Age-specific associations of reduced estimated glomerular filtration rate with concurrent chronic kidney disease complications

Summary

Background and objectives

It has been suggested that moderate reductions in estimated GFR (eGFR) among older adults may not reflect chronic kidney disease (CKD).

Design, setting, participants, & measurements

We examined age-specific (<60, 60 to 69, 70 to 79, and ≥80 years) associations between eGFR level and six concurrent CKD complications among 30,528 participants from the National Health and Nutrition Examination Survey (NHANES) 1988 to 1994 and 1999 to 2006 (n = 8242 from NHANES 2003 to 2006 for hyperparathyroidism). Complications included anemia (hemoglobin <12 g/dl women, <13.5 g/dl men), acidosis (bicarbonate <22 mEq/L), hyperphosphatemia (phosphorus ≥4.5 mg/dl), hypoalbuminemia (albumin <3.5 mg/dl), hyperparathyroidism (intact parathyroid hormone ≥70 pg/ml), and hypertension (systolic/diastolic BP ≥140/90 mmHg or antihypertensive use).

Results

Among participants ≥80 years old, compared with those with estimated GFR (eGFR) ≥60 ml/min per 1.73 m², the multivariable adjusted prevalence ratios (95% confidence interval) associated with eGFR levels of 45 to 59 and <45 ml/min per 1.73 m² were 1.39 (1.11 to1.73) and 2.06 (1.59 to 2.67) for anemia, 1.33 (0.89 to 1.98) and 2.47 (1.52 to 4.00) for acidosis, 1.11 (0.70 to 1.76) and 2.16 (1.36 to 3.42) for hyperphosphatemia, 2.04 (1.39 to 3.00) and 2.83 (1.76 to 4.53) for hyperparathyroidism and 1.09 (1.03 to 1.14), and 1.12 (1.05 to 1.19) for hypertension, respectively. Higher prevalence ratios for these complications at lower eGFR levels were also present at younger ages. Reduced eGFR was associated with hypoalbuminemia only for adults <70.

Conclusions

Reduced eGFR was associated with a higher prevalence of several concurrent CKD complications, regardless of age.     

Glomerular hyperfiltration and renal progression in children with autosomal dominant polycystic kidney disease

Summary

Background and objectives

The purpose of this study was to determine whether glomerular hyperfiltration (GH) occurring early in autosomal dominant polycystic kidney disease (ADPKD) is indicative of more rapid disease progression in children.

Design, setting, participants, & measurements

One hundred eighty children with ADPKD (ages 4 to 18 years) with normal renal function were examined by renal ultrasound. Renal volume was calculated using a standard formula for a modified ellipsoid. Creatinine clearance was calculated from serum creatinine and 24-hour urine creatinine. GH was defined as creatinine clearance ≥140 ml/min per 1.73 m².

Results

Thirty-two children had GH (mean age 11.4 ± 3.6 years) and 148 had normal renal function (mean age 10.8 ± 3.9 years). Patients with GH at baseline demonstrated an increased rate of total renal volume growth (β: rate of change = +19.3 ± 10.8 cm³/year) over 5 years compared with those without GH at baseline (β = −4.3 ± 7.7 cm³/year), P = 0.008. Those with GH at baseline experienced a faster decline in creatinine clearance in subsequent years (β = −5.0 ± 0.8 ml/min per 1.73 m² per year) compared with those without GH at baseline (β = +1.0 ± 0.4 ml/min per 1.73 m² per year), P < 0.0001.

Conclusions

This study revealed that occurrence of GH in ADPKD children is associated with a significantly faster decline in renal function and higher rate of kidney enlargement over time. GH combined with the increased renal volume may therefore be used as an early marker for a more severe progression of ADPKD in children.     

Urinary Potassium Excretion and Renal and Cardiovascular Complications in Patients with Type 2 Diabetes and Normal Renal Function

Background and objectives

We investigated the association of urinary potassium and sodium excretion with the incidence of renal failure and cardiovascular disease in patients with type 2 diabetes.

Design, setting, participants, & measurements

A total of 623 Japanese type 2 diabetic patients with eGFR≥60 ml/min per 1.73 m² were enrolled in this observational follow-up study between 1996 and 2003 and followed-up until 2013. At baseline, a 24-hour urine sample was collected to estimate urinary potassium and sodium excretion. The primary end point was renal and cardiovascular events (RRT, myocardial infarction, angina pectoris, stroke, and peripheral vascular disease). The secondary renal end points were the incidence of a 50% decline in eGFR, progression to CKD stage 4 (eGFR<30 ml/min per 1.73 m²), and the annual decline rate in eGFR.

