selected microbial strains may extend renoprotection via intraintestinal extraction of toxic waste solutes in patients with chronic kidney disease (CKD)stages 3 and 4 . This report presents preliminary data from a pilot study . Methods This was a 6-month prospect i ve , r and omized , double-blind , placebo-controlled crossover trial of a probiotic bacterial formulation conducted in four countries , at five institutions , on 46 out patients with CKD stages 3 an nd 4 : USA ( n=10 ) , Canada ( n=113 ) , Nigeria ( n=115 ) , and Argentina ( n=8 ) . Outcomes were compared using biochemical parameters : blood urea nitrogen ( BUN ) , serum creatinine , and uric acid . General well-being was assessed as a secondary parameter by a quality of life ( QQOL ) question naire on a subjective scale of 1–10 . Results Oral ingestion of probiotics ( 90 billion colony forming units [CFUs]/day ) was well tolerated and safe during the entire trial period at all sites . BUN levels decreased in 29 patients ( 63 % , P<0.05 ) , creatinine levels decreased in 20 patients ( 43 % , no statistical significance ) , and uric acid levels decreased in 15 patients ( 33 % , no statistical significance ) . Almost all subjects expressed a perceived substantial overall improvement in QOL ( 86 % , P<0.05 ) . Conclusion The main outcomes of this preliminary trial include a significant reduction of BUN , enhanced well-being , and absence of serious adverse effects , thus supporting the use of the chosen probiotic formulation for bowel-based toxic solute extraction . QOL and BUN levels showed statistically significant differences in outcome ( P<0.05 ) between placebo and probiotic treatment periods at all four sites ( 46 patients ) . A major limitation of this trial is the small sample size nd elated inconsistencies Background Emerging evidence suggests modulating the microbiota in the large bowel of patients with chronic kidney disease ( CKD ) through pre- and /probiotic supplementation may inhibit the development of key nephrovascular toxins . To date , quality intervention trials investigating this novel treatment in CKD are lacking . The aim of SYNERGY is to assess the effectiveness of synbiotics ( co-administration of pre- and probiotics ) as a potential treatment targeting the synthesis of uremic toxins , specifically , indoxyl sulphate ( IS ) and p-cresyl sulphate ( PCS ) . Methods / design Thirty-seven patients with moderate to severe CKD ( Stage IV and V , pre-dialysis ) will be recruited to a double-blind , placebo-controlled , r and omised cross-over trial . Patients will be provided with synbiotic therapy or placebo for 6 weeks , with a 4 week washout before cross-over . The primary outcome is serum IS , total and free ( unbound ) concentrations , measured using ultra-performance liquid chromatography . Secondary outcomes include serum PCS , total and free ( unbound ) concentrations ; cardiovascular risk , measured by serum lipopolysaccharides , serum trimethylamine-N-oxide ( TMAO ) and inflammation and oxidative stress markers ; kidney damage , measured by 24 hour proteinuria and albuminuria , estimated glomerular filtration rate and renal tubule damage ( urinary kidney injury molecule-1 ) ; patients ’ self assessed quality of life ; and gastrointestinal symptoms . In addition , the effects on the community structure of the stool microbiota will be explored in a subset of patients to vali date the mechanistic rationale underpinning the synbiotic therapy . Discussion IS and PCS are two novel uremic toxins implicated in both cardiovascular disease ( CVD ) and progression of CKD . Preliminary studies indicate that synbiotic therapy maybe a promising strategy when considering a targeted , tolerable and cost-efficient therapy for lowering serum IS and PCS concentrations . This trial will provide high quality ‘ proof-of-concept ’ data to eluci date both the efficacy of synbiotic therapy for lowering the toxins and whether reductions in serum IS and PCS translate into clinical benefits . Considering the potential of pre- and probiotics to not only shift toxin levels , but to also impede CVD and CKD progression , SYNERGY will provide vital insight into the effectiveness of this innocuous nutritional therapy . Trial Registration Universal Trial Number : U1111 - 1142 - 4363 . Australian New Zeal and Clinical Trials Registry Number : ACTRN12613000493741 , date registered : 2nd May 2013 BACKGROUND Previous studies have demonstrated that multidisciplinary