Increasing Chronic Kidney Disease Stage Research Articles

Risk Factors for Kidney Disease in Hb SC and Hb Sβ+-Thalassemia Sickle Cell Disease

Sickle cells disease (SCD) is an inherited red blood disorder that leads to acute and chronic organ complications. The kidneys are among the most commonly affected organ systems and chronic kidney disease (CKD) predicts increased morbidity and early mortality in SCD (PMID 1892333). Risk factors for CKD have been primarily investigated in patients with homozygous inheritance of the hemoglobin (Hb) S mutation but are not as well understood in other SCD variants, such as in those with Hb SC or Hb SB+-thalassemia. We investigated clinical, laboratory, and genetic predictors (α-thalassemia and the APOL1 G1 and G2 kidney disease risk variants) for CKD in a combined analysis of non-Hb SS patients from the University of Illinois at Chicago and the multi-center Walk-PHaSST cohort. Clinical and laboratory variables were obtained at the time of enrolment. Estimated glomerular filtration (eGFR) rate was calculated using the CKD-EPI formula and CKD stage was defined according to the KDIGO guidelines. Univariate analysis for the association of variables with eGFR, albuminuria, and CKD stage were conducted using the linear trend test and Cochran's test for linear trend. Variables with a P < 0.1 were entered into linear and ordinal logistic regression models adjusting for age and sex. Median and interquartile ranges (IQR) are provided. Two hundred and forty-seven patients were included in this analysis. The median age of this cohort was 39 years (IQR, 24 - 50 years), 62% were female, 16% were on hydroxyurea, and 72% were Hb SC genotype. Albuminuria data was available in 174 patients; microalbuminuria (albuminuria 30 - 300 mg/g creatinine) was present in 24% and macroalbuminuria (albuminuria > 300 mg/g creatinine) in 5% of patients. Patients with higher urine albumin concentration were older, had higher systolic blood pressures and LDH concentrations, and lower hemoglobin concentrations (P ≤ 0.03). On multivariate analysis, the urine albumin concentration was independently associated with a higher systolic blood pressure (log transformed β +3.08 ± 1.09; P = 0.005) and a lower hemoglobin concentration (β -0.17 ± 0.09; P = 0.05). Patients with lower eGFR were older, had higher body mass indexes and systolic blood pressures, lower hemoglobin concentrations, and were more frequently female (P ≤ 0.04). No variables were independently associated with eGFR on multivariate analysis after adjusting for age and sex. When applying the KDIGO CKD staging criteria, 67% were classified as not having CKD (urine albumin < 30mg/g creatinine and eGFR > 60 mL/min/1.73m2), 23% had stage 1 or 2 CKD (urine albumin ≥ 30mg/g creatinine and eGFR > 60 mL/min/1.73m2), and 10% had stage 3 or greater CKD (eGFR < 60 mL/min/1.73m2). Patients with increasing CKD stage were older, had higher systolic blood pressures and LDH concentrations, and lower hemoglobin concentrations (Table 1) (P ≤ 0.005). On multivariate analysis, incremental CKD stage was independently associated with lower hemoglobin (OR 0.91, 95%CI: 0.88 - 0.94; P = 0.002) and higher LDH (natural log OR 1.43, 95% CI: 1.27 - 1.61; P = 0.004) concentrations. We did not observe an association between coinheritance of α-thalassemia or the APOL1 G1/G2 risk variants with urine albumin concentration, eGFR, or CKD stage. In conclusion, we demonstrate that CKD is a common comorbidity that is observed in approximately one third of SCD patients with the Hb SC or Hb Sβ+-thalassemia genotypes. A lower hemoglobin concentration and higher systolic blood pressure were independently associated with greater urine albumin concentration. This may reflect anemia causing reduced oxygen delivery to the renal cortex and hypertension-mediated vascular and glomerular damage. The association of worsening CKD stage with lower hemoglobin and higher LDH concentrations, consistent with increased hemolysis, is similar to what has been observed in the Hb SS genotypes. The potential effects of hemolysis on kidney function in the Hb SC and Sβ+-thalassemia genotypes will need to be explored further. Disclosures Gladwin: Bayer Pharmaceuticals: Other: Co-investigator; United Therapeutics: Patents & Royalties: Co-inventor on an NIH government patent for the use of nitrite salts in cardiovascular diseases ; Globin Solutions, Inc: Patents & Royalties: Provisional patents for the use of recombinant neuroglobin and heme-based molecules as antidotes for CO poisoning. Gordeuk:Novartis: Consultancy, Honoraria, Research Funding; Global Blood Therapeutics: Consultancy, Honoraria, Research Funding; Emmaus: Consultancy, Honoraria; Modus Therapeutics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Research Funding; Modus Therapeutics: Consultancy, Honoraria; Pfizer: Research Funding; Inctye: Research Funding; Inctye: Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Ironwood: Research Funding; Ironwood: Research Funding; Imara: Research Funding; Imara: Research Funding. Saraf:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding.

