Cystatin C Is a Gender-Neutral Glomerular Filtration Rate Biomarker in Patients with Cirrhosis

Background

Lower serum Cr levels in women as compared to men result in underestimation of renal dysfunction and lower model for end-stage liver disease-sodium scores leading to reduced access to liver transplantation in women compared to men with comparable hepatic dysfunction.

Aim

The aim of this study was to determine the gender differences in serum Cr, cystatin C, and other endogenous glomerular filtration rate (GFR) biomarkers, measured and estimated GFR, Cr clearance, and Cr production rates.

Methods

We measured GFR by iothalamate plasma clearance in 103 patients with cirrhosis and assessed gender differences in GFR, Cr clearance and production rate, serum Cr, cystatin C and other endogenous GFR biomarkers including beta-trace protein, beta-2 microglobulin, and dimethylarginines.

Results

Comparison of men and women showed significantly lower values for mean serum Cr (0.97 vs. 0.82 mg/dl, P = 0.023), and Cr production rate (13.37 vs. 11.02 mg/kg/day, P = 0.022). In contrast to the serum Cr and Cr production rate, men and women exhibited no significant differences in the means of serum cystatin C and other GFR biomarkers, measured GFR, GFR estimated using Cr–cystatin C GFR equation for cirrhosis, measured and estimated Cr clearances. After controlling for age, race, weight, height, and GFR, female gender remained associated with lower serum Cr levels (P = 0.003). Serum cystatin C levels were not associated with gender, age, race, weight, height, C-reactive protein, and history of hypothyroidism.

Conclusions

Our results suggest that cystatin C and endogenous GFR biomarkers other than Cr, measured GFR, GFR estimated by Cr–cystatin C GFR equation for cirrhosis, measured and estimated Cr clearance minimized between-gender biases in accounting for renal function in patients with cirrhosis. Therefore, serum cystatin C should be measured as a complementary test to serum Cr when renal function is assessed in patients with cirrhosis, particularly in women and those with sarcopenia.

     

Chronic kidney disease and underdiagnosis of renal insufficiency among diabetic patients attending a hospital in Southern Ethiopia

Background

Diabetic patients with chronic kidney disease (CKD), as defined by a reduced glomerular filtration rate (GFR), are at greater risk for cardiovascular and renal events and mortality. The aim of this study was to determine the prevalence of CKD among diabetic patients attending a hospital in southern Ethiopia, and to assess underdiagnosis of renal insufficiency among those with normal serum creatinine.

Methods

A total of 214 randomly selected diabetics attending the follow-up clinic at Butajira hospital of southern Ethiopia participated in this study during the period from September 1 to October 31, 2013. All patients completed an interviewer-administered questionnaire and underwent clinical assessment. The simplified Modification of Diet in Renal Disease (MDRD) and Cockroft-Gault (C-G) equations were used to estimate GFR (eGFR) from serum creatinine.

Results

CKD, defined as eGFR?<?60 ml/min/1.73 m², was present in 18.2% and 23.8% of the study participants according to the MDRD and Cockcroft-Gault (C-G) equations, respectively. Only 9.8% of the total participants, and 48.7% (for the MDRD) and 37.3% (for C-G) of those with eGFR <60 ml/min/1.73 m² had abnormal serum creatinine values, i.e. > 1.5 mg/dl. Normal serum creatinine was observed in 90.2% of participants attending the hospital. A large proportion of participants ranging from 38.9-56.5% have shown to have mild to moderate renal insufficiency (stage 2–3 CKD) despite normal creatinine levels. CKD, eGFR?<?60 ml/min/1.73 m², was found in 10.4 and 16.9% of participants with normal serum creatinine using the MDRD and C-G equations, respectively.

Conclusion

CKD is present in no less than 18% of diabetics attending the hospital, but it is usually undiagnosed. A significant number of diabetics have renal insufficiency corresponding to stages 2–3 CKD despite normal creatinine levels. Therefore, GFR should be considered as an estimate of renal insufficiency, regardless of serum creatinine levels being in normal range.