pre-dialysis education and team care may slow the decline in renal function for chronic kidney disease ( CKD ) . Our study compared clinical outcomes of CKD patients between multidisciplinary care ( MDC ) and usual care in Taiwan . METHODS In this 3-year prospect i ve cohort study from 2008 to 2010 , we recruited 1056 CKD subjects , aged 20 - 80 years , from five hospitals , who received either MDC or usual care , had an estimated glomerular filtration rate ( eGFR ) < 60 mL/min , were matched one to one with the propensity score including gender , age , eGFR and co-morbidity diseases . The MDC team was under-cared based on NKF K/DOQI clinical practice guidelines and the Taiwanese pre-end-stage renal disease ( ESRD ) care program . The incidence of progression to ESRD ( initiation of dialysis ) and mortality was compared between two groups . We also monitored blood pressure control , the rate of renal function decline , lipid profile , hematocrit and mineral bone disease control .  RESULTS Participants were prone to be male ( 64.8 % ) with a mean age of 65.1 years and 33.1 months of mean follow-up . The MDC group had higher prescription rates of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker ( ACEI/ARB ) , phosphate binder , vitamin D3 , uric acid lower agents and erythropoietin-stimulating therapy and better control in secondary hyperparathyroidism . The decline of renal function in advanced stage CKD IV and V was also slower in the MDC group ( -5.1 versus -7.3 mL/min , P = 0.01 ) . The use of temporary dialysis catheter was higher in the usual care group , and CKD patients under MDC intervention exhibited a greater willingness to choose peritoneal dialysis modality . A Cox regression revealed that the MDC group was associated with a 40 % reduction in the risk of hospitalization due to infection , and a 51 % reduction in patient mortality , but a 68 % increase in the risk of initiation dialysis when compared with the usual care group . CONCLUSIONS MDC patients were found to have more effective medication prescription according to K/DOQI guidelines and slower renal function declines in advanced/late-stage CKD . After MDC intervention , CKD patients had a better survival rate and were more likely to initiate renal replacement therapy ( RRT ) instead of mortality Chronic kidney disease ( CKD ) is associated with a high risk of death from coronary artery disease and may modify the response to st and ard cardiovascular therapies . Treatment of subjects with CKD should ideally be based on evidence from r and omized , clinical trials , but how often subjects with CKD have been excluded from these trials is uncertain . We undertook this study in order to quantify how often subjects with moderate to advanced CKD were excluded from large cardiovascular trials . MEDLINE and the reference list of selected articles were search ed in order to identify large , r and omized , controlled trials of five different coronary artery disease therapies  published between 1998 and 2005 . Exclusion criteria and reported clinical characteristics of subjects were abstract ed . Rates of exclusion and reporting of baseline characteristics of study participants were compared for CKD , diabetes , history of smoking , and hypertension . Eighty-six trials r and omizing 411 653 patients were identified . More than 80 % of trials excluded subjects with end-stage renal disease and 75.0 % excluded patients with CKD . Subjects with diabetes , hypertension , or a history of smoking  were excluded less than 4 % of the time . Baseline renal function of study participant was reported in only 7 % of trials . Patients with CKD are frequently excluded from coronary artery disease trials and renal function of r and omized subjects is rarely reported . These findings reinforce the notion that available data on the treatment of coronary artery disease in subjects with CKD have significant limitations and should be generalized to the treatment of subjects with CKD cautiously The kidney is one of the organs most prominently affected by aging . This can be seen by a loss of renal mass which is caused by a decrease in the number of nephrons result ing in hyperfiltration , hypertrophy and elevations in glomerular pressure . The factors influencing aging of the kidney are not fully eluci date d. Epidemiological , experimental and interventional studies result ed in inconsistent results and have not firmly established whether uric acid levels affect progression of Chronic