SAT-211 SERUM ADIPOCYTE FATTY ACID BINDING PROTEIN LEVEL IS POSITIVELY ASSOCIATED WITH AORTIC ARTERIAL STIFFNESS IN CHRONIC KIDNEY DISEASE PATIENTS

The adipocyte-fatty-acid-binding protein (A-FABP) plays a crucial role in development of insulin resistance and atherosclerosis by the interaction of metabolic and inflammatory pathways in adipocytes and macrophages. Chronic kidney disease (CKD) accelerates atherosclerosis via augmentation of inflammation, perturbation of lipid metabolism, and other mechanisms. The aim of this study was to evaluate the relationship between serum A-FABP levels and carotid-femoral pulse wave velocity (cfPWV) values in patients with CKD. Fasting blood samples and baseline characteristics were obtained from 270 patients with CKD (stage 1-5). Serum A-FABP concentrations were determined by enzyme immunoassay kit. High aortic stiffness was defined as carotid-femoral pulse wave velocity (cfPWV) values >10 m/s according to the ESH-ESC 2013 guidelines. Among 270 CKD patients, 92 patients (34.1%) were in the high aortic stiffness group. When compared to those in the low aortic stiffness group, the high aortic stiffness group had high prevalence of diabetes mellitus (P = 0.004), older age (P < 0.001), higher waist circumference (P = 0.004), body fat mass (P = 0.010), systolic blood pressure (P < 0.001), fasting glucose (P = 0.014), blood urea nitrogen (P = 0.009), creatinine (P = 0.004), and higher serum A-FABP level (P < 0.001), while lower estimated glomerular filtration rate (P = 0.001). Multivariable logistic regression analysis of the factors significantly associated with aortic stiffness revealed that A-FABP levels (odds ratio (OR): 1.174, 95% confidence interval (CI): 1.047–1.317, P = 0.006), age (OR: 1.062, 95% CI: 1.033–1.092, P = 0.001), and systolic blood pressure (OR: 1.017, 95% CI: 1.003–1.031, P = 0.015) were the independent predictors of aortic stiffness in CKD patients. Multivariable forward stepwise linear regression analysis also showed that A-FABP level (β = 0.178, P = 0.001) was an independent predictor of cfPWV values in CKD patients. There were significant increases in cfPWV values (P = 0.001) and serum A-FABP levels (P < 0.001) across increasing CKD stages. Elevated A-FABP concentration could be a predictor for aortic stiffness in patients with CKD. Increased CKD stages will elevate in cfPWV values and serum A-FABP levels.

Association of blood pressure with clinical outcomes in older adults with chronic kidney disease.

Backgroundin chronic kidney disease (CKD), hypertension is associated with poor outcomes at ages <70 years. At older ages, this association is unclear. We tested 10-year mortality and cardiovascular outcomes by clinical systolic blood pressure (SBP) in older CKD Stages 3 and 4 patients without diabetes or proteinuria.Methodsretrospective cohort in population representative primary care electronic medical records linked to hospital data from the UK. CKD staged by CKD-EPI equation (≥2 creatinine measurements ≥90 days apart). SBPs were 3-year medians before baseline, with mean follow-up 5.7 years. Cox competing models accounted for mortality.Resultsabout 158,713 subjects with CKD3 and 6,611 with CKD4 met inclusion criteria. Mortality increased with increasing CKD stage in all subjects aged >60. In the 70 plus group with SBPs 140–169 mmHg, there was no increase in mortality, versus SBP 130–139. Similarly, SBPs 140–169 mmHg were not associated with increased incident heart failure, stroke or myocardial infarctions. SBPs <120 mmHg were associated with increased mortality and cardiovascular risk. At ages 60–69, there was increased mortality at SBP <120 and SBP >150 mmHg.Results were little altered after excluding those with declining SBPs during 5 years before baseline, or for longer-term outcomes (5–10 years after baseline).Conclusionsin older primary care patients, CKD3 or 4 was the dominant outcome predictor. SBP 140–169 mmHg having little additional predictive value, <120 mmHg was associated with increased mortality. Prospective studies of representative older adults with CKD are required to establish optimum BP targets.