Results

During the 11-year median follow-up period, 134 primary end points occurred. Higher urinary potassium excretion was associated with lower risk of the primary end point, whereas urinary sodium excretion was not. The adjusted hazard ratios for the primary end point in Cox proportional hazards analysis were 0.56 (95% confidence interval [95% CI], 0.33 to 0.95) in the third quartile of urinary potassium excretion (2.33–2.90 g/d) and 0.33 (95% CI, 0.18 to 0.62) in the fourth quartile (>2.90 g/d) compared with the lowest quartile (<1.72 g/d). Similar associations were observed for the secondary renal end points. The annual decline rate in eGFR in the fourth quartile of urinary potassium excretion (–1.3 ml/min per 1.73 m²/y; 95% CI, –1.5 to –1.0) was significantly slower than those in the first quartile (–2.2; 95% CI, –2.4 to –1.8).

Conclusions

Higher urinary potassium excretion was associated with the slower decline of renal function and the lower incidence of cardiovascular complications in type 2 diabetic patients with normal renal function. Interventional trials are necessary to determine whether increasing dietary potassium is beneficial.     

Relationship between blood pressure and incident chronic kidney disease in hypertensive patients

Summary

Background and objectives

Hypertension is an important cause of chronic kidney disease (CKD). Identifying risk factors for progression to CKD in patients with normal kidney function and hypertension may help target therapies to slow or prevent decline of kidney function. Our objective was to identify risk factors for development of incident CKD and decline in estimated GFR (eGFR) in hypertensive patients.

Design, setting, participants, & measurements

Cox proportional hazards models were used to assess the relationship between incident CKD (defined as eGFR <60 ml/min per 1.73 m²) and potential risk factors for CKD from a registry of hypertensive patients.

Results

Of 43,305 patients meeting the inclusion criteria, 12.1% (5236 patients) developed incident CKD. Diabetes was the strongest predictor of incident CKD (hazard ratio, 1.96; 95% confidence interval, 1.84 to 2.09) and was associated with the greatest rate of decline in eGFR (−2.2 ml/min per 1.73 m² per year). Time-varying systolic BP was associated with incident CKD with risk increasing above 120 mmHg; each 10-mmHg increase in baseline and time-varying systolic BP was associated with a 6% increase in the risk of developing CKD (hazard ratio, 1.06; 95% confidence interval, 1.04 to 1.08 for both). Time-weighted systolic BP was associated with a more rapid decline in eGFR of an additional 0.2 ml/min per 1.73 m² per year decline for every 10-mmHg increase in systolic BP.

Conclusions

We found that time-varying systolic BP was associated with incident CKD, with an increase in risk above a systolic BP of 120 mmHg among individuals with hypertension.     

Low-molecular-weight proteins as prognostic markers in idiopathic membranous nephropathy

Summary

Background

Accurate prediction of prognosis in idiopathic membranous nephropathy (iMN) allows restriction of immunosuppressive therapy to patients at high risk for ESRD. Here we re-evaluate urinary low-molecular-weight proteins as prognostic markers and explore causes of misclassification.

Design, setting, participants, & measurements

In a cohort of 129 patients with serum creatinine concentration <135 μmol/L and proteinuria ≥3.0 g/10 mmol, urinary α1- (uα1m) and β2-microglobulin (uβ2m) excretion rate was determined. Urinary α1m and uβ2m-creatinine ratio was also obtained. We defined progression as a rise in serum creatinine ≥50% or ≥25% and an absolute level ≥135 μmol/L.

Results

Median survival time was 25 months, and 47% of patients showed progression. The area under the receiver operating characteristic curve for uβ2m was 0.81 (95% CI: 0.73 to 0.89). Using a threshold value of 1.0 μg/min, sensitivity and specificity were 73% and 75%, respectively. Similar accuracy was observed for the uβ2m-creatinine ratio with sensitivity and specificity of 75% and 73%, respectively, at a threshold of 1.0 μg/10 mmol creatinine. Similar accuracy was found for uα1m and uα1m-creatinine ratio. Blood Pressure and cholesterol contributed to misclassification. Repeated measurements improved accuracy in patients with persistent proteinuria: the positive predictive value of uβ2m increased from 72% to 89% and the negative predictive value from 76% to 100%.

