The impact on incident tuberculosis by kidney function impairment status: analysis of severity relationship.

BACKGROUND: The risk of tuberculosis (TB) in patients with impaired kidney function remains unclear by different stages of renal function impairment. METHODS: We retrospectively recruited all patients with kidney function in a tertiary-care referral center from January 2008 to December 2013 and followed them till December 2016. We defined the primary outcome as active TB development and analyzed the impact of kidney function impairment. RESULTS: During the study period, a total of 289,579 patients were enrolled for analysis, and of them, 1012 patients had active TB events in an average of 4.13 years of follow-up. According to kidney function impairment, the incidence rate of TB was similar in patients with no chronic kidney disease (CKD) or stage 1 and stage 2, and it increased apparently at stage 3a (167.68 per 100,000 person-years) to stage 3b, stage 4 and stage 5 (229.25, 304.95 and 349.29 per 100,000 person-years, respectively). In a Cox proportional hazard regression model, the dose response of TB risk among different stages of kidney function impairment increased significantly from CKD stage 3a to stage 5. Patients with long-term dialysis had a hazard ratio of 2.041 (1.092-3.815, p = 0.0254), which is similar to that of stage 4 CKD but lower than that of stage 5. CONCLUSION: In patients with impaired kidney function, the risk of TB increases from CKD stage 3, and in stage 5, the risk is even higher than that of those receiving dialysis. Further strategies of TB control need to consider this high-risk group.

Reduction in the Doses of Direct Oral Anticoagulants and Risk of Ischemic Stroke Events: A Hospital Survey.

Inappropriately reduced doses (IRDs) of direct oral anticoagulants (DOACs) are common in clinical practice. We performed a retrospective review using electronic medical records of St. Marianna University School of Medicine Hospital (a 1200-bed teaching hospital in Japan) to address the prevalence of IRDs and patient-related factors that result in IRDs. We also surveyed DOAC-treated patients who were hospitalized due to a stroke during the 5-year study period to analyze the association between stroke events and IRDs. We found that one in five patients who were newly prescribed a DOAC was treated with IRDs. Patients treated with edoxaban received the most IRDs (64%, 7/11), followed by those treated with dabigatran (50%, 1/2), apixaban (32%, 19/61), and rivaroxaban (27%, 12/44). Our analysis showed that the renal function (measured as serum creatinine and creatinine clearance values) and age are possible factors influencing dose reduction. The HAS-BLED score and antiplatelet use were not associated with IRD prescription. An analysis of the 5-year hospital records revealed 20 stroke cases despite ongoing treatments with DOACs, and IRDs were noted in three of these cases. In all three cases, the patients had been on an IRD of rivaroxaban. To prevent IRDs of DOACs, we suggest that a clinical protocol be incorporated into formularies to support the prescription process.

Utility of Urine Neutrophil Gelatinase-Associated Lipocalin for Worsening Renal Function during Hospitalization for Acute Heart Failure: Primary Findings of the Urine N-gal Acute Kidney Injury N-gal Evaluation of Symptomatic Heart Failure Study (AKINESIS).

BACKGROUND: Worsening renal function (WRF) during acute heart failure (AHF) occurs frequently and has been associated with adverse outcomes, though this association has been questioned. WRF is now evaluated by function and injury. We evaluated whether urine neutrophil gelatinase-associated lipocalin (uNGAL) is superior to creatinine for prediction and prognosis of WRF in patients with AHF. METHODS AND RESULTS: We performed a multicenter, international, prospective cohort of patients with AHF requiring IV diuretics. The primary outcome was whether uNGAL predicted development of WRF, defined as a sustained increase in creatinine of 0.5 mg/dL or ≥50% above first value or initiation of renal replacement therapy, within the first 5 days. The main secondary outcome was a composite of in-hospital adverse events. We enrolled 927 patients (mean 68.5 years of age, 62% men). The primary outcome occurred in 72 patients (7.8%). The first, peak and the ratio of uNGAL to urine creatinine (area under curves (AUC) ≤ 0.613) did not have diagnostic utility over the first creatinine (AUC 0.662). There were 235 adverse events in 144 patients. uNGAL did not predict (AUCs ≤ 0.647) adverse clinical events better than creatinine (AUC 0.695). CONCLUSIONS: uNGAL was not superior to creatinine for predicting WRF or adverse in-hospital outcomes and cannot be recommended for WRF in AHF.