Treatment Patterns in Type 2 Diabetes Patients with Chronic Kidney Disease-A Cohort Study

Introduction: The prevalence of type 2 diabetes mellitus (T2DM) is increasing in the U.S. and 40% of affected people develop chronic kidney disease (CKD). This study evaluated patients’ treatment patterns, disease burden and progression. Methods: This retrospective study used the U.S. claims database PharMetrics Plus (January 2006-December 2015) and the Experian consumer data asset (January 2007-December 2015) to evaluate longitudinal treatment patterns in patients with T2DM and CKD using ICD codes. In addition, CKD progression, all-cause mortality rate, clinical events and health care costs were described. Results: Of 250,742 patients identified, the median age was 61 years, 58% were male, 73% were Caucasian and 87% had hypertension. Proportions of patients using angiotensin II receptor blockers (ARB) or angiotensin-converting-enzyme inhibitors (ACEi) was lower in CKD stages 4 and 5 (54 and 52%, respectively) than in stages 1-3 (66-70%). The use of beta blockers (32-52%), calcium channel blockers (27-41%) and diuretics (37-54%) tended to increase from CKD stages 1 to 4 and decreased in stage 5. Antidiabetic drugs were prescribed to 65.7% of patients and their use decreased with increasing CKD stage. Of the 21% of patients who progressed within a year to a more severe CKD stage, the highest proportion advanced from stage 4 to 5 (42%). The most common clinical events were diabetic retinopathy, heart failure and acute kidney injury reported in 27%, 22% and 22% of patients, respectively. Overall, 4.6% died with a median time from index to death of 12.3 months. The annual health care costs of $46,028 per person included $9,103 and $36,925 for pharmacy and medical costs, respectively. Conclusions: The treatment of T2DM patients with CKD was mostly in line with current guideline recommendations. However, only up to 70% of patients used ARB and ACEi, the first line treatments. In addition, 21% of patients progressed to a more severe CKD stage. These findings suggest a need for new treatment options in this population. Disclosure M. Blankenburg: None. C.P. Kovesdy: Consultant; Self; Abbott. Advisory Panel; Self; AbbVie Inc.. Consultant; Self; Bayer AG. Advisory Panel; Self; AstraZeneca. Consultant; Self; Sanofi Genzyme. Advisory Panel; Self; Amgen Inc.. Consultant; Self; Keryx. S. Eisenring: None. A. Fett: Consultant; Self; IQVIA. E.W. Schokker: None. J. Korn: None. A. Gay: Employee; Self; Bayer AG.

Death and Dialysis After Transcatheter Aortic Valve Replacement: An Analysis of the STS/ACC TVT Registry

ObjectivesThe authors sought to elucidate the true incidence of renal replacement therapy (RRT) after transcatheter aortic valve replacement (TAVR). BackgroundThere is a wide discrepancy in the reported rate of RRT after TAVR (1.4% to 40%). The true incidence of RRT after TAVR is unknown. MethodsThe STS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) registry was linked to the Centers for Medicare & Medicaid database to identify all patients that underwent TAVR from November 2011 through September 2015 and their outcomes. The authors compared rates of death, new RRT, and a composite of both as a function of pre-procedure glomerular filtration rate (GFR), both in stages of chronic kidney disease (CKD), as well as on a continuous scale. ResultsPre-procedure GFR is associated with the risk of death and new RRT after TAVR when GFR is <60 ml/min/m2, and increases significantly when GFR falls below 30 ml/min/m2. Incremental increases in GFR of 5 ml/min/m2 were statistically significant (unadjusted hazard ratio: 0.71; p < 0.001) at 30 days, and continued to be significant at 1 year when pre-procedure GFR was <60 ml/min/m2. One in 3 CKD stage 4 patients will be dead within 1 year, with 14.6% (roughly 1 in 6) requiring dialysis. In CKD stage 5, more than one-third of patients will require RRT within 30 days; nearly two-thirds will require RRT at 1 year. ConclusionsIn both unadjusted and adjusted analysis, pre-procedural GFR was associated with the outcomes of death and new RRT. Increasing CKD stage leads to an increased risk of death and/or RRT. Continuous analysis showed significant differences in outcomes in all levels of CKD when GFR was <60 ml/min/m2. Pre-procedure GFR should be considered when selecting CKD patients for TAVR.