Conclusions

Urinary excretion of uα2m and uβ2m predict prognosis in iMN. A spot urine sample can be used instead of a timed sample. A repeated measurement after 6 to 12 months increases prognostic accuracy.     

Age-Specific Association of Reduced Estimated Glomerular Filtration Rate and Albuminuria with All-Cause Mortality

Summary

Background and objectives

It has been suggested that reduced estimated GFR (eGFR) among older adults does not necessarily reflect a pathologic phenomenon.

Design, setting, participants, & measurements

We examined the association between eGFR and albumin-to-creatinine ratio (ACR) and all-cause mortality stratified by age (45 to 59.9, 60 to 69.9, 70 to 79.9, and ≥80 years) among 24,350 U.S. adults in the population-based REasons for Geographic and Racial Differences in Stroke (REGARDS) study. A spot urine sample was used to calculate ACR, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to calculate eGFR. All-cause mortality was assessed over a median follow-up of 4.5 years.

Results

Among participants ≥80 years of age (n = 1669), the age, race, gender, and geographic region of residence adjusted hazard ratios (95% confidence intervals) for mortality associated with eGFR levels of 45 to 59.9 and <45 ml/min per 1.73 m², versus ≥60 ml/min per 1.73 m², were 1.6 (1.3 – 2.1) and 2.2 (1.7 – 2.9), respectively. Also, among participants ≥80 years of age, the hazard ratios for mortality associated with ACR levels of 10 to 29.9, 30 to 299.9, and ≥300 mg/g, versus <10 mg/g, were 1.7 (1.3 – 2.1), 2.5 (1.9 – 3.3), and 5.1 (3.6 – 7.4), respectively. These associations were present after further multivariable adjustment and within the younger age groupings studied.

Conclusions

These data suggest that reduced eGFR and albuminuria confer an increased risk for mortality in all age groups, including adults ≥80 years of age.     

A Nurse-coordinated Model of Care versus Usual Care for Stage 3/4 Chronic Kidney Disease in the Community: A Randomized Controlled Trial

Summary

Background and objectives

It is unclear how to optimally care for chronic kidney disease (CKD). This study compares a new coordinated model to usual care for CKD.

Design, setting, participants, & measurements

A randomized trial in nephrology clinics and the community included 474 patients with median estimated GFR (eGFR) 42 ml/min per 1.73 m² identified by laboratory-based case finding compared care coordinated by a general practitioner (controls) with care by a nurse-coordinated team including a nephrologist (intervention) for a median (interquartile range [IQR]) of 742 days. 32% were diabetic, 60% had cardiovascular disease, and proteinuria was minimal. Guided by protocols, the intervention team targeted risk factors for adverse kidney and cardiovascular outcomes. Serial eGFR and clinical events were tracked.

Results

The average decline in eGFR over 20 months was −1.9 ml/min per 1.73 m². eGFR declined by ≥4 ml/min per 1.73 m² within 20 months in 28 (17%) intervention patients versus 23 (13.9%) control patients. Control of BP, LDL, and diabetes were comparable across groups. In the intervention group there was a trend to greater use of renin-angiotensin blockers and more use of statins in those with initial LDL >2.5 mmol/L. Treatment was rarely required for anemia, acidosis, or disordered mineral metabolism. Clinical events occurred in 5.2% per year.

Conclusions

Patients with stage 3/4 CKD identified through community laboratories largely had nonprogressive kidney disease but had cardiovascular risk. Over a median of 24 months, the nurse-coordinated team did not affect rate of GFR decline or control of most risk factors compared with usual care.     

Aliskiren in Combination with Losartan Reduces Albuminuria Independent of Baseline Blood Pressure in Patients with Type 2 Diabetes and Nephropathy

Summary

Background and objectives

Elevated BP contributes to development and progression of proteinuria and decline in renal function in patients with type 2 diabetes. Our post hoc analysis assessed the baseline BP influence on the antiproteinuric effect in the Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) study.