A Fast Decline of Residual Renal Function in the First Year is a Predictor for Early Withdrawal from Peritoneal Dialysis in Non-Diabetic Patients.

BACKGROUND/AIMS: Little is known about the relationship between residual renal function (RRF) decline in early period and survival in non-diabetic peritoneal dialysis (PD) patients. METHODS: A total of 567 non-diabetic patients who began PD from January 1, 2005 to June 30, 2013 was investigated. The rate of RRF decline was determined by the "slope of the trend equation" of serial RRFs. A composite end-point of all-cause mortality and conversion to hemodialysis (HD) was used, survival status was censored on June 30, 2016. RESULTS: The median of "the slope of RRF decline equation" was 0.308 (0.001-2.111) ml/min/1.73 m2/ month. In the median follow-up period of 43 months (range 12 to 120 months), 65 (11.5%) patients died, 90 (15.9%) patients converted to HD and 171 (30.2%) patients received kidney transplantation. Multivariate linear regression showed male, high baseline RRF, high baseline peritoneal Kt/V urea, low serum albumin and low uric acid were independently associated with the rate of RRF decline in the first year of PD. Multivariate Cox models revealed that RRF decline in the first year remained a predictor for composite end-point (HR, 2.74, 95% CI, 1.53 to 4.90, P=0.001). The patients were divided into high RRF decline group (> 0.308ml/ min/1.73m2/month) and low RRF decline group (≤0.308 ml/min/1.73m2/month). In the first three years of PD, the rate of end-point events was higher in high RRF decline group (23.2%) than that in low RRF decline group (11.0%) (P< 0.001). There were 189 patients in low RRF decline group and 171 patients in high RRF decline group maintaining PD for more than 3 years, in a median follow-up of 54 months (range 37 to 120 months), the survival rate was 30.9% in high RRF decline group and 46.4% in low RRF decline group (P=0.883). In high RRF decline group, there were 92 patients reaching composited end-point and 112 patients maintaining PD; multivariate Cox model showed high peritoneal Kt/V urea after 1 year of PD and high albumin level were protective factors (HR, 0.29, 95% CI, 0.13 to 0.61, P= 0.001; HR, 0.94, 95% CI, 0.90-0.99, P=0.022, respectively), while fast RRF decline remained risk factor for composite end-point (HR, 3.28, 95% CI,1.48-7.31, P=0.004). CONCLUSION: A faster RRF decline in the first year was a predictor for all-cause mortality and conversion to HD in non-diabetic PD patients, mainly in the first three year. For patients with faster RRF decline, increasing PD dose was effective to improve survival.

Blood Lead Levels and Decreased Kidney Function in a Population-Based Cohort.

BACKGROUND: Environmental lead exposure has been associated with decreased kidney function, but evidence from large prospective cohort studies examining low exposure levels is scarce. We assessed the association of low levels of lead exposure with kidney function and kidney disease. STUDY DESIGN: Prospective population-based cohort. SETTING & PARTICIPANTS: 4,341 individuals aged 46 to 67 years enrolled into the Malmö Diet and Cancer Study-Cardiovascular Cohort (1991-1994) and 2,567 individuals subsequently followed up (2007-2012). PREDICTOR: Blood lead concentrations in quartiles (Q1-Q4) at baseline. OUTCOMES: Change in estimated glomerular filtration rate (eGFR) between the baseline and follow-up visit based on serum creatinine level alone or in combination with cystatin C level. Chronic kidney disease (CKD) incidence (185 cases) through 2013 detected using a national registry. MEASUREMENTS: Multivariable-adjusted linear regression models to assess associations between lead levels and eGFRs at baseline and follow-up and change in eGFRs over time. Cox regression was used to examine associations between lead levels and CKD incidence. Validation of 100 randomly selected CKD cases showed very good agreement between registry data and medical records and laboratory data. RESULTS: At baseline, 60% of study participants were women, mean age was 57 years, and median lead level was 25 (range, 1.5-258) µg/L. After a mean of 16 years of follow-up, eGFR decreased on average by 6mL/min/1.73m2 (based on creatinine) and 24mL/min/1.73m2 (based on a combined creatinine and cystatin C equation). eGFR change was higher in Q3 and Q4 of blood lead levels compared with Q1 (P for trend = 0.001). The HR for incident CKD in Q4 was 1.49 (95% CI, 1.07-2.08) compared with Q1 to Q3 combined. LIMITATIONS: Lead level measured only at baseline, moderate number of CKD cases, potential unmeasured confounding. CONCLUSIONS: Low-level lead exposure was associated with decreased kidney function and incident CKD. Our findings suggest lead nephrotoxicity even at low levels of exposure.