     

The use of absolute values improves performance of estimation formulae: a retrospective cross sectional study

Background

Estimation of Glomerular Filtration Rate (GFR) by equations such as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or Modification of Diet in Renal Disease (MDRD) is usually expressed as a Body Surface Area (BSA) indexed value (ml/min per 1.73 m²). This can have severe clinical consequences in patients with extreme body sizes, resulting in an underestimation in the case of obesity or an overestimation of GFR in the case of underweight patients. The aim of this study was to compare the performance of both estimation formula expressed in ml/min, instead of ml/min per 1.73 m², with a reference method.

Methods

Retrospective single centre cross sectional study of 185 patients. GFR was measured with ⁵¹Cr-EDTA and estimated with CKD-EPI and MDRD. Bias, precision and accuracy of absolute estimated GFR was calculated.

Results

Bias of CKD-EPI and MDRD formulae expressed as an absolute value was 0.49 and 0.27 ml/min respectively, which is lower than previously reported. Precision was 12.95 and 16.33 and accuracy expressed as P30 was over 92.43% for CKD-EPI. There were no significant differences in GFR between the reference method and the estimation formulae.

Conclusions

The performance of CKD-EPI and MDRD formulae can be significantly improved in the individual patient if the absolute values are used by removing the BSA normalization factor. Absolute estimated GFR by CKD-EPI is comparable to measured GFR, improving the performance of this formula in the assessment of individual kidney function, thus providing clinicians with an alternative to reference methods.

     

Association of Frailty based on self-reported physical function with directly measured kidney function and mortality

Background

Use of serum creatinine to estimate GFR may lead to underestimation of the association between self-reported frailty and kidney function. Our objectives were to evaluate the association of measured GFR (mGFR) with self-reported frailty among patients with CKD and to determine whether self-reported frailty was associated with death after adjusting for mGFR.

Methods

Participants in the Modification of Diet in Renal Disease study (1989–1993) had GFR measured using iothalamate clearance (mGFR), and GFR was estimated based on the CKD-EPI creatinine (eGFRcr) and cystatin C (eGFRcys) equations. We defined self-reported frailty as three or more of: exhaustion, poor physical function, low physical activity, and low body weight. Death was ascertained through 2007 using the National Death Index and the United States Renal Data System.

Results

Eight hundred twelve MDRD participants (97 %) had complete data on self-reported frailty (16 % prevalence, N?=?130) and mGFR (mean (SD) 33.1?±?11.7 ml/min/1.73 m²). Higher GFR was associated with lower odds of self-reported frailty based on mGFR, (OR 0.71, 95 % CI 0.60–0.86 per 10 ml/min/1.73 m²), eGFRcr (OR 0.80, 95 % CI 0.67–0.94 per 10 ml/min/1.73 m²), and eGFRcys (OR 0.75, 95 % CI 0.62–0.90 per 10 ml/min/1.73 m²). Median follow-up was 17 (IQR 11–18) years, with 371 deaths. Self-reported frailty was associated with a higher risk of death (HR 1.71, 95 % CI 1.26–2.30), which was attenuated to a similar degree when mGFR (HR 1.48, 95 % CI 1.08–2.00), eGFRcr (HR 1.57, 95 % CI 1.15–2.10), or eGFRcys (HR 1.51, 95 % CI 1.10–2.10) was included as an indicator of kidney function.

Conclusions

We found an inverse association between kidney function and self-reported frailty that was similar for mGFR, eGFR and eGFRcys. In this relatively healthy cohort of clinical trial participants with CKD, using serum creatinine to estimate GFR did not substantially alter the association of GFR with self-reported frailty or of self-reported frailty with death.

     

Serum cystatin C is a determinant of central pressure augmentation index measured by oscillometric method in renal transplant recipients

Background

Serum cystatin C (ScysC) may help predicting cardiovascular outcome not only through its ability to detect renal dysfunction but also through its potential connection to others factors that are directly related to cardiovascular diseases. We explored the potential association of ScysC with arterial stiffness - a major contributor to cardiovascular disease - in renal transplant recipients (RTR).

Methods

Traditional and non-traditional cardio-vascular risk factors were collected from 215 stable RTR whom arterial stiffness was evaluated by the measure of the augmentation index of central pressure (AIx) determined by the arteriograph device. Serum creatinine and ScysC were measured the same day using standardized methods. Association between ScysC and AIx was examined in univariate and multivariate linear regression analysis.