Design, setting, participants, & measurements

In the AVOID study, 599 hypertensive type 2 diabetic patients with nephropathy received 6 months of aliskiren (150 mg force titrated to 300 mg daily after 3 months) or placebo added to losartan (100 mg) daily and optimal antihypertensive therapy. Changes in early morning urinary albumin:creatinine ratio and eGFR at week 24 were assessed by subgroups of baseline BP: Group A (prespecified target), <130/80 mmHg (n = 159); Group B, <140/90 mmHg but ≥130/80 mmHg (n = 189); and Group C (insufficient BP control), ≥140/90 mmHg (n = 251).

Results

Mean baseline BP (mmHg) levels for Groups A, B, and C were 120/71, 133/78, and 145/81, respectively. BP during the trial was nearly identical to baseline levels in all groups. The antiproteinuric effects of aliskiren were consistent across subgroups of baseline BP (19 to 22% reduction versus placebo). In Group C, the decline in eGFR was significantly lower with aliskiren than with placebo (P = 0.013).

Conclusions

Aliskiren (300 mg) added to losartan (100 mg) plus optimal antihypertensive therapy provides antiproteinuric effects independent of BP in patients with type 2 diabetes and nephropathy. Renal function was better preserved with aliskiren in patients with insufficient BP control.     

Tolvaptan in autosomal dominant polycystic kidney disease: three years' experience

Summary

Background and objectives

Autosomal dominant polycystic kidney disease (ADPKD), a frequent cause of end-stage renal disease, has no cure. V2-specific vasopressin receptor antagonists delay disease progression in animal models.

Design, setting, participants, and measurements

This is a prospectively designed analysis of annual total kidney volume (TKV) and thrice annual estimated GFR (eGFR) measurements, from two 3-year studies of tolvaptan in 63 ADPKD subjects randomly matched 1:2 to historical controls by gender, hypertension, age, and baseline TKV or eGFR. Prespecified end points were group differences in log-TKV (primary) and eGFR (secondary) slopes for month 36 completers, using linear mixed model (LMM) analysis. Sensitivity analyses of primary and secondary end points included LMM using all subject data and mixed model repeated measures (MMRM) of change from baseline at each year. Pearson correlation tested the association between log-TKV and eGFR changes.

Results

Fifty-one subjects (81%) completed 3 years of tolvaptan therapy; all experienced adverse events (AEs), with AEs accounting for six of 12 withdrawals. Baseline TKV (controls 1422, tolvaptan 1635 ml) and eGFR (both 62 ml/min per 1.73 m²) were similar. Control TKV increased 5.8% versus 1.7%/yr for tolvaptan (P < 0.001, estimated ratio of geometric mean 0.96 [95% confidence interval 0.95 to 0.97]). Corresponding annualized eGFR declined: −2.1 versus −0.71 ml/min per 1.73 m²/yr (P = 0.01, LMM group difference 1.1 ml/min per 1.73 m²/yr [95% confidence interval 0.24 to 1.9]). Sensitivity analyses including withdrawn subjects were similar, whereas MMRM analyses were significant at each year for TKV and nonsignificant for eGFR. Increasing TKV correlated with decreasing eGFR (r = −0.21, P < 0.01).

Conclusion

ADPKD cyst growth progresses more slowly with tolvaptan than in historical controls, but AEs are common.     

Factors Associated with Non-Compliance During 16-Hour Long Call Shifts

Background

Duty hour restrictions limit shift length to 16 hours during the 1^st post-graduate year. Although many programs utilize a 16-hour “long call” admitting shift on inpatient services, compliance with the 16-hour shift length and factors responsible for extended shifts have not been well examined.

Objective

To identify the incidence of and operational factors associated with extended long call shifts and residents’ perceptions of the safety and educational value of the 16-hour long call shift in a large internal medicine residency program.

Design, Participants, and Main Measures

Between August and December of 2010, residents were sent an electronic survey immediately following 16-hour long call shifts, assessing departure time and shift characteristics. We used logistic regression to identify independent predictors of extended shifts. In mid-December, all residents received a second survey to assess perceptions of the long call admitting model.