Residual renal function in chronic dialysis is not associated with reduced erythropoietin-stimulating agent dose requirements: a cross-sectional study.

BACKGROUND: Anaemia is a very common problem in patients with end-stage kidney disease (ESKD) and the use of erythropoietin-stimulating agents (ESA) has revolutionised its treatment. Residual renal function (RRF) is associated with a reduction in ESA resistance and mortality in chronic dialysis. The primary aim was to establish whether RRF has an association with ESA dose requirements in ESKD patients receiving chronic dialysis. METHODS: A single center, cross-sectional study involving 100 chronic dialysis patients was conducted from December 2015 to May 2016. Participants were divided into two groups depending on presence of RRF, which was defined as a 24-h urine sample volume of ≥ 100 ml. Erythropoietin resistance index [ERI = total weekly ESA dose (IU)/weight (kg)/haemoglobin concentration (g/dL] was used as a measure of ESA dose requirements. RESULTS: There was no difference in ERI between those with RRF as compared to those without (9.5 versus 11.0, respectively; P = 0.45). Also, ERI did not differ between those receiving haemodialysis as compared with peritoneal dialysis (10.8 versus 10.2, respectively; P = 0.84) or in those using renin-angiotensin system (RAS) blockers as compared with no RAS blocker use (11.6 versus 9.2, respectively; P = 0.10). Lower ERI was evident for those with cystic kidney disease as compared to those with other causes of ESKD (6.9 versus 16.5, respectively; P = 0.32) although this did not reach statistical significance. Higher ERI was found in those with evidence of systemic inflammation as compared to those without (16.5 versus 9.5, respectively; P = 0.003). CONCLUSIONS: There was no association between RRF and ESA dose requirements, irrespective of dialysis modality, RAS blocker use, primary renal disease or hyperparathyroidism.

White blood cell count predicts the odds of kidney function decline in a Chinese community-based population.

BACKGROUND: Inflammatory processes are very important in the development of kidney disease. Nevertheless, the association between white blood cell (WBC) count and the risk of renal dysfunction has not been well-established, especially in subjects without chronic kidney disease (CKD). Our study investigated the association between WBC count and kidney function decline in a Chinese community-based population with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2. METHODS: A total of 3768 subjects who were enrolled in an atherosclerosis cohort in Beijing were included in this study. EGFRs were calculated at baseline and follow-up using the CKD-EPI formula. The outcomes of this study were renal function decline (RFD) (a drop in eGFR stage along with a decline in eGFR of 25% or exceeding 5 mL/min/1.73 m2/year), rapid eGFR decline (an annual decrease in eGFR exceeding 3 mL/min/1.73 m2), and incident CKD (eGFR <60 min/1.73 m2 at follow-up). Multivariate logistic regression models were used to evaluate the associations between WBC count and each outcome. RESULTS: On average, the subjects were 56.6 ± 8.5 years old, and 35.9% were male. Of the participants, 48.6% had hypertension and 17.4% had diabetes. The mean (SD) WBC count at baseline was 6.1 ± 1.5 × 109/L. The mean (SD) eGFR at baseline was 101.1 ± 10.6 mL/min/1.73 m2. After 2.3 years follow-up, the incidence rates of RFD, rapid eGFR decline and new CKD were 7.7, 20.9, and 0.8%, respectively. WBC count was significantly related to RFD, rapid eGFR decline and new CKD in the univariate analyses. Even after adjustment for demographic variables, comorbidities, medications and baseline eGFR, these associations remained. Moreover, similar trends in RFD were observed in nearly all subgroups stratified by each confounding variable. The increase in the odds of RFD associated with each 109/L increase in WBC count was significantly greater in subjects not undergoing treatment with lipid-lowering drugs than those not undergoing this treatment (P-interaction: 0.05). CONCLUSIONS: In conclusion, elevated WBC count served as a predictor of the odds of kidney function decline in this population, which supports the hypothesis that systemic inflammation may serve as a risk factor for CKD development.