Results

In univariate analysis, ScysC was strongly associated with AIx. This relationship was not confounded by age, gender, length of time spent on dialysis and transplantation vintage. Adjustment on the level of GFR estimated by the MDRD Study equation attenuated but did not abolish the association between ScysC and AIx.

Conclusions

In conclusion, ScysC is an independent predictor of AIx in RTR. Our data suggest that arterial stiffness may partially mediate the association between ScysC and cardiovascular risk in renal transplantation.

     

Treatment with Dalteparin is Associated with a Lower Risk of Bleeding Compared to Treatment with Unfractionated Heparin in Patients with Renal Insufficiency

BACKGROUND

Low molecular weight heparins (LMWHs) have been cautiously used in patients with chronic kidney disease (CKD) due to fear of accumulation. Dalteparin, however, has shown minimal tendency to accumulate in patients with CKD and may be safe to use in this patient population.

OBJECTIVE

We compared the incidence of clinically significant bleeding in patients with CKD receiving therapeutic doses of dalteparin to that of patients with CKD receiving therapeutic doses of UFH.

DESIGN

This was a retrospective cohort study.

SUBJECTS

Inpatients with CKD (GFR?<?60 ml/min) who were treated with therapeutic dalteparin or UFH were included in the study

MAIN MEASURES

Primary outcome was major bleeding within 10 days of anticoagulation, identified by ICD-9 code and confirmed by chart review. Demographic characteristics, laboratory values, comorbidities, prior bleeding history and inpatient medications were extracted for each admission from the electronic medical record. Logistic regression models were created to examine the association between choice of anticoagulant and bleeding rates, after adjustment for demographic and clinical characteristics.

KEY RESULTS

Dalteparin-treated patients were significantly less likely to experience a major bleed than patients treated with UFH (1.14 % vs. 3.49 %, p?<?0.001). The reduced likelihood of bleeding associated with dalteparin treatment remained significant after adjustment for patient characteristics (HR 0.39, 95 % CI: 0.21–0.70, p?<?0.0001). A stratified analysis for subgroups with GFR< 30 mL/min and with GFR between 30 and 60 mL/min showed that dalteparin was still associated with lower odds of bleeding compared to treatment with unfractionated heparin, but the difference was nonsignificant for GFR< 30 (HR 0.35, 95 % CI: 0.11–1.15), even after adjustment (OR 0.37, 95 % CI: 0.11–1.22).

CONCLUSION

In patients with CKD, treatment with therapeutic dose dalteparin was associated with lower rates of bleeding than treatment with unfractionated heparin. For patients with severe CKD (GFR< 30), dalteparin was shown to be at least as safe as unfractionated heparin.

     

Urinary mitochondrial DNA level as a biomarker of tissue injury in non-diabetic chronic kidney diseases

Background

Urinary mitochondrial DNA (mtDNA) fragment level has been proposed as a biomarker of chronic kidney disease (CKD). In this study, we determine the relation between urinary mtDNA level and rate of renal function deterioration in non-diabetic CKD.

Methods

We recruited 102 non-diabetic CKD patients (43 with kidney biopsy that showed non-specific nephrosclerosis). Urinary mtDNA level was measured and compared to baseline clinical and pathological parameters. The patients were followed 48.3?±?31.8?months for renal events (need of dialysis or over 30% reduction in estimated glomerular filtration rate [eGFR]).

Results

The median urinary mtDNA level was 1519.42 (inter-quartile range 511.81–3073.03) million copy/mmol creatinine. There were significant correlations between urinary mtDNA level and baseline eGFR (r?=?0.429, p?<?0.001), proteinuria (r?=?0.368, p?<?0.001), severity of glomerulosclerosis (r?=???0.537, p?<?0.001), and tubulointerstitial fibrosis (r?=???0.374, p?=?0.014). The overall rate of eGFR decline was ??2.18?±?5.94?ml/min/1.73m² per year. There was no significant correlation between the rate of eGFR decline and urinary mtDNA level. By univariate analysis, urinary mtDNA level predicts dialysis-free survival, but the result became insignificant after adjusting for clinical and histological confounding factors.