Kidney Disease ( CKD ) . Therefore , we analyzed whether uric acid levels predict the progression of CKD in the Mild to Moderate Kidney Disease Study comprising at baseline 227 Caucasian patients aged 18 - 65 years with primary non-diabetic CKD of various degrees of renal impairment . Of them , 177 completed a prospect i ve follow-up of 7 years . Primary endpoint was progression of CKD defined as doubling of baseline serum creatinine and /or terminal renal failure . Patients who reached a progression endpoint ( n = 6 5 ) were significantly older , had higher baseline serum creatinine and protein excretion rates as well as lower Glomerular Filtration Rate ( GFR ) . Uric acid levels were only higher in patients with progression of disease when patients with uric acid-lowering drugs were excluded from the analysis . Cox regression analysis revealed that increasing uric acid levels predict disease progression only when the analysis was not adjusted for baseline kidney function parameters . As soon as we adjusted the analysis for GFR and proteinuria this association completely vanished . In summary , our prospect i ve 7 year follow-up study in patients with non-diabetic primary CKD did not support uric acid as an independent predictor for CKD progression Chronic kidney disease ( CKD ) often remains clinical ly silent and therefore undiagnosed until a progressed stage is reached . Our aim was to estimate the prevalence of CKD in a primary care setting in Switzerl and . A multicenter , cross-sectional study with r and omly selected general practitioners was performed . Adults visiting their general physician ’s cabinet during defined periods were asked to participate  . Baseline information was reported on a question naire , urine and blood sample s were analyzed in a central laboratory . Renal status was assessed using the Kidney Disease : Improving Global Outcomes ( KDIGO ) classification . Extrapolation of results to national level was adjusted for age and gender . One thous and individuals ( 57 % females ) with a mean age of 57±17 years were included . Overall , 41 % of the patients had normal estimated glomerular filtration rate ( eGFR ) and albumin creatinine ratio ( ACR ) , whereas 36 % of the subjects had slightly reduced excretory renal function with physiological albuminuria based on normal ACR . Almost one fourth of the subjects ( 23 % ) had either a substantially reduced eGFR or high levels of ACR . About 10 % of the patients had a substantially reduced eGFR of < 60 ml/min/1.73 m2 , and 17 % showed relevant proteinuria ( ACR > 30 mg/g creatinine ) . Extrapolation to national level suggests that about 18 % of primary care patients may suffer from CKD . CKD prevalence in a primary care population is therefore high , and preventive interventions may be advisable , in particular as CKD prevalence is likely to rise over the next decades Abstract Chronic kidney disease ( CKD ) is characterized by a continuous reduction in kidney function , increased inflammation , and reduced antioxidant capacity . The objective of this study was to assess the effects of a herbal supplement on systemic inflammation and antioxidant status in non-dialysis CKD patients . Sixteen patients with CKD ( 56.0±16.0 yrs , 171.4±11.9 cm , 99.3±20.2 kg ) were r and omly chosen to receive a herbal supplement composed of Curcuma longa and Boswellia serrata , or placebo . Plasma levels of interleukin-6 ( IL-6 ) , tumor necrosis factor-α ( TNF-α ) , glutathione peroxidase ( GPx ) , and serum C-reactive protein ( CRP ) were measured at baseline and 8 weeks . Baseline data demonstrated elevated inflammation and low antioxidant levels . A significant time effect ( p=0.03 ) and time x compliance interaction effect ( p=0.04 ) were observed for IL-6 . No significant differences were observed for any other variables . This study demonstrates that mild and moderate CKD is associated with chronic inflammation and low antioxidant activity . Systemic inflammation and impaired antioxidant status may be greater in CKD population s with multiple comorbidities . Curcumin and Boswellia serrata are safe and tolerable and helped to improve the levels of an inflammatory cytokine Although an elevation of serum uric acid level is often associated with chronic kidney disease ( CKD ) , it remains controversial whether hyperuricemia per se is a true risk factor for the development or aggravation of CKD . Recent epidemiologic studies in healthy population s or in subjects