Turnover of type III collagen reflects disease severity and is associated with progression and microinflammation in patients with IgA nephropathy.

Renal fibrosis is the hallmark of progression to end-stage kidney disease. Non-invasive biomarkers of renal fibrosis could serve as specific end points in clinical trials and improve monitoring and stratification of patients with chronic kidney disease (CKD). To address this, we measured markers of collagen type III turnover in urine and serum of IgA nephropathy (IgAN) patients. We measured the collagen type III pro-peptide (Pro-C3), representing production, and a neo-epitope fragment (C3M), representing a specific degradation fragment of collagen type III, in urine and serum samples from two cohorts of IgAN patients using newly developed enzyme-linked immunosorbent assays. With increasing CKD stage, urinary C3M gradually decreased (mean C3M/creatinine: 17.3 ng/mg in CKD stage 1, 3.5 ng/mg in CKD stage 5) whereas urinary Pro-C3 gradually increased (mean Pro-C3/creatinine: 4.1 ng/mg in CKD stage 1, 20.8 ng/mg in CKD stage 5). The urinary Pro-C3/C3M ratio, a measure of collagen type III turnover, significantly increased in advanced CKD stages. Serum C3M was not related to CKD stage but was associated with microinflammation. Urinary C3M was significantly lower in patients whose CKD stage subsequently progressed compared with those who did not progress. Our results suggest that the combination of urinary markers of collagen type III turnover, in particular the urinary Pro-C3/C3M ratio, is a potential novel, non-invasive diagnostic and prognostic tool to specifically monitor extracellular matrix (ECM) remodelling in kidney fibrosis.

Growth impairment in children with pre-dialysis chronic kidney disease in Japan.

Growth impairment is a major complication of chronic kidney disease (CKD) in children. However, no cohort studies have examined the growth of Asian children with pre-dialysis CKD. We sent cross-sectional surveys to 113 Japanese medical institutions that were treating 447 children with CKD stages 3-5 in 2010 and 2011. Of 447 children included in our survey conducted in 2010, height and CKD stage were evaluable for 297 children in 2011, and height standard deviation score (height SDS) was calculated in these children. Height SDS decreased with increasing CKD stage (P < 0.001) in boys and girls. Height SDS also decreased significantly with increasing CKD stage among patients with congenital anomalies of the kidney and urinary tract (P < 0.001). Risk factors for growth impairment included CKD stages 4 and 5 (relative to stage 3), being small-for-date, and asphyxia at birth. Among children with a height SDS ≤-2.0, growth hormone was used in 19.5, 31.0, and 25.0 % of children with CKD stages 3, 4, and 5, respectively. This prospective cohort study revealed marked growth impairment in Japanese children with CKD stages 3-5 relative to healthy children. CKD-related risk factors for growth impairment included advanced CKD (stages 4 and 5), being small-for-date, and asphyxia at birth. Growth hormone was infrequently used in this cohort of children with pre-dialysis CKD.

Microscopic nephrocalcinosis in chronic kidney disease patients.

Experimental data indicate that microscopic calcium phosphate deposition in the kidney (nephrocalcinosis) may accelerate progression of chronic kidney disease (CKD). Data on the prevalence, risk factors and implications of nephrocalcinosis in CKD patients are scarce. A mineral metabolism disorder could play an important pathogenetic role, as suggested by recent protocol biopsy findings in incident renal transplant recipients. Kidney biopsy cylinders of CKD patients, collected between January 1989 and December 2007, were screened for the presence of nephrocalcinosis. Only patients with ≥1 parathyroid hormone (PTH) level available within 180 days of the biopsy were eligible for inclusion (n = 211). Demographics and mineral metabolism parameters were retrieved from medical files. Data on renal death (up to December 2012) were obtained from the Flemish ESRD registry. Baseline biopsies from 110 deceased kidney transplant donors served as controls. The prevalence of nephrocalcinosis in kidney donors and patients with CKD 1-2, CKD 3-4 and CKD 5-5D was 4.6, 14.3, 20.2 and 54.0%, respectively (P < 0.0001). Among CKD patients, patients with nephrocalcinosis were characterized by lower estimated GFR, lower serum bicarbonate level and higher serum PTH and calcium level. In multivariate regression analysis, high serum PTH, calcium and creatinine level, and low serum bicarbonate level were all significantly and independently associated with nephrocalcinosis. Serum phosphorus level, but not nephrocalcinosis predicted renal death, independent of renal function. Our data demonstrate that prevalence rates of nephrocalcinosis increase with increasing CKD stage to reach more than 50% in end-stage renal disease patients and suggest that acid-base and mineral metabolism disturbances are implicated in its pathogenesis.