Conclusion

Urinary mtDNA levels have no significant association with the rate of renal function decline in non-diabetic CKD, although the levels correlate with baseline renal function, proteinuria, and the severity of histological damage. Urinary mtDNA level may be a surrogate marker of permanent renal damage in non-diabetic CKD.

     

Physical activity and metabolic health in chronic kidney disease: a cross-sectional study

Background

Patients with chronic kidney disease (CKD) are at high risk of progression to end stage renal disease and cardiovascular events. Physical activity may reduce these risks by improving metabolic health. We tested associations of physical activity with central components of metabolic health among people with moderate-severe non-diabetic CKD.

Methods

We performed a cross-sectional study of 47 people with CKD (estimated GFR <60 ml/min/1.73 m²) and 29 healthy control subjects. Accelerometry was used to measured physical activity over 7 days, the hyperinsulinemic-euglycemic clamp was used to measure insulin sensitivity, and DXA was used to measured fat mass. We tested associations of physical activity with insulin sensitivity, fat mass, blood pressure, serum lipid concentrations, and serum high sensitivity C-reactive protein concentration using multivariable linear regression, adjusting for possible confounding factors.

Results

Participants with CKD were less active than participants without CKD (mean (SD) 468.1 (233.1) versus 662.3 (292.5) counts per minute) and had lower insulin sensitivity (4.1 (2.1) versus 5.2 (2.0 (mg/min)/(μU/mL)), higher fat mass (32.0 (11.4) versus 29.4 (14.8) kg), and higher triglyceride concentrations (153.2 (91.6) versus 99.6 (66.8) mg/dL). With adjustment for demographics, comorbidity, medications, and estimated GFR, each two-fold higher level of physical activity was associated with a 0.9 (mg/min)/(μU/mL) higher insulin sensitivity (95% CI 0.2, 1.5, p?=?0.006), an 8.0 kg lower fat mass (?12.9, ?3.1, p?=?0.001), and a 37.9 mg/dL lower triglyceride concentration (?71.9, ?3.9, p?=?0.03). Associations of physical activity with insulin sensitivity and triglycerides did not differ significantly by CKD status (p-values for interaction >0.3).

Conclusions

Greater physical activity is associated with multiple manifestations of metabolic health among people with moderate-severe CKD.

     

Aspirin for Primary Prevention of Cardiovascular Disease and Renal Disease Progression in Chronic Kidney Disease Patients: a Multicenter Randomized Clinical Trial (AASER Study)

Background

Patients with chronic kidney disease (CKD) are at high risk for developing cardiovascular events. However, limited evidence is available regarding the use of aspirin in CKD patients to decrease cardiovascular risk and to slow renal disease progression.

Study Design

Prospective, multicenter, open-label randomized controlled trial.

Setting and Participants

One hundred eleven patients with estimated glomerular filtration rate (eGFR) 15–60 ml/min/1.73 m² without previous cardiovascular events.

Intervention

Aspirin treatment (100 mg/day) (n?=?50) or usual therapy (n?=?61). Mean follow-up time was 64.8?±?16.4 months.

Outcomes

The primary endpoint was composed of cardiovascular death, acute coronary syndrome (nonfatal MI, coronary revascularization, or unstable angina pectoris), cerebrovascular disease, heart failure, or nonfatal peripheral arterial disease. Secondary endpoints were fatal and nonfatal coronary events, renal events (defined as doubling of serum creatinine, ≥?50% decrease in eGFR, or renal replacement therapy), and bleeding episodes.

Results

During follow-up, 17 and 5 participants suffered from a primary endpoint in the control and aspirin groups, respectively. Aspirin did not significantly reduce primary composite endpoint (HR, 0.396 (0.146–1.076), p?=?0.069. Eight patients suffered from a fatal or nonfatal coronary event in the control group compared to no patients in the aspirin group. Aspirin significantly reduced the risk of coronary events (log-rank, 5.997; p?=?0.014). Seventeen patients in the control group reached the renal outcome in comparison with 3 patients in the aspirin group. Aspirin treatment decreased renal disease progression in a model adjusted for age, baseline kidney function, and diabetes mellitus (HR, 0.272; 95% CI, 0.077–0.955; p?=?0.043) but did not when adjusted for albuminuria. No differences were found in minor bleeding episodes between groups and no major bleeding was registered.