Key Results

Two-hundred and thirty surveys were completed (95 %). Overall, 92 of 230 (40 %) shifts included ≥1 team member exceeding the 16-hour limit. Factors independently associated with extended shifts per 3-member team were 3–4 patients (adjusted OR 5.2, 95 % CI 1.9–14.3) and > 4 patients (OR 10.6, 95 % CI 3.3–34.6) admitted within 6 hours of scheduled departure and > 6 total admissions (adjusted OR 2.9, 95 % CI 1.05–8.3). Seventy-nine of 96 (82 %) residents completed the perceptions survey. Residents believed, on average, teams could admit 4.5 patients after 5 pm and 7 patients during long call shifts to ensure compliance. Regarding the long call shift, 73 % agreed it allows for safe patient care, 60 % disagreed/were neutral about working too many hours, and 53 % rated the educational value in the top 33 % of a 9-point scale.

Conclusions

Compliance with the 16-hour long call shift is sensitive to total workload and workload timing factors. Knowledge of such factors should guide systems redesign aimed at achieving compliance while ensuring patient care and educational opportunities.KEY WORDS: medical education-graduate, medical education, systems-based practice, duty hours     

The Association between a Mediterranean-Style Diet and Kidney Function in the Northern Manhattan Study Cohort

Background and objectives

Various dietary strategies have been investigated to slow kidney function decline. However, it is unknown whether a Mediterranean diet, which has been associated with improved cardiovascular risk, is associated with change in kidney function.

Design, setting, participants, & measurements

This study used the Northern Manhattan Study, a prospective, multiethnic, observational cohort of participants who were stroke free at baseline. Data were collected between 1993 and 2008. Serum creatinine measurements were taken a mean 6.9 years apart. A baseline dietary questionnaire was extrapolated into a previously used 9-point scoring system (MeDi). The primary outcome was incident eGFR<60 ml/min per 1.73 m²using the Modification of Diet in Renal Disease formula. A secondary outcome was the upper quartile of annualized eGFR decline (≥2.5 ml/min per 1.73 m² per year). Conditional logistic regression models adjusted for demographics and baseline vascular risk factors.

Results

Mean baseline age was 64 years, with 59% women and 65% Hispanics (N=900); mean baseline eGFR was 83.1 ml/min per 1.73 m². Incident eGFR<60 ml/min per 1.73 m² developed in 14% . In adjusted models, every 1-point increase in the MeDi score, indicating increasing adherence to a Mediterranean diet, was associated with decreased odds of incident eGFR<60 ml/min per 1.73 m² (odds ratio, 0.83; 95% confidence interval, 0.71 to 0.96) and decreased odds of being in the upper quartile of eGFR decline (odds ratio, 0.88; 95% confidence interval, 0.79 to 0.98).

Conclusions

A Mediterranean diet was associated with a reduced incidence of eGFR<60 ml/min per 1.73 m² and upper quartile of eGFR decline in a multiethnic cohort.     

Echocardiographic parameters are independently associated with rate of renal function decline and progression to dialysis in patients with chronic kidney disease

Summary

Background and objectives

Cardiac abnormalities were frequently noted in patients with chronic kidney disease (CKD). This study is designed to assess whether echocardiographic parameters are associated with rate of renal function decline and progression to dialysis in CKD stage 3 to 5 patients.

Design, setting, participants, & measurements

This longitudinal study enrolled 415 patients. The renal end point was defined as commencement of dialysis. The change in renal function was measured by estimated GFR (eGFR) slope.

Results

Progression to dialysis was predicted by wide pulse pressure, low albumin, low hemoglobin, high calcium-phosphorous product, proteinuria, diuretics use, and concentric left ventricular hypertrophy (LVH) (hazard ratio, 2.03; 95% confidence interval [CI], 1.00 to 4.10; P = 0.05). The eGFR slope was negatively associated with total cholesterol, uric acid, proteinuria, diuretics use, and left atrial (LA) diameter (change in slope, −0.50; 95% CI, −0.89 to −0.11; P = 0.01) and positively associated with albumin and left ventricular ejection fraction (LVEF) (change in slope, 0.06; 95% CI, 0.03 to 0.08; P < 0.001).

Conclusions

Our study in patients of CKD stage 3 to 5 demonstrated that concentric LVH was associated with progression to dialysis, and that increased LA diameter and decreased LVEF were associated with faster renal function decline. Echocardiography may help identify high-risk groups with progressive decline in renal function to dialysis and rapid progression of renal dysfunction in CKD stage 3 to 5 patients.     