High uric acid level is a risk factor for progression of IgA nephropathy with chronic kidney disease stage G3a.

High uric acid level is a known risk factor for deterioration of renal function in chronic kidney disease (CKD), but its influence on the progression of IgA nephropathy (IgAN) remains unclear. Adult IgAN patients (n = 611) were classified according to CKD stage. Renal survival rates and clinical and histological findings were compared between patients with high (H-UA) and normal (N-UA) uric acid levels in different CKD stages. The proportion of patients with H-UA increased significantly with increasing CKD stage (stage G1, 12.3%; stage G2, 19.0%; stage G3a, 43.7%; stage G3b-4, 69.0%; P < 0.001). The 30-year renal survival rate was similar in patients with H-UA and N-UA in CKD stages G1, G2, and G3b-4, but was significantly lower in patients with H-UA than with N-UA in CKD stage G3a (24.7 vs. 51.9%; P = 0.0205). The clinical findings were similar in patients with H-UA and N-UA, but the interval from onset to biopsy differed between groups. The proportion of patients with global sclerosis was significantly higher in patients with H-UA than with N-UA in CKD stage G3a (33.3 vs. 11.4%; P = 0.0005), but the Oxford classifications were similar between groups. Multivariate Cox regression analysis identified H-UA (HR 1.36, 95% CI 1.07-1.72, P = 0.011) and a large amount of proteinuria (HR 1.38, 95% CI 1.09-1.74, P = 0.0084) as independent predictors of end-stage renal disease. H-UA induced global glomerular sclerosis and accelerated the progression of IgAN in CKD stage G3a.

The need for improved identification and accurate classification of stages 3-5 Chronic Kidney Disease in primary care: retrospective cohort study.

BackgroundAround ten percent of the population have been reported as having Chronic Kidney Disease (CKD), which is associated with increased cardiovascular mortality. Few previous studies have ascertained the chronicity of CKD. In the UK, a payment for performance (P4P) initiative incentivizes CKD (stages 3–5) recognition and management in primary care, but the impact of this has not been assessed.Methods and FindingsUsing data from 426 primary care practices (population 2,707,130), the age standardised prevalence of stages 3–5 CKD was identified using two consecutive estimated Glomerular Filtration Rates (eGFRs) seven days apart. Additionally the accuracy of practice CKD registers and the relationship between accurate identification of CKD and the achievement of P4P indicators was determined. Between 2005 and 2009, the prevalence of stages 3–5 CKD increased from 0.3% to 3.9%. In 2009, 30,440 patients (1.1% unadjusted) fulfilled biochemical criteria for CKD but were not on a practice CKD register (uncoded CKD) and 60,705 patients (2.2% unadjusted) were included on a practice CKD register but did not fulfil biochemical criteria (miscoded CKD). For patients with confirmed CKD, inclusion in a practice register was associated with increasing age, male sex, diabetes, hypertension, cardiovascular disease and increasing CKD stage (p<0.0001). Uncoded CKD patients compared to miscoded patients were less likely to achieve performance indicators for blood pressure (OR 0.84, 95% CI 0.82–0.86 p<0.001) or recorded albumin-creatinine ratio (OR 0.73, 0.70–0.76, p<0.001).ConclusionsThe prevalence of stages 3–5 CKD, using two laboratory reported eGFRs, was lower than estimates from previous studies. Clinically significant discrepancies were identified between biochemically defined CKD and appearance on practice registers, with misclassification associated with sub-optimal care for some people with CKD.