Limitations

Small sample size and open-label trial.

Conclusions

Long-term treatment with low-dose aspirin did not reduce the composite primary endpoint; however, there were reductions in secondary endpoints with fewer coronary events and renal outcomes. ClinicalTrials.gov Identifier: NCT01709994.

     

Mortality Associated with Metformin Versus Sulfonylurea Initiation: A Cohort Study of Veterans with Diabetes and Chronic Kidney Disease

Background

For patients with type 2 diabetes and chronic kidney disease (CKD), high-quality evidence about the relative benefits and harms of oral glucose-lowering drugs is limited.

Objective

To evaluate whether mortality risk differs after the initiation of monotherapy with either metformin or a sulfonylurea in Veterans with type 2 diabetes and CKD.

Design

Observational, national cohort study in the Veterans Health Administration (VHA).

Participants

Veterans who received care from the VHA for at least 1 year prior to initiating monotherapy treatment for type 2 diabetes with either metformin or a sulfonylurea between 2004 and 2009.

Main Measures

Metformin and sulfonylurea use was assessed from VHA electronic pharmacy records. The CKD-EPI equation was used to estimate glomerular filtration rate (eGFR). The outcome of death from January 1, 2004, through December 31, 2009, was assessed from VHA Vital Status files.

Key Results

Among 175,296 new users of metformin or a sulfonylurea monotherapy, 5121 deaths were observed. In primary analyses adjusted for all measured potential confounding factors, metformin monotherapy was associated with a lower mortality hazard ratio (HR) compared with sulfonylurea monotherapy across all ranges of eGFR evaluated (HR ranging from 0.59 to 0.80). A secondary analysis of mortality risk differences favored metformin across all eGFR ranges; the greatest risk difference was observed in the eGFR category 30–44 mL/min/1.73m² (12.1 fewer deaths/1000 person-years, 95% CI 5.2–19.0).

Conclusions

Initiation of metformin versus a sulfonylurea among individuals with type 2 diabetes and CKD was associated with a substantial reduction in mortality, in terms of both relative and absolute risk reduction. The largest absolute risk reduction was observed among individuals with moderately–severely reduced eGFR (30–44 mL/min/1.73m²).

     

Estimation of glomerular filtration rate from serum creatinine and cystatin C in octogenarians and nonagenarians

Background

Equations to estimate GFR have not been well validated in the elderly and may misclassify persons with chronic kidney disease (CKD). We measured GFR and compared the performance of the Modification of Diet in Renal Disease (MDRD), the Chronic Kidney Disease-Epidemiology Collaboration (CKD-Epi) and the Berlin Initiative Study (BIS) equations based on creatinine and/or cystatin C in octogenarians and nonagenarians.

Methods

Using cross-sectional analysis we assessed 95 very elderly persons (mean 85 years) living in the community. GFR was measured by iohexol (mGFR) and compared with estimates using six equations: MDRD, CKD-Epi_creatinine, CKD-Epi_cystatin, CKD-Epi_creatinine-cystatin, BIS_creatinine and BIS_creatinine-cystatin.

Results

Mean mGFR was 55 (range,19–86) ml/min/1.73 m². Bias was smaller with the CKD-Epi_creatinine-cystatin and the CKD-Epi_creatinine equations (-4.0 and 1.7 ml/min/1.73 m²). Accuracy (percentage of estimates within 30% of mGFR) was greater with the CKD-Epi_creatinine-cystatin, BIS_creatinine-cystatin and BIS_creatinine equations (85%, 83% and 80%, respectively). Among the creatinine-based equations, the BIS_creatinine had the greatest accuracy at mGFR?<?60 ml/min/1.73 m² and the CKD-Epi_creatinine was superior at higher GFRs (79% and 90%, respectively). The CKD-Epi_creatinine-cystatin, BIS_creatinine-cystatin and CKD-Epi_cystatin equations yielded the greatest areas under the receiver operating characteristic curve at GFR threshold?=?60 ml/min/1.73 m² (0.88, 0.88 and 0.87, respectively). In participants classified based on the BIS_creatinine, CKD-Epi_cystatin, or BIS_creatinine-cystatin equations, the CKD-Epi_creatinine-cystatin equation tended to improve CKD classification (net reclassification index: 12.7%, p?=?0.18; 6.7%, p?=?0.38; and 15.9%; p?=?0.08, respectively).