Kidney Function and Fracture Risk: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: People with end-stage renal disease are at high risk for bone fracture. Less is known about fracture risk in milder chronic kidney disease and whether chronic kidney disease-associated fracture risk varies by sex or assessment with alternative kidney markers. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 10,955 participants from the Atherosclerosis Risk in Communities (ARIC) Study followed up from 1996 to 2011. PREDICTOR: Kidney function as assessed by creatinine-based estimated glomerular filtration rate (eGFRcr), urine albumin-creatinine ratio, and alternative filtration markers. OUTCOMES: Fracture-related hospitalizations determined by diagnostic code. MEASUREMENTS: Baseline kidney markers; hospitalizations identified by self-report during annual telephone contact and active surveillance of local hospital discharge lists. RESULTS: Mean age of participants was 63 years, 56% were women, and 22% were black. During a median follow-up of 13 years, there were 722 incident fracture-related hospitalizations. Older age, female sex, and white race were associated with higher risk for fracture (P<0.001). The relationship between eGFRcr and fracture risk was nonlinear: <60mL/min/1.73m(2), lower eGFRcr was associated with higher fracture risk (adjusted HR per 10mL/min/1.73m(2) lower, 1.24; 95% CI, 1.05-1.47); there was no statistically significant association for ≥60mL/min/1.73m(2) in the primary analysis. In contrast, there was a graded association between other markers of kidney function and subsequent fracture, including albumin-creatinine ratio (HR per doubling, 1.10; 95% CI, 1.06-1.14), cystatin C-based eGFR (HR per 1-SD decrease, 1.15; 95% CI, 1.06-1.25), and 1/ß2-microglobulin (HR per 1-SD decrease, 1.26, 95% CI, 1.15-1.37). LIMITATIONS: No bone mineral density assessment; one-time measurement of kidney function. CONCLUSIONS: Both low eGFR and higher albuminuria were significant risk factors for fracture in this community-based population. The shape of the association in the upper ranges of eGFR varied by the filtration marker used in estimation.

Estimated GFR and Subsequent Higher Left Ventricular Mass in Young and Middle-Aged Adults With Normal Kidney Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: Left ventricular hypertrophy is common and is associated with cardiovascular events and death among patients with known chronic kidney disease. However, the link between reduced glomerular filtration rate (GFR) and left ventricular mass index (LVMI) remains poorly explored among young and middle-aged adults with preserved kidney function. In this study, we examined the association of cystatin C-based estimated GFR (eGFRcys) and rapid decline in eGFR with subsequent LVMI. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: We included 2,410 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort with eGFRcys > 60mL/min/1.73m(2) at year 15 and who had an echocardiogram obtained at year 25. PREDICTOR: eGFRcys at year 15 and rapid decline in eGFRcys (defined as >3% per year over 5 years from years 15 to 20). OUTCOME: LVMI measured at year 25. MEASUREMENTS: We adjusted for age, sex, race, diabetes, body mass index, low- and high-density lipoprotein cholesterol levels, cumulative systolic blood pressure, and albuminuria. RESULTS: Mean age was 40±4 (SD) years, 58% were women, and 43% were black. After 10 years of follow-up, mean LVMI was 39.6±13.4g/m(2.7). Compared with eGFRcys > 90mL/min/1.73m(2) (n = 2,228), eGFRcys of 60 to 75mL/min/1.73m(2) (n = 29) was associated with 5.63 (95% CI, 0.90-10.36) g/m(2.7) greater LVMI (P = 0.02), but there was no association of eGFRcys of 76 to 90mL/min/1.73m(2) (n = 153) with LVMI after adjustment for confounders. Rapid decline in eGFRcys was associated with higher LVMI compared with participants without a rapid eGFRcys decline (ß coefficient, 1.48; 95% CI, 0.11-2.83; P = 0.03) after adjustment for confounders. LIMITATIONS: There were a limited number of participants with eGFRcys of 60 to 90mL/min/1.73m(2). CONCLUSIONS: Among young and middle-aged adults with preserved kidney function, eGFRcys of 60 to 75mL/min/1.73m(2) and rapid decline in eGFRcys were significantly associated with subsequently higher LVMI. Further studies are needed to understand the mechanisms that contribute to elevated LVMI in this range of eGFRcys.

Influence of renal function on mortality and ventricular arrhythmias in patients undergoing first implantable cardioverter-defibrillator generator replacement.

BACKGROUND: Impaired renal function is associated with increased mortality among patients with implantable cardioverter-defibrillators (ICDs). The relationship between renal function at time of ICD generator replacement and subsequent appropriate ICD therapies is not known. METHODS AND RESULTS: We identified 441 patients who underwent first ICD generator replacement between 2000 and 2011 and had serum creatinine measured within 30 days of their procedure. Patients were divided into tertiles based on estimated glomerular filtration rate (eGFR). Adjusted Cox proportional hazard and competing risk models were used to assess relationships between eGFR and subsequent mortality and appropriate ICD therapy. Median eGFR was 37.6, 59.3, and 84.8 mL/min/1.73 m(2) for tertiles 1-3, respectively. Five-year Kaplan-Meier survival probability was 34.8%, 61.4%, and 84.5% for tertiles 1-3, respectively (P < 0.001). After multivariable adjustment, compared to tertile 3, worse eGFR tertile was associated with increased mortality (HR 2.84, 95% CI [1.36-5.94] for tertile 2; HR 3.84, 95% CI [1.81-8.12] for tertile 1). At 5 years, 57.0%, 58.1%, and 60.2% of patients remained free of appropriate ICD therapy in tertiles 1-3, respectively (P = 0.82). After adjustment, eGFR tertile was not associated with future appropriate ICD therapy. Results were unchanged in an adjusted competing risk model accounting for death. CONCLUSIONS: At time of first ICD generator replacement, lower eGFR is associated with higher mortality, but not with appropriate ICD therapies. The poorer survival of ICD patients with reduced eGFR does not appear to be influenced by arrhythmia status, and there is no clear proarrhythmic effect of renal dysfunction, even after accounting for the competing risk of death.

The Urea-to-Creatinine Ratio Is Predictive of Worsening Kidney Function in Ambulatory Heart Failure Patients.

BACKGROUND: Changes in kidney function in heart failure patients convey important prognostic information. We investigated the association of the urea-to-creatinine (BUN/Cr) ratio, the fractional excretion of urea (FeUr), and the fractional excretion of sodium (FeNa) and subsequent declines in kidney function in ambulatory heart failure patients. METHODS AND RESULTS: We prospectively enrolled adult patients with ejection fraction <40% at a multidisciplinary heart failure clinic and measured serial measurements of laboratory values from September 2008 to July 2011. The study outcome was changes in the estimated glomerular filtration rate (eGFR). In 138 patients contributing 10,350 patient-hours of follow-up, we found that participants with a decline of >25% in eGFR had higher mean BUN/Cr ratio (0.110 ± 0.043 vs 0.086 ± 0.026; P = .02) and no difference in the FeNa (1.81 vs 1.43; P = .2) or FeUr (32.3 vs 37.2; P = .9) compared with those with no change. There was an association of BUN/Cr ratio with the rate of change of eGFR (coefficient -25.67, 95% confidence interval [CI] -10.99 to -40.35; P < .0001). The BUN/Cr ratio was an independent predictor of eGFR drop >25% (odds ratio 1.19, 95% CI 1.07-1.32) and improved model discrimination (c-statistic increased from 0.624 to 0.693) and reclassification (net reclassification index 11.38% [P < .0001], integrated discrimination improvement 5.24% [P = .02]). CONCLUSIONS: The BUN/Cr ratio is associated with worsening kidney function and adds incremental risk prediction information relative to traditional predictive measures in outpatients with heart failure at risk for worsening kidney disease.

Outcome in acute heart failure: prognostic value of acute kidney injury and worsening renal function.

BACKGROUND: The prognostic value of worsening renal function (WRF) in acute heart failure is debated. Moreover, it is not clear if the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in this context is detrimental. METHOD AND RESULTS: In a retrospective cohort study of 646 patients hospitalized for acute heart failure, the risk of death or readmission associated with acute kidney injury (AKI) present at admission, WRF during the 1st 7 days, and up-titration of ACEI/ARB were analyzed in a Cox proportional hazards model. AKI, WRF, hemoglobin concentration, ACEI/ARB up-titration, and use of loop diuretics before admission were significantly associated with the primary outcome in univariate analysis. In a multivariate model, the association remained significant for AKI (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.13-1.47; P = .0002), WRF (HR 1.24, 95% CI 1.06-1.45; P = .0059), and ACEI/ARB up-titration (HR 0.79, 95% CI 0.64-0.97; P = .026). There was no excess mortality in patients with ACEI/ARB up-titration despite WRF. CONCLUSIONS: Both AKI and WRF are strongly associated with poor outcome in patients hospitalized for acute heart failure. ACEI/ARB up-titration seems to be protective.

Chronic kidney disease in the Top End of the Northern Territory of Australia, 2002-2011: a retrospective cohort study using existing laboratory data.

BACKGROUND: The Northern Territory of Australia has a very high incidence of treated end-stage kidney disease (ESKD), largely confined to Indigenous Australians living in remote, under-resourced areas. Surveillance of chronic kidney disease (CKD) is still in its infancy in Australia. We estimate the prevalence and rate of progression of measured CKD across a region using inexpensive readily available laboratory information. METHODS: Using a retrospective de-identified extraction of all records with a serum creatinine or urinary albumin-to-creatinine ratio from the single largest ambulatory pathology provider to the Top End of the Northern Territory of Australia between 1st February 2002 and 31st December 2011, the yearly total and age-specific prevalence of measured microalbuminuria, overt albuminuria and estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2), and the prevalence of progressive CKD, were calculated. RESULTS: There was a steady increase in the proportion tested across all health districts in the region, more prominent in non-urban districts. In 2009, the regional adult prevalence of measured microalbuminuria and overt albuminuria was as high as 8.1 %, overt albuminuria alone up to 3.0 % and eGFR < 60 up to 2.3 %. Rates of progressive disease were extremely high, particularly for those with albuminuria (53.1-100 % for those with urinary albumin-creatinine ratio > 300 mg/mmol). CONCLUSIONS: The rates of testing, particularly in districts of high measured prevalence of markers of CKD, are encouraging. However, extremely high rates of progressive CKD are troubling. Further describing the outcomes of CKD in this population would require analysis of linked datasets.

The association of eGFR reporting with the timing of dialysis initiation.

Automated reporting of eGFR by laboratories has been widely implemented during the last decade. Over this same period, a steady increase in eGFR at dialysis initiation has been reported. This study examined trends in eGFR at dialysis initiation over time among incident dialysis patient populations before and after eGFR reporting. All patients who initiated dialysis between January of 2001 and December of 2010 in four Canadian provinces that implemented province-wide automated eGFR reporting and had an eGFR measure at dialysis initiation were included in the study (n=22,208). The primary outcome was change over time in eGFR among patients at dialysis initiation. An interrupted time series and adjusted multilevel regression models were used to determine the differences in eGFR at dialysis initiation before and after reporting. We observed a linear increase in the mean eGFR at dialysis initiation from 9.1 to 10.8 ml/min per m(2) during the study period. There was no change in the trajectory of the eGFR at dialysis initiation before or after eGFR reporting in crude or adjusted models accounting for case mix and facility characteristics. These findings were consistent among age and sex strata and when the proportions of patients with an eGFR≥10.5 or ≥12 ml/min per m(2) were examined. In conclusion, automated laboratory-based eGFR reporting did not influence eGFR at dialysis initiation among incident dialysis patient populations. Concerns that widespread eGFR reporting leads to earlier dialysis initiation are not supported by this study.