Serum levels of the myokine irisin in relation to metabolic and renal function

Irisin has recently been introduced as a novel myokine which reverses visceral obesity and improves glucose metabolism in mice. However, regulation of irisin in humans in relation to renal and metabolic disease has not been comprehensively studied. Serum irisin levels were quantified by ELISA and correlated with anthropometric and biochemical parameters of renal function, glucose and lipid metabolism, as well as inflammation, in 532 patients with stages 1-5 of chronic kidney disease (CKD). Median serum irisin levels adjusted for age, gender, and BMI significantly decreased with increasing CKD stage and lowest concentrations were seen in patients with CKD stage 5. Furthermore, irisin concentrations were associated with facets of the metabolic syndrome including diastolic blood pressure, markers of impaired glucose tolerance, and dyslipidemia in univariate analysis. Moreover, markers of renal function, e.g. glomerular filtration rate, and insulin resistance, e.g. homeostasis model assessment of insulin resistance, remained independently associated with circulating irisin levels in robust multivariate analysis. We show that irisin serum concentrations decrease with increasing CKD stage and are independently and positively predicted by renal function and insulin resistance. The physiological relevance of our findings, as well as the factors contributing to irisin regulation in humans, needs to be further defined in future experiments.

Impact of preexisting chronic kidney disease on acute and long-term outcome of critically ill patients on a medical intensive care unit

Chronic kidney disease (CKD) increases acute and long-term mortality of many diseases. Limited data are available, in how far a preexisting non-dialysis dependent CKD affects the outcome of critically ill patients treated for non-renal causes. In a retrospective study, we assessed the outcome of 524 patients with need for mechanical ventilation at our medical intensive care unit between 2002 and 2007. Patients were divided into 5 CKD stages depending on their calculated glomerular filtration rate at hospital admission excluding patients with pre-existing end-stage renal failure. In-hospital and long-term outcome up to 5years were assessed. Advanced stages of CKD at admission were associated with higher age (p<0.001) and diabetes (p=0.003). Patients with higher CKD stages suffered more often from acute renal failure (p<0.001), required longer renal replacement therapy (p<0.001) and more often in-hospital resuscitation (p=0.019). 405 patients died during follow-up (226 in-hospital). Multivariate Cox regression analysis identified eGFR as independent predictor of 30-day- (HRR 0.994, 95% CI 0.990-0.998) and 1-year-mortality (HRR 0.996, 95% CI 0.993-1.000). Long-term survival decreased significantly with increasing CKD stages (p=0.004) and occurrence of acute renal failure (p<0.001). In critically ill patients requiring mechanical ventilation, preexisting non-dialysis dependent CKD has marked impact on occurrence of acute renal failure, 30-day- and 1-year-mortality.

Cystatin C as an Early Marker of Diabetic Nephropathy in Patients with Type 2 Diabetes

Serum cystatin C has been proposed as an endogenous marker of glomerular filtration rate (GFR) because it shows a correlation with the albumin to creatinine ratio (ACR) in diabetic nephropathy. The aim of this study was to examine the usefulness of cystatin C as an early marker of diabetic nephropathy. From February 2010 to July 2010, 205 outpatients with normo- or microalbuminuria and chronic kidney disease (CKD) of stage III or less were included in this study. Various renal markers including serum cystatin C and ACR were evaluated. In the ROC curve analysis, cystatin C showed a performance similar to that of serum creatinine. In addition, cystatin C levels increased with increasing CKD stage I to III and from normo- to microalbuminuria and showed a positive correlation with ACR. In a comparison of renal function markers in diabetic patients according to serum cystatin C level, all markers including ACR, serum creatinine, and eGFR showed significant differences between patients with cystatin C level < 1.06 mg/L and those with cystatin C > or = 1.06 mg/L. Serum cystatin C is a useful marker of early renal impairment in type 2 diabetic patients because it reflects both a decrease in GFR and elevated ACR.

Age, eGFR, and CKD Complications

Age, eGFR, and CKD Complications

Serum High-Sensitivity Cardiac Troponin T Is a Significant Biomarker of Left-Ventricular Diastolic Dysfunction in Subjects with Non-Diabetic Chronic Kidney Disease

Background: Chronic kidney disease (CKD) is associated with left-ventricular (LV) diastolic dysfunction (LVDD) which progresses to diastolic heart failure. However, biomarkers predicting LVDD in patients with CKD are largely unknown. Methods: In 93 patients with non-diabetic CKD, the relationships among echocardiography, high-sensitivity cardiac troponin T (hs-cTnT), B-type natriuretic peptide (BNP), and renal function were evaluated. LV mass index, peak early diastolic mitral filling velocity (E), peak early diastolic mitral annular velocity (E′), and E/E′ were recorded. Results: The E′ values were significantly decreased and E/E′, BNP, and hs-cTnT increased with increasing CKD stage. The CKD patients with LVDD with E′ <5 cm/s had a significantly higher hs-cTnT level as well as a significantly higher BNP level compared to those with E′ ≧5 cm/s. The area under the receiver-operating characteristic curve for hs-cTnT and BNP to detect E′ <5 cm/s was 0.880 (p = 0.0101) and 0.741 (p = 0.0570), respectively. In multivariate analysis, hs-cTnT and albuminuria were significantly associated with E′, and estimated glomerular filtration rate with the hs-cTnT level, after adjusting for age, cause of CKD, and other parameters. Conclusions: These data suggest that hs-cTnT may be a useful biomarker of LVDD in non- diabetic CKD patients.

Changes in bone mineral parameters, vitamin D metabolites, and PTH measurements with varying chronic kidney disease stages

Vitamin D deficiency is associated with an increased risk of many diseases (skeletal and nonskeletal). Emerging data also associate high concentrations of serum parathyroid hormone (PTH) with morbidity and increased mortality in patients both with and without known chronic kidney disease (CKD). Understanding the relationship between vitamin D and PTH and the determinants of PTH is therefore important. We performed a cross-sectional study of 203 patients with varying stages of CKD randomly recruited from the Renal Unit database at our institution. Detailed case review was performed, and samples of fasting blood were taken for biochemical analyses. We measured standard biochemistry, 25-hydroxyvitamin D (25-OHD), 1,25-OHD, and three PTH measurements [1-84 PTH, total PTH, and derived N-terminal truncated, 7-84 PTH (cPTH)]. Vitamin D deficiency was high, with 86% of patients having 25-OHD levels below 30ng/ml. Estimated glomerular filtration rate (eGFR) was not associated with 25-OHD levels, whereas 1,25-OHD was lower in those with CKD stage 5 versus stage 4, who were not treated with vitamin D metabolites (18 vs. 65pg/ml, respectively; P<0.05). All three PTH measurements increased with worsening eGFR, with this finding being more pronounced in those patients who were not treated with vitamin D metabolites. The slope of the regression line of cPTH on eGFR tended to be steeper, -0.90, compared to -0.81 for total PTH and -0.80 for 1-84 PTH (P=0.06). The ratio of total PTH to cPTH did decrease significantly through the range of CKD stages (P=0.03). The determinants of PTH were similar for all three PTH measurements, with eGFR having a strong inverse relationship, with weaker relationships for 25-OHD and ionized calcium on multivariate analyses. We confirm that there is a complex relationship between 25-OHD, eGFR, and PTH. Total PTH, 1-84 PTH, and cPTH increase with increasing CKD stages, with a relatively greater increase in cPTH, although the clinical significance of this finding remains uncertain. The three PTH measurements had similar correlations with the biochemical and clinical variables studied, suggesting that either total PTH or 1-84 PTH can be used in clinical practice when evaluating vitamin D and PTH status.

Anemia and Risk of Hospitalization in Pediatric Chronic Kidney Disease

Anemia is a well known complication of chronic kidney disease (CKD); however, the prevalence of anemia within CKD stages in the pediatric population has not been established. Additionally, the associated morbidity of anemia in the pediatric CKD population has not been elucidated. 2,779 patients ages 2 yr and older in the North American Pediatric Renal Trials and Collaborative Studies database with CKD stage II to V (excluding dialysis or previous transplant patients) were identified. Descriptive statistics and multivariate modeling using logistic regression was performed to determine the prevalence of anemia and to evaluate the correlation between baseline anemia and hospitalization. The prevalence of anemia (hematocrit < 33%) increased from 18.5% in CKD stage II to 68% in CKD stage V (predialysis). Anemic children were 55% more likely to be hospitalized when compared with nonanemic children (odds ratio 1.55; 95% confidence interval 1.23 to 1.94). Similar results were obtained using hematocrit cutoffs of 36 and 39%. In this pediatric predialysis CKD population, anemia increases with increasing CKD stage and is significantly associated with hospitalization risk. Hematocrit levels above 36 and 39% were not associated with increased risk of hospitalization. Further examination into the effect of correcting anemia on hospitalization rates may provide additional useful information.

Quantitative Assessment of Serum and Urinary Polyclonal Free Light Chains in Patients with Chronic Kidney Disease

Monoclonal free light chains (FLC) frequently cause kidney disease in patients with plasma cell dyscrasias. Polyclonal FLC, however, have not been assessed in patients with chronic kidney disease (CKD) yet could potentially play an important pathologic role. This study describes for the first time polyclonal FLC in patients with CKD. A sensitive, quantitative immunoassay was used to analyze serum and urinary polyclonal FLC in 688 patients with CKD of various causes. Serum kappa and lambda FLC concentrations increased progressively with CKD stage (both P < 0.001) and strongly correlated with markers of renal function, including cystatin-C (kappa: R = 0.8, P < 0.01; and lambda: R = 0.79, P < 0.01). Urinary FLC concentrations varied significantly between disease groups (kappa: P < 0.001; lambda: P < 0.005) and also rose significantly with increasing CKD stage (both FLC P < 0.0001). Urinary FLC concentrations were positively correlated with their corresponding serum concentration (kappa: R = 0.63; lambda: R = 0.65; both P < 0.001) and urinary albumin creatinine ratio (kappa: R = 0.58; lambda: R = 0.65; both P < 0.001). The proportion of patients with abnormally high urinary FLC concentrations rose with both the CKD stage and the severity of albuminuria. This study demonstrates significant abnormalities of serum and urinary polyclonal FLC in patients with CKD. These data provide the basis for studies that assess the contribution of polyclonal FLC to progressive renal injury and systemic inflammation in patients with kidney disease.

Chronic Renal Failure in Kidney Transplant Recipients. Do They Receive Optimum Care?: Data from the UK Renal Registry

We report the prevalence of chronic kidney disease (CKD) and related complications in a national cohort of RTR (n=9542), and compare this with dialysis patients. The majority of RTR were classified as having CKD stage 2T (21.6%) or 3T (57.5%) with 15.7% classified as CKD stage 4T and 3.1% as stage 5T. Only 2.1% of RTR were in CKD stage 1T. The proportion of patients with stage 4T and 5T CKD who lost their graft in the following year was 8% and 49%, respectively. The prevalence of anemia (hemoglobin <11 g/dL) increased from 4.4% in stage 1T to 51.5% in stage 5T and compared with 30% in dialysis patients (p<0.0001). Hypertension, hyperphosphatemia, elevated Ca x PO(4), raised iPTH and hypoalbuminemia rose with increasing CKD stage. For many variables, the achievement of standards was lower in stage 5T RTR than in dialysis patients. There were center differences in median estimated glomerular filtration rate and percentage of patients with hemoglobin <11 g/dL (p<0.0001). In conclusion, many patients in stage 4T-5T have CKD-related complications that fall below targets established for nontransplant CKD patients. They are at increased risk of graft loss. More attention needs to be paid to managing these complications and preparing these patients for a return to dialysis and/or retransplantation.

An Address on the Therapeutics of the Uric Acid Diathesis

<h3>Abstract</h3> <h3>Background</h3> Chronic kidney disease (CKD) is associated with an increased risk for cardiovascular events, hospitalizations or mortality. In populations aged ≥40 years, CKD is as prevalent as diabetes or coronary heart disease. Awareness for CKD though is generally low in public, patients and physicians, which hinders early diagnosis and treatment to decelerate disease progress. <h3>Method</h3> We analyzed baseline data collected in 2010 from 3,334 participants with CKD stages 1-5 from German CKD cohorts and registries. CKD unawareness and 95%-confidence intervals (CI) was estimated according to patients’ answer to the question whether they had ever been told to suffer from a CKD. Prevalence ratios (PR) with 95%-CI were estimated in categories of age, sex, CKD stages, BMI, hypertension, diabetes and other relevant comorbidities. <h3>Results</h3> CKD unawareness was high, reaching 82% (95% CI: 80%-84%) for CKD stages 1 or 2, 71% (68%-73%) in CKD 3a, 49% (45%-54%) in CKD 3b and still 30% (24%-36%) in CKD4, in each stage increasing with age. CKD unawareness was similarly high in patients with hypertension, diabetes or cardiovascular comorbidities. Women were more often unaware than men (PR=1.07 (1.02;1.12)), this sex difference increased with increasing CKD stage. Macroalbuminuria (PR=0.90 (0.82; 1.00)), anemia (PR=0.78 (0.73; 0.83)) and BMI ≥40 (PR=0.88 (0.77; 1.00)) were associated with higher CKD awareness. <h3>Conclusion</h3> Even in older patients or in patients with comorbidities, CKD unawareness was high. Sex differences were largest in later stages. Guideline oriented treatment of patients with hypertension or diabetes could increase awareness. Patient-physician communication about CKD might be amendable.