with established kidney disease have reported the independent role of uric acid in lowering glomerular filtration rate and increasing the risk for new-onset kidney disease . Furthermore , lowering uric acid in patients with established renal disease has been reported to stabilize renal function independent of other confounders , suggesting a causative role of elevated uric acid in progression of CKD , rather than as an incidental finding related to CKD severity . In this manuscript we will discuss the potential role of uric acid in the development and aggravation of CKD based on epidemiologic , clinical and experimental studies . Given the worldwide epidemic of CKD , the importance of identifying modifiable risk factors of CKD , and the clinical implication of hyperuricemia in CKD , we propose large r and omized clinical trials to investigate whether uric acid-lowering therapy can slow the progression of CKD INTRODUCTION Patients with chronic kidney disease ( CKD ) show an increase in bowel aerobic bacteria that produce uremic toxins and decreased anaerobic bacteria as bifidobacteria and lactobacillus . The latter can be used as probiotics . The probiotic with greater availability in Mexico , is the lactobacillus casei shirota ( LcS ) , currently there is no known LcS specified dose that produces a benefit to the patient with CKD . OBJECTIVE To determine the effectiveness of two different LcS doses in achieving a decrease in urea concentrations of at least 10 % in patients with KDOQI stage 3 and stage 4 CKD . METODOLOGY : A simple r and omized , controlled clinical trial . Out patients treated at the National Institute of Medical Sciences and Nutrition Salvador Zubirán in México D.F. Patients were provided the LcS , as follows : Group A : 8 x 10(9 ) colony-forming units ( CFU ) and Group B : 16 x 10(9 ) CFU . Patients were followed-up for eight weeks , and baseline and final sample s were obtained to calculate the basal and final concentrations , respectively , of blood urea and serum creatinine ( CrS ) . During the follow-up , both groups consumed a diet of 30 kcal/kg/weight and 0.8 g/kg/weight of protein , and a food diary was made to assess both the adherence to the diet  and  LcS.  RESULTS Thirty patients with CKD were evaluated . When analyzing the percentage change between the different doses , a decrease > 10 % was found in the blood urea concentrations for patients treated with the 16 x 109 dose , which was significant with respect to the baseline measurement . CONCLUSION There was a > 10 % decrease in the serum urea concentrations with LcS in patients with stage 3 and 4 CRF Targeting interventions to an individual ’s readiness to modify lifestyle factors , specifically diet and exercise behaviors , may delay chronic kidney disease ( CKD ) progression . This study examined the effects of a targeted Lifestyle Modification Program based on the readiness to change health-promotion lifestyle behaviors , renal protection knowledge , and physical indicators of patients with early CKD . A repeated- measures design r and omized 160 CKD patients from four southern Taiwan outpatient nephrology clinics into control and intervention groups  . Data were collected five times over a year with a participant retention rate of 64.4 % . The intervention group demonstrated significant improvement with regard to diet behavior modifications . Compared with the control group , the intervention group showed a significant improving trend of renal function protection knowledge , stress management , and interpersonal relations . Targeted interventions for patients in the early phases of CKD promotes adherence to proper diet , exercise behavior , and positive lifestyle modifications BACKGROUND Depression is related to morbidity and mortality in patients with kidney failure treated by dialysis , but its influence on patients with earlier stages of chronic kidney disease ( CKD ) is uncertain . This study investigates the association of depressive symptoms with clinical outcomes in patients with CKD not requiring dialysis . STUDY DESIGN Prospect i ve observational cohort study . SETTING & PARTICIPANTS 568 participants with CKD not requiring maintenance dialysis were recruited consecutively at a tertiary hospital in Southern Taiwan and followed up for 4 years . PREDICTORS Baseline status of depressive symptoms . OUTCOMES The primary outcome is a composite of progression to end-stage renal disease ( ESRD ) , defined as requiring maintenance dialysis treatment  , or all-cause mortality ; and secondary outcome was first hospitalization . MEASUREMENTS Depressive symptoms were assessed by  Beck Depression Inventory .  