Associations among Estimated Glomerular Filtration Rate,Proteinuria, and Adverse Cardiovascular Outcomes

Summary

Background and objectives

Most studies of chronic kidney disease (CKD) and outcomes focus on mortality and ESRD, with limited data on other adverse outcomes. This study examined the associations among proteinuria, eGFR, and adverse cardiovascular (CV) events.

Design, setting, participants, & measurements

This was a population-based longitudinal study with patients identified from province-wide laboratory data from Alberta, Canada, between 2002 and 2007. Selected for this study from a total of 1,526,437 patients were 920,985 (60.3%) patients with at least one urine dipstick measurement and 102,701 patients (6.7%) with at least one albumin-creatinine ratio (ACR) measurement. Time to hospitalization was considered for one of four indications: congestive heart failure (CHF), coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI), peripheral vascular disease (PVD), and stroke/transient ischemic attacks [TIAs] (cerebrovascular accident [CVA]/TIA).

Results

After a median follow-up of 35 months, in fully adjusted models and compared with patients with estimated GFR (eGFR) of 45 to 59 ml/min per 1.73 m² and no proteinuria, patients with heavy proteinuria by dipstick and eGFR ≥ 60 ml/min per 1.73 m² had higher rates of CABG/PCI and CVA/TIA. Similar results were obtained in patients with proteinuria measured by ACR.

Conclusions

Risks of major CV events at a given level of eGFR increased with higher levels of proteinuria. The findings extend current data on risk of mortality and ESRD. Measurement of proteinuria is of incremental prognostic benefit at every level of eGFR. The data support use of proteinuria measurement with eGFR for definition and risk stratification in CKD.     

Sperm quality before treatment in patients with early stage Hodgkin’s lymphoma enrolled in EORTC-GELA Lymphoma Group trials

Background

Although widely recommended, cryopreservation of sperm is sometimes not performed for patients with Hodgkin’s lymphoma because of presumed poor sperm quality related to the disease. We investigated sperm quality and factors determining it in untreated patients with early stage Hodgkin’s lymphoma.

Design and Methods

Of 2362 males who participated in EORTC H6–H9 trials, 474 (20%) had data available. Sperm quality was defined according to World Health Organization guidelines. Determining factors were studied by logistic regression analysis.

Results

The median sperm concentration was 40×10⁶/mL (range, 0–345×10⁶/mL) and the median motility 50% (range, 0–90%). Sperm quality was good (concentration ≥20×10⁶/mL and motility ≥50%), intermediate (concentration ≥5×10⁶/mL) and poor (concentration <5×10⁶/mL but >0) in 41%, 49% and 7% of patients, respectively. Three percent of the patients were azoospermic. No relation was found between sperm quality and age or clinical stage of the Hodgkin’s lymphoma, but B-symptoms and elevated erythrocyte sedimentation rate predicted poor sperm quality. The odds ratios for the association of poor sperm quality with the variables examined were: presence of B-symptoms, 2.77 (95% CI, 1.50–5.12; p=0.001); erythrocyte sedimentation rate of 50 mm/h or greater, 2.35 (95% CI, 1.24–4.43; p=0.009); fever, 3.22 (95% CI, 1.41–7.33; p=0.005), and night sweats, 3.78 (95% CI, 1.97–7.26; p<0.001). There was no relation between sperm quality and pre-treatment follicle stimulating hormone level.

Conclusions

In this large study of males with Hodgkin’s lymphoma, 90% had good or intermediate sperm quality. Three percent were azoospermic. There was an association between sperm quality and the presence or absence of B-symptoms, in particular fever and night sweats. With modern fertilization techniques, in most patients with early-stage Hodgkin’s lymphoma sperm quality before treatment is good enough for future fatherhood.     

Rate of Change in Renal Function and Mortality in Elderly Treated Hypertensive Patients

Background and objectives

Evidence relating the rate of change in renal function, measured as eGFR, after antihypertensive treatment in elderly patients to clinical outcome is sparse. This study characterized the rate of change in eGFR after commencement of antihypertensive treatment in an elderly population, the factors associated with eGFR rate change, and the rate’s association with all-cause and cardiovascular mortality.