Persistent renal damage after contrast-induced acute kidney injury: incidence, evolution, risk factors, and prognosis.

BACKGROUND: The temporal evolution of renal function in patients with acute kidney injury after contrast medium (CI-AKI) is not well known. The aim of this observational study was to evaluate the incidence, risk factors, and prognostic implications of persistent renal damage (RD) in patients with preexistent moderate-to-severe renal dysfunction. METHODS AND RESULTS: From June 2003 to March 2008, 3986 patients underwent coronary angiography at our institution; 1490 of 3986 had an estimated creatinine clearance of <60 mL/min and were enrolled. CI-AKI was defined as an absolute increase ≥ 0.5 mg/dL over baseline serum creatinine within 3 days after the administration of contrast medium (iodixanol). In patients who developed CI-AKI, persistent RD was defined as a relative decrease of creatinine clearance ≥ 25% over baseline at 3 months. Patients whose creatinine clearance returned to baseline (or nearly) were classified as transient RD. The overall incidence of CI-AKI was 12.1%, and persistent RD occurred in 18.6% of CI-AKI patients. At Cox regression analysis, nephropathy risk score ≥ 17, left ventricular ejection fraction ≤ 30%, and increased value of serum creatinine ≥ 1.5-fold from baseline within 5 days were found to be significant risk factors for persistent RD. At 5 years, the incidence of death was significantly higher in patients with persistent RD than in both patients with transient RD (P=0.015) and those without CI-AKI (P=0.0001). A similar trend was observed for the combined end point of death, dialysis and cardiovascular events. CONCLUSIONS: These results suggest that CI-AKI is not always a transient, benign creatininopathy, but rather a direct cause of worsening renal function. The occurrence of CI-AKI can identify patients at increased risk of cardiovascular events.

Update on cystatin C: incorporation into clinical practice.

Kidney function monitoring using creatinine-based glomerular filtration rate estimation is a routine part of clinical practice. Emerging evidence has shown that cystatin C may improve classification of glomerular filtration rate for defining chronic kidney disease in certain clinical populations and assist in understanding the complications of chronic kidney disease. In this review and update, we summarize the overall literature on cystatin C, critically evaluate recent high-impact studies, highlight the role of cystatin C in recent kidney disease guidelines, and suggest a practical approach for clinicians to incorporate cystatin C into practice. We conclude by addressing frequently asked questions related to implementing cystatin C use in a clinical setting.

Tubular secretion of creatinine in autosomal dominant polycystic kidney disease: consequences for cross-sectional and longitudinal performance of kidney function estimating equations.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by renal tubular cell proliferation and dedifferentiation, which may influence tubular secretion of creatinine (CCr[TS]). STUDY DESIGN: Diagnostic test study. SETTING & PARTICIPANTS: We therefore investigated CCr(TS) in patients with ADPKD and controls and studied consequences for the performance of glomerular filtration rate (GFR) estimating equations. INDEX & REFERENCE TESTS: In patients with ADPKD and healthy controls, we measured GFR as (125)I-iothalamate clearance while simultaneously determining creatinine clearance. OTHER MEASUREMENTS: 24-hour urinary albumin excretion. RESULTS: In 121 patients with ADPKD (56% men; mean age, 40 ± 11 [SD] years) and 215 controls (48% men; mean age, 53 ± 10 years), measured GFR (mGFR) was 78 ± 30 and 98 ± 17 mL/min/1.73 m(2), respectively, and CCr(TS) was 15.9 ± 10.8 and 10.9 ± 10.6 mL/min/1.73 m(2), respectively (P < 0.001). The higher CCr(TS) in patients with ADPKD remained significant after adjustment for covariates and appeared to be dependent on mGFR. Correlation and accuracy between mGFR and CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) estimated GFR (eGFR) were 0.95 and 99%, respectively; between mGFR and MDRD (Modification of Diet in Renal Disease) Study eGFR, they were 0.93 and 97%, respectively. Values for bias, precision, and accuracy were similar or slightly better than in controls. In addition, change in mGFR during 3 years of follow-up in 45 patients with ADPKD correlated well with change in eGFR. LIMITATIONS: Cross-sectional, single center. CONCLUSIONS: CCr(TS) in patients with ADPKD is higher than that in controls, but this effect is limited and observed at only high-normal mGFR. Consequently, the CKD-EPI and MDRD Study equations perform relatively well in estimating GFR and change in GFR in patients with ADPKD.

Biochemical evidence of mild hepatic dysfunction identifies decompensated heart failure patients with reversible renal dysfunction.

BACKGROUND: Differentiation of HF-induced renal dysfunction (RD) from irreversible intrinsic kidney disease is challenging, likely related to the multifactorial pathophysiology underlying HF-induced RD. In contrast, HF-induced liver dysfunction results in characteristic laboratory abnormalities. Given that similar pathophysiologic factors are thought to underlie both conditions, and that the liver and kidneys share a common circulatory environment, patients with laboratory evidence of HF-induced liver dysfunction may also have a high incidence of potentially reversible HF-induced RD. METHODS AND RESULTS: Hospitalized patients with a discharge diagnosis of HF were reviewed (n = 823). Improvement in renal function (IRF) was defined as a 20% improvement in estimated glomerular filtration rate (eGFR). An elevated international normalized ratio (INR; odds ratio [OR] 2.8; P < .001), bilirubin (BIL; OR 2.2; P < .001), aspartate aminotransferase (AST; OR 1.8; P = .004), and alanine aminotransferase (ALT; OR 2.1; P = .001) were all significantly associated with IRF. Among patients with baseline RD (eGFR ≤45 mL min(-1) 1.73 m(-2)), associations between liver dysfunction and IRF were particularly strong (INR: OR 5.7 [P < .001]; BIL: OR 5.1 [P < .001]; AST: OR 2.9 [P = .005]; ALT: OR 4.8 [P < .001]). CONCLUSIONS: Biochemical evidence of mild liver dysfunction is associated with reversible RD in decompensated HF patients. In the absence of methodology to directly identify HF-induced RD, signs of HF-induced dysfunction of other organs may serve as an accessible method by which HF-induced RD is recognized.

Factors influencing the decision to start renal replacement therapy: results of a survey among European nephrologists.

BACKGROUND: Little is known about the criteria nephrologists use in the decision of when to start renal replacement therapy (RRT) in early referred adult patients. We evaluated opinions of European nephrologists on the decision for when to start RRT. STUDY DESIGN: European web-based survey. PREDICTORS: Patient presentations described as uncomplicated patients, patients with unfavorable clinical and unfavorable social conditions, or patients with specific clinical, social, and logistical factors. SETTING & PARTICIPANTS: Nephrologists from 11 European countries. OUTCOMES & MEASUREMENTS: We studied opinions of European nephrologists about the influence of clinical, social, and logistical factors on decision making regarding when to start RRT, reflecting practices in place in 2009. Questions included target levels of kidney function at the start of RRT and factors accelerating or postponing RRT initiation. Using linear regression, we studied determinants of target estimated glomerular filtration rate (eGFR) at the start of RRT. RESULTS: We received 433 completed surveys. The median target eGFR selected to start RRT in uncomplicated patients was 10.0 (25th-75th percentile, 8.0-10.0) mL/min/1.73 m(2). Level of excretory kidney function was considered the most important factor in decision making regarding uncomplicated patients (selected by 54% of respondents); in patients with unfavorable clinical versus social conditions, this factor was selected by 24% versus 32%, respectively. Acute clinical factors such as life-threatening hyperkalemia refractory to medical therapy (100%) and uremic pericarditis (98%) elicited a preference for an immediate start, whereas patient preference (69%) and vascular dementia (66%) postponed the start. Higher target eGFRs were reported by respondents from high- versus low-RRT-incidence countries (10.4 [95% CI, 9.9-10.9] vs 9.1 mL/min/1.73 m(2)) and from for-profit versus not-for-profit centers (10.1 [95% CI, 9.5-10.7] vs 9.5 mL/min/1.73 m(2)). LIMITATIONS: We were unable to calculate the exact response rate and examined opinions rather than practice for 433 nephrologists. CONCLUSIONS: Only for uncomplicated patients did half the nephrologists consider excretory kidney function as the most important factor. Future studies should assess the weight of each factor affecting decision making.