Estimated glomerular filtration rate ( eGFR ) was computed using the 4-variable MDRD ( Modification of Diet in Renal Disease ) Study equation . RESULTS 428 participants completed the question naires and 160 ( 37 % ) had depressive symptoms . During a mean follow-up of 25.2 ± 11.9 months , 136 participants ( 32 % ) reached the primary outcome ( 119 reached ESRD and 17 died ) and 110 participants ( 26 % ) were hospitalized . High depressive symptoms increased the risk of progression to ESRD or death ( HR , 1.66 ; 95 % CI , 1.14 - 2.44 ) and first hospitalization ( HR , 1.59 ; 95 % CI , 1.03 - 2.47 ) . Participants with high depressive symptoms had more rapid GFR decrease ( eGFR slopes of -2.3 [ 25th-75th percentile , -5.3 to -0.4 ] vs -1.2 [ 25th-75th percentile , -3.5 to 0.3 ] mL/min/1.73 m(2 ) per year ; P = 0.001 ) and initial dialysis treatment at a higher eGFR ( OR for initiation of dialysis at eGFR > 5 mL/min/1.73 m(2 ) , 4.45 ; 95 % CI , 1.44 - 13.78 ) . LIMITATIONS A single-center study of Taiwanese , Beck Depression Inventory evaluates only depressive symptom burden . CONCLUSIONS Depressive symptoms in CKD are independent predictors of adverse clinical outcomes , including faster eGFR decrease , dialysis therapy initiation , death , or hospitalization . Depression should be evaluated early and treated in patients with CKD ABSTRACT Aim : This was a pilot clinical trial to assess biochemical and clinical effects of an oral probiotic dietary supplement in chronic kidney disease ( CKD ) patients ( stages 3 and 4 ) . Methods : A prospect i ve , r and omized , double-blind , crossover , placebo-controlled , 6-month trial of probiotic bacteria was conducted in 16 out patients in Ontario , Canada . Primary endpoints included effect on hematologic , biochemical , and fecal variables , and on general well-being as assessed by quality of life ( QOL ) . These outcomes were evaluated from biochemical parameters , mainly blood urea nitrogen ( BUN ) , creatinine , uric acid , and C-reactive protein ( CRP ) as a general inflammatory marker . QOL was assessed on a subjective scale of 1 to 10 as the secondary parameter . Trial registration : This pilot study forms part of registered trial NCT00760162 . Results : A total of 13 patients completed the study . Three patients dropped out : one was the receiver of a transplant . The second dropped out for unknown reasons and the third died of myocardial infa rct ion ( unrelated to probiotic bacteria or the protocol ) . Among the 13 patients who completed the trial , the mean change in BUN concentration during the probiotic treatment period ( −2.93 mmol/L ) differed significantly ( p = 0.002 ) from the mean change in BUN concentration during the placebo period ( 4.52 mmol/L ) . In addition , the mean changes in uric acid concentration were moderate during the KB period ( 24.70 μmol/L ) versus during the placebo period ( 50.62 μmol/L , p = 0.050 ) , and the changes in serum creatinine concentration were insignificant . Neither gastrointestinal nor infectious complications were noted in any subject with improved QOL . Conclusion : Orally administered probiotic bacteria selected to metabolize nitrogenous wastes may be tolerated for as long as 6 months . A major limitation of this trial is its small size that may have precluded detection of changes in other biochemical or hematologic parameters that would be evident in larger cohorts . Extension of the evaluation of this probiotic bacterial mixture will include a dose escalation trial in a similar prospect i ve , placebo-controlled , and double-blind study site Background There is limited knowledge of Chronic Kidney Disease ( CKD ) among high risk population s , especially in the developing countries . We report our study of testing for CKD in at-risk subjects . Methods In a cross-sectional study , 527 people from primary and secondary health care areas in the city of Kinshasa were studied from a r and om sample of at-risk out- patients with hypertension , diabetes , obesity , or HIV+ . We  measured blood pressure ( BP ) , blood glucose level , proteinuria , body mass index , and estimated glomerular filtration rate ( eGFR by MDRD equation ) using calibrated creatinine levels based on one r and om measurement . The associations between health characteristics , indicators of kidney damage ( proteinuria ) and kidney function ( < 60 ml/min/1.73 m2 ) were also examined . Results The prevalence of CKD in this study was 36 % , but only 12 % were aware of their condition . 