Conclusions

GFR-estimating equations CKD-Epi_creatinine-cystatin and BIS_creatinine-cystatin showed better accuracy than other equations using creatinine or cystatin C alone in very elderly persons. The CKD-Epi_creatinine-cystatin equation appears to be advantageous in CKD classification. If cystatin C is not available, both the BIS_cr equation and the CKD-Epi_cr equation could be used, although at mGFR?<?60 ml/min/1.73 m², the BIS_cr equation seems to be the best alternative.

     

MDRD vs. CKD-EPI in comparison to <Superscript>51</Superscript>Chromium EDTA: a cross sectional study of Malaysian CKD cohort

Background

Accurate measurement of renal function is important: however, radiolabelled gold standard measurement of GFR is highly expensive and can only be used on a very limited scale. We aim to compare the performance of Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations in the multi-ethnic population attending University Malaya Medical Centre (UMMC).

Methods

This is a cross-sectional study recruiting patients, who attend UMMC Nephrology clinics on voluntary basis. 51-Chromium EDTA (⁵¹Cr-EDTA) plasma level was used to measure the reference GFR. The serum creatinine was determined by IDMS reference modified Jaffe kinetic assay (Cr_Jaffe). The predictive capabilities of MDRD and CKD-EPI based equations were calculated. Data was analysed using SPSS version 20 and correlation, bias, precision and accuracy were determined.

Results

A total of 113 subjects with mean age of 58.12?±?14.76 years and BMI of 25.99?±?4.29 kg/m² were recruited. The mean reference GFR was 66.98?±?40.65 ml/min/1.73m², while the estimated GFR based on MDRD and CKD-EPI formula were 62.17?±?40.40, and 60.44?±?34.59, respectively. Both MDRD and CKD-EPI were well-correlated with reference GFR (0.806 and 0.867 respectively) and statistically significant with p?<?0.001. In the overall cohort, although MDRD had smaller bias than CKD-EPI (4.81 vs. 6.54), CKD-EPI was more precise (25.22 vs. 20.29) with higher accuracy within 30% of measured GFR (79.65 vs. 86.73%).

Conclusion

The CKD-EPI equation appeared to be more precise and accurate than the MDRD equation in estimating GFR in our cohort of multi-ethnic populations in Malaysia.

     

Different Peptic Ulcer Bleeding Risk in Chronic Kidney Disease and End-Stage Renal Disease Patients Receiving Different Dialysis

Background

End stage renal disease (ESRD) patients receiving hemodialysis (HD) have a higher risk of peptic ulcer bleeding (PUB).

Aims

Whether ESRD patients receiving peritoneal dialysis (PD) also carries a higher risk of PUB has not been studied.

Methods

This was a cohort study using Taiwan’s National Health Insurance research database, whereby 11,408 patients, including 2,239 PD, 2,328 HD, 2,267 chronic kidney disease (CKD) and 4,574 controls with age–sex matching were recruited. The log-rank test was used to analyze differences in accumulated PUB-free survival rates between groups. Cox proportional hazard regression was performed to evaluate independent risk factors for PUB in all the enrollees.

Results

During the 7-year follow-up, PD and CKD patients had a significantly higher rate of PUB than matched controls. The risk of PUB between PD and CKD was not significantly different. Moreover, patients receiving HD carried a higher risk of PUB than those receiving PD, with CKD and controls (p all <0.05, by log-rank test). Cox proportional hazard regression analysis showed that CKD (HR 3.99, 95 % CI 2.24–7.13), PD (HR 3.71, 95 % CI 2.00–6.87) and HD (HR 11.96, 95 % CI 7.04–20.31) were independently associated with an increased risk of PUB. Being elderly, male, having hypertension, diabetes, cirrhosis, and nonsteroidal anti-inflammatory drugs and steroid use were other independent risk factors of PUB in all enrollees.

Conclusions

Patients with CKD and ESRD receiving PD or HD carried a higher risk for PUB. They should be screened for risk factors for PUB and receive some protective measures to prevent PUB.

     

A Narrative Review on Thrombolytics in Advanced CKD: Is it an Evidence-Based Therapy?

Purpose

A timely pharmacoinvasive strategy consisting of thrombolytic therapy (TT) plays a pivotal role in three major scenarios: acute ischemic stroke (AIS), acute myocardial infarction (STEMI), and massive pulmonary embolism (PE). Presence of advanced chronic kidney disease (CKD) (estimated glomerular filtration rate <?30 mL/min/1.73 m2), known to disturb thrombotic/thrombolytic equilibrium, causes difficulties for clinicians in evaluating risk-benefit balance, as current guidelines do not address the relationship between TT and the advanced CKD. This narrative review aims to evaluate the most important scientific resources regarding the evidences, benefits, and risks of using thrombolytics in advanced CKD.

Methods

We searched the electronic database of PubMed for studies evaluating the relationship between renal dysfunction and TT in patients with STEMI, AIS, and massive PE. Randomized controlled trials (RCTs), observational studies including prospective or retrospective cohort studies, reviews, meta-analyses, and guidelines were included if referring to TT for one of the three scenarios in advanced CKD.

Results

Prothrombotic conditions in CKD, associated with an increased risk of hemorrhages, can affect the safety and efficacy of TT. Concerns regarding in-hospital bleeding events and poor clinical outcomes subsequent to TT in advanced CKD continue to cause underutilization or delaying routine reperfusion therapy.

Conclusions

The impact of TT on the outcomes of advanced CKD patients is poorly understood to date, with scarce data available in current guidelines and conflicting results from observational studies. Until evidence-based data from RCTs will be obtained, the clinical challenge of maximizing benefits for this high-risk subgroup lays in the hands of practicing clinicians.

     

Hypertension and the development of New onset chronic kidney disease over a 10 year period: a retrospective cohort study in a primary care setting in Malaysia

Background

Little is known about the rate of progression to chronic kidney disease (CKD) among hypertensive patients, particularly at the primary care level. This study aims to examine risk factors associated with new onset CKD among hypertensive patients attending a primary care clinic.

Methods

This is a 10-year retrospective cohort study of 460 patients with hypertension who were on treatment. Patient information was collected from patient records. CKD was defined as a glomerular filtration rate <60?ml/min per 1.73?m² (Cockcroft-Gault equation). Multiple logistic regression statistics was used to test the association in newly diagnosed CKD.

Results

The incidence of new CKD was 30.9% (n?=?142) with an annual rate of 3%. In multivariate logistic regression analysis, factors associated with development of new onset of CKD among hypertensive patients were older age (odds ratio [OR] 1.123, 95% confidence interval [CI] 1.078-1.169), presence of diabetes (OR 2.621, 95% CI 1.490-4.608), lower baseline eGFR (OR 1.041, 95% CI 0.943-0.979) and baseline hyperuricaemia (OR 1.004, 95% CI 1.001-1.007).

Conclusions

The progression to new onset CKD is high among urban multiethnic hypertensive patients in a primary care population. Hence every effort is needed to detect the presence of new onset CKD earlier. Hypertensive patients who are older, with underlying diabetes, hyperuricaemia and lower baseline eGFR are associated with the development of CKD in this population.

     

Diabetes und Nieren

Incidence of diabetic kidney diseases

In some European countries the incidence of end-stage renal disease (ESRD) has remained relatively constant or even fallen over the past years despite an increasing prevalence of chronic kidney diseases (CKD). This possibly indicates an improvement in long-term treatment; however, by 2015 a further increase in the prevalence of CKD is expected.

Diagnostics

In the diagnostics, the micro-ribonucleic acids (μRNA) have reached the stage of clinical trials. Among the many other suggestions for new biomarkers urinary podocalyxin and angiotensinogen appear to show promise.

Renin-angiotensin-aldosterone blockade

On the subject of simple versus dual renin-angiotensin-aldosterone (RAAS) blockade important meta-analyses were published, that levelled the problems of hyperkalemia and acute renal failure for dual blockade. Surprisingly, in a new meta-analysis no single antihypertensive agent could effectively influence the overall mortality of diabetes patients with diabetic nephropathy. In particular, the onset of ESRD was significantly delayed by dual RAAS blockade.

New substances: finerenone and patiromer

In a pilot study the new non-steroidal aldosterone antagonist finerenone showed a reduction in proteinuria without resulting in the known side effects of hyperkalemia and acute renal failure. The new oral potassium binder patiromer is suitable for long-term administration for the reduction of potassium and can effectively prevent the occurrence of hyperkalemia that occurred under conventional aldosterone antagonists.

     

A systematic review of central sleep apnea in adult patients with chronic kidney disease

Background

Obstructive sleep apnea has been widely studied in patients with chronic renal insufficiency; however only a limited number of studies have reviewed the association between central sleep apnea (CSA) and chronic kidney disease (CKD). The objectives of this systematic review were to assess the prevalence of CSA in and its association with CKD in adult patients and to determine if inclusion of the central hypopnea index affected the reported rates for the prevalence of CSA in CKD.

Methods

Medline, Web of Science, Google Scholar, Scopus, and Cochrane Library were searched through October 2015 without any language limitations.

Results

Of 188 articles searched, 8 articles met our study inclusion criteria. Of a cumulative total of 313 patients with CKD undergoing sleep study, a total of 30 patients were diagnosed with central sleep apnea. Three studies had patients with coexistent congestive heart failure, six studies included some patients on dialysis and at least 3 studies included central hypopneas while calculating central sleep apnea index.

Conclusion

The aggregate point prevalence of CSA in CKD is 9.6 %, although the estimated range is highly variable between 0 and 75 %. Limited evidence suggested that even after adjustment for cardiovascular comorbidities, CKD is independently associated with CSA. It is unknown if patients on dialysis are at increased risk compared to patients without end-stage renal disease. Standardization of polysomnographic criteria used to define CSA and sleep disordered breathing (SDB) as well as inclusion of central hypopneas in the overall CSA index will limit the heterogeneity and allow better estimation of the prevalence of CSA in patients with CKD.

     

Cardiorenal Interactions Revisited: How to Improve Heart Failure Outcomes in Patients With Chronic Kidney Disease

Purpose of the Review

To summarize current advances in the understanding and management of heart failure (HF) in patients with advanced chronic kidney disease (CKD).

Recent Findings

Diagnosis of HF and treatment of congestion are crucial in the management of patients with advanced CKD to reduce symptoms, preserve organ function, and improve outcomes. Echocardiography and cardiovascular biomarkers may help to differentiate cardiac from non-cardiac components of overhydration. Renal replacement therapy or ultrafiltration may be required to treat congestion. Furthermore, patients with advanced CKD are frequently undertreated with disease-modifying HF therapies, but the use of beta-blockers and ACEi should be considered under close monitoring of kidney function and serum potassium. The use of the new oral potassium binders may translate into improved outcomes.

Summary

The treatment of HF in patients with advanced CKD requires a multi-disciplinary approach. New diagnostic and therapeutic strategies are under evaluation and may contribute to improved outcomes.

     

Does Altered Uric Acid Metabolism Contribute to Diabetic Kidney Disease Pathophysiology?

Purpose of Review

Multiple experimental and clinical studies have identified pathways by which uric acid may facilitate the development and progression of chronic kidney disease (CKD) in people with diabetes. However, it remains uncertain if the association of uric acid with CKD represents a pathogenic effect or merely reflects renal impairment.

Recent Findings

In contrast to many published reports, a recent Mendelian randomization study did not identify a causal link between uric acid and CKD in people with type 1 diabetes. Two recent multicenter randomized control trials, Preventing Early Renal Function Loss in Diabetes (PERL) and FEbuxostat versus placebo rAndomized controlled Trial regarding reduced renal function in patients with Hyperuricemia complicated by chRonic kidney disease stage 3 (FEATHER), were recently designed to assess if uric acid lowering slows progression of CKD.

Summary

We review the evidence supporting a role for uric acid in the pathogenesis of CKD in people with diabetes and the putative benefits of uric acid lowering.