Design, setting, participants, & measurements

Data from the Second Australian National Blood Pressure study were used, where 6083 hypertensive participants aged ≥65 years were enrolled during 1995–1997 and followed for a median of 4.1 years (in-trial). Following the Second Australian National Blood Pressure study, participants were followed-up for a further median 6.9 years (post-trial). The annual rate of change in the eGFR was calculated in 4940 participants using creatinine measurements during the in-trial period and classified into quintiles (Q) on the basis of the following eGFR changes: rapid decline (Q1), decline (Q2), stable (Q3), increase (Q4), and rapid increase (Q5).

Results

A rapid decline in eGFR in comparison with those with stable eGFRs during the in-trial period was associated with older age, living in a rural area, wider pulse pressure at baseline, receiving diuretic-based therapy, taking multiple antihypertensive drugs, and having blood pressure <140/90 mmHg during the study. However, a rapid increase in eGFR was observed in younger women and those with a higher cholesterol level. After adjustment for baseline and in-trial covariates, Cox-proportional hazard models showed a significantly greater risk for both all-cause (hazard ratio, 1.28; 95% confidence interval, 1.09 to 1.52; P=0.003) and cardiovascular (hazard ratio, 1.40; 95% confidence interval, 1.11 to 1.76; P=0.004) mortality in the rapid decline group compared with the stable group over a median of 7.2 years after the last eGFR measure. No significant association with mortality was observed for a rapid increase in eGFR.

Conclusions

In elderly persons with treated hypertension, a rapid decline in eGFR is associated with a higher risk of mortality.     

Long-Term Treatment Efficacy and Safety of Clevudine Therapy in Na?ve Patients with Chronic Hepatitis B

Background/Aims

Clevudine (CLV) has potent antiviral activity against chronic hepatitis B (CHB) virus infection. The long-term efficacy and safety of CLV therapy in naïve patients with CHB were investigated.

Methods

In this retrospective study, 152 naïve Korean patients with CHB who received 30 mg of CLV once daily for at least 12 months were investigated.

Results

The cumulative rates at months 12, 24, and 36, respectively, were 65.8%, 74.7%, and 74.7% for undetectable serum hepatitis B virus (HBV) DNA (<12 IU/mL); 77.6%, 86.2%, and 86.2% for normalization of serum alanine aminotransferase (<40 IU/L); 17.6%, 23.5%, and 23.5% for hepatitis B e antigen (HBeAg) loss or seroconversion; and 6.6%, 22.5%, and 30.0% for viral breakthrough. HBeAg positivity (p=0.010), baseline serum HBV DNA level ≥6 log₁₀ IU/mL (p=0.032) and detectable serum HBV DNA (≥12 IU/mL) at week 24 (p=0.023) were independently associated with the development of viral breakthrough. During follow-up, CLV-induced myopathy developed in 5.9% of patients.

Conclusions

The results of long-term CLV therapy for the treatment of naïve patients with CHB showed a high frequency of antiviral resistance and substantial associated myopathy. Therefore, we advise that CLV should not be used as a first-line treatment for naïve patients given the availability of other more potent, safer antiviral agents.     

Hospital-acquired Acute Kidney Injury: An Analysis of Nadir-to-Peak Serum Creatinine Increments Stratified by Baseline Estimated GFR

Summary

Background and objectives

Serum creatinine (sCr) increments currently used to define acute kidney injury (AKI) do not take into consideration the baseline level of kidney function. The objective of this study was to establish whether baseline estimated GFR (eGFR) provides additional risk stratification to sCr-based increments for defining AKI.

Design, setting, participants, & measurements

29,645 adults hospitalized at an acute care facility were analyzed. Hospital-acquired AKI was defined by calculating the difference between the nadir and subsequent peak sCr.

Results

Different thresholds of nadir-to-peak sCr were found to be independently associated with increased in-hospital mortality according to baseline eGFR strata. A nadir-to-peak sCr minimum threshold of ≥0.2, ≥0.3, and ≥0.5 mg/dl was required to be independently associated with increased in-hospital mortality among patients with baseline eGFR ≥60 ml/min per 1.73 m² (odds ratio [OR] 1.67; 95% confidence interval [CI] 1.13 to 2.47), 30 to 59 ml/min per 1.73 m² (OR 2.69; 95% CI, 1.82 to 3.97), and <30 ml/min per 1.73 m² (OR 2.15; 95% CI 1.02 to 4.51), respectively. There was a significant interaction between the nadir-to-peak sCr and baseline eGFR for in-hospital mortality (P < 0.001). Using these thresholds, survivors of AKI episodes had an increased hospital length of stay and were more likely to be discharged to a facility rather than home. Sensitivity analyses showed a significant interaction between baseline eGFR strata and relative increases in sCr, as well as absolute and relative decreases in eGFR for in-hospital mortality (P < 0.001).