4 % of patients had stage 1 CKD , 6 % stage 2 , 18 % stage 3 , 2 % stage 4 , and 6 % had stage 5 . 24 hour quantitative proteinuria ( > 300 mg/day ) was found in 19 % . In those with the at-risk conditions , the % of CKD was : 44 % in patients with hypertension , 39 % in those with diabetes ; 16 % in the obese and 12 % in those who were HIV+ . 82 % of those with a history of diabetes had elevated serum glucose levels at screening ( ≥ 126 mg/dl ) . Only 6 % of individuals with hypertension having CKD had reduced BP to lower than 130/80 mmHg . In multivariate analysis , diabetes , proteinuria and hypertension were the strongest determinants of CKD 3 + . Conclusion It appears that one out of three people in this at-risk population has undiagnosed CKD and poorly controlled CKD risk factors . This growing problem poses clear challenges to this developing country . Therefore , CKD should be addressed through the development of multidisciplinary teams and improved communication between traditional health care givers and nephrology services . Attention to CKD risk factors must become a priority Chronic kidney disease ( CKD ) affects a substantial minority of people with type 2 diabetes ( T2D ) . Analysis of US National Health and Nutrition Examination Survey ( NHANES ) data sets from 2007 through 2012 showed Stage 3 or worse disease ( estimated glomerular filtration rate [ eGFR ] < 60 mL/min per 1.73 m2 ) in nearly one in five patients , with increasing age , blood pressure , obesity , and levels of glycemia all associated with higher likelihood of Stage 3 or worse CKD , comparable to findings from surveys from many other areas , which also show micro- or macroalbuminuria to be present in one-sixth to one-third of diabetic people . Improvement in albuminuria has been shown in clinical trials of glycemic interventions , including the Action to Control Cardiovascular Disease in Diabetes ( ACCORD ) trial , the Action in Diabetes and Vascular Disease : Preterax and Diamicron MR Controlled Evaluation ( ADVANCE ) trial , in which the nephroprotective effect of blood pressure lowering was also demonstrated , and the UK Prospect i ve Diabetes Study ( UKPDS ) . However , over the past decade a host of cardiovascular outcome trials ( CVOTs ) have been performed with newer T2D therapeutic agents , and many of these have included intriguing information pertaining to renal disease and renal outcomes not necessarily related to changes in glycemia . It is of interest to review some of these findings . Glucagon-like peptide-1 ( GLP-1 ) has been reported to increase glomerular filtration rate ( GFR ) , renal blood flow , and the fractional excretion both of sodium and potassium , with renal GLP-1 receptors present in afferent arteriolar vascular smooth muscle cells , glomerular endothelial cells and macrophages , juxtaglomerular cells , and the proximal tubule , perhaps mediating the greater natriuresis seen after oral than intravenous sodium . In the Liraglutide Effect and Action in Diabetes : Evaluation of Cardiovascular Outcome Results ( LEADER ) trial , the significant 13 % reduction in the primary composite outcome of cardiovascular death , myocardial infa rct ion , and stroke was found on subgroup analysis to particularly occur among participants with Stage 3 CKD , having eGFR 30 - 59 mL/min per 1.73 m2 . No significant effect on eGFR was found with liraglutide , although both those receiving and not receiving the drug showed a decline in eGFR from approximately 75 to 65 mL/min per 1.73 m2 over the 48-month period of observation . Liraglutide administration was associated with a significant reduction in albuminuria , with nearly a 25 % lower likelihood of development of macroalbuminuria , and with the albumin : creatinine ratio ( ACR ) approximately 20 % lower among treated people , regardless of the baseline level of eGFR . Similarly , in the Evaluation of Lixisenatide in Acute Coronary Syndrome ( ELIXA ) trial , a 34 % increase in the urine ACR was reported among people receiving placebo , but the increase was 24 % among those receiving lixisenatide , and in the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes ( SUSTAIN-6 ) , persistent macroalbuminuria developed among 2.7 % of those receiving semaglutide , but among 4.9 % of those receiving placebo . The enzyme dipeptidyl peptidase (DPP)-4 is , like the GLP-1 receptor , present in multiple renal membrane-bound locations , including afferent arteriolar vascular smooth muscle cells , mesangial cells , podocytes , and proximal tubular cells , and DPP-4 inhibitors appear to have salutary effects on albuminuria similar to those of the GLP-1 agents . In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-Thrombolysis in Myocardial Infa rct ion ( TIMI ) 53 trial , saxagliptin was associated with significantly less worsening and more improvement in microalbumin levels at 1 year , at 2 years , and by end-of-treatment . The reduction in microalbumin levels was similar in patients with and without renal impairment . Interestingly , there was no relationship between improvement in albuminuria and improvement in HbA1c . The other DPP4i CVOTs have not reported effects of these agents on renal function or albuminuria , but studies of sitagliptin and linagliptin suggest that these agents may also reduce albuminuria . Sodium-glucose cotransporter ( SGLT ) 2 inhibitors affect multiple sites , with the potential to affect renal function . The Canagliflozin Cardiovascular Assessment Study ( CANVAS ) showed a 27 % reduction in progression of albuminuria , with a 40 % reduction in eGFR , need for renal-replacement therapy , or death from renal causes associated with the use of canagliflozin . After a fall in mean eGFR with canagliflozin from 76 to 73 mL/min per 1.73 m2 at 3 months , eGFR remained stable through 6 years while gradually declining during the period of observation with placebo . Evidence of dual effects of SGLT2 inhibition on both albuminuria and GFR was even more strongly shown in the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients ( EMPA-REG OUTCOME ) ; in that CVOT , although there was an initial decline in eGFR with empagliflozin , from 94 mL/min per 1.73 m2 through 192 weeks , eGFR was consistently higher with empagliflozin , although this was less clear in trial participants with baseline eGFR < 60 mL/min per 1.73 m2 . Empagliflozin also reduced the development of acute renal failure . Further analysis showed empagliflozin to be associated with a reduction in albuminuria , regardless of the baseline urine albumin level . The CVOTs have offered the possibility that diabetes treatment may move beyond surrogate endpoints to actual cardiovascular outcome benefits . It appears that these drugs will also lead to a reduction in adverse renal outcomes . We should look with optimism at this potential approach to a major complication of diabetes Cognitive impairment and chronic kidney disease ( CKD ) will become increasingly prevalent in the aging US population . Although evidence exists that CKD is a risk factor for cognitive decline , longitudinal studies are limited and largely have excluded ethnically diverse population s. The Northern Manhattan Study includes a population -based , prospect i ve , stroke-free cohort . We assessed global cognitive function annually using the  modified Telephone Interview for Cognitive Status ( TICS-m )  and estimated kidney function using Cockcroft-Gault creatinine clearance ( CCl ) , Modification of Diet in Renal Disease estimated GFR ( eGFR ) , and serum creatinine ( sCr ) .  We examined the association between CKD and change in TICS-m scores over time , adjusting for sociodemographic and vascular risk factors . Of 2172 subjects ( mean age 71.5 yr , mean follow-up 2.9 yr ) , 59 % were Hispanic , 20 % were black , and 63 % were women . Participants with a CCl < 60 ml/min and those with a CCl between 60 and 90 ml/min performed significantly worse on the TICS-m over time than those with a CCl > 90 ml/min , adjusting for potential confounders . Our results were similar when we used eGFR or sCr to estimate kidney function . In conclusion , decreased kidney function associates with greater cognitive decline , even in those with mild CKD . Kidney disease may represent a novel mechanism leading to cognitive impairment and a target for early intervention
Most of the included articles reported positive effects in renal function and decreased levels of urea , blood urea nitrogen , ammonia , plasma p-cresol , p-cresyl sulfate , and indoxyl sulfate
ABSTRACT Chronic kidney disease ( CKD ) is a syndrome caused by the progressive reduction of renal function .
This study aim ed to systematic ally examine the effects of supplementation with probiotics in the treatment of CKD .