Conclusions

This study suggests that future sCr-based definitions of AKI should take into consideration baseline eGFR.     

Fast Rate (≥ 250 bpm) Right Ventricular Burst Stimulation is Useful for Ventricular Tachycardia Induction in Arrhythmogenic Right Ventricular Cardiomyopathy

Background One of the major challenges in arrhythmogenic right ventricular cardiomyopathy (ARVC) ablation is ventricular tachycardia (VT) non-inducibility. The study aimed to assess whether fast rate (≥ 250 beats/min) right ventricular burst stimulation was useful for VT induction in patients with ARVC. Methods Ninety-one consecutive ARVC patients with clinical sustained VT that underwent electrophysiological study were enrolled. The stimulation protocol was implemented at both right ventricular apex and outflow tract as follows: Step A, up to double extra-stimuli; Step B, incremental stimulation with low rate (< 250 beats/min); Step C, burst stimulation with fast rate (≥ 250 beats/min); Step D, repeated all steps above with intravenous infusion of isoproterenol. Results A total of 76 patients had inducible VT (83.5%), among which 49 were induced by Step C, 15 were induced by Step B, 8 and 4 by Step A and D, respectively. Clinical VTs were induced in 60 patients (65.9%). Only two spontaneously ceased ventricular fibrillations were induced by Step C. Multivariate analysis showed that a narrower baseline QRS duration under sinus rhythm was independently associated with VT non-inducibility (OR: 1.1; 95% CI: 1.0–1.1; P = 0.019). Conclusion Fast rate (≥ 250 beats/min) right ventricular burst stimulation provides a useful supplemental method for VT induction in ARVC patients.     

Progression of Pediatric CKD of Nonglomerular Origin in the CKiD Cohort

Background and objectives

Congenital anomalies of the kidney and urinary tract and genetic disorders cause most cases of CKD in children. This study evaluated the relationships between baseline proteinuria and BP and longitudinal changes in GFR in children with these nonglomerular causes of CKD.

Design, setting, participants, & measurements

Urine protein-to-creatinine ratio, casual systolic and diastolic BP (normalized for age, sex, and height), and GFR decline were assessed in the prospective CKD in Children cohort study.

Results

A total of 522 children, median age 10 years (interquartile range, 7, 14 years) with nonglomerular CKD were followed for a median of 4.4 years. The mean baseline GFR in the cohort was 52 ml/min per 1.73 m² (95% confidence interval [95% CI], 50 to 54) and declined 1.3 ml/min per 1.73 m² per year on average (95%CI, 1.6 to 1.1). A 2-fold higher baseline urine protein-to-creatinine ratio was associated with an accelerated GFR decline of 0.3 ml/min per 1.73 m² per year (95% CI, 0.4 to 0.1). A 1-unit higher baseline systolic BP z-score was associated with an additional GFR decline of 0.4 ml/min per 1.73 m² per year (95% CI, 0.7 to 0.1). Among normotensive children, larger GFR declines were associated with larger baseline urine protein-to-creatinine ratios; eGFR declines of 0.8 and 1.8 ml/min per 1.73 m² per year were associated with urine protein-to-creatinine ratio <0.5 and ≥0.5 mg/mg, respectively. Among children with elevated BP, average GFR declines were evident but were not larger in children with higher levels of proteinuria.

Conclusions

Baseline proteinuria and systolic BP levels are independently associated with CKD progression in children with nonglomerular CKD.     

Albuminuria and Estimated Glomerular Filtration Rate as Predictors of Diabetic End-Stage Renal Disease and Death

Summary

Background and objectives

We investigated predictive value of albuminuria and estimated GFR (eGFR) for ESRD in Pima Indians with type 2 diabetes.

Design, setting, participants and measurements

Beginning in 1982, 2420 diabetic Pima Indians ≥18 years old were followed until they developed ESRD or died or until December 31, 2005. Individuals were classified at baseline by urinary albumin-to-creatinine ratio (ACR) and by eGFR, calculated by the Chronic Kidney Disease Epidemiology Collaboration equation. Predictors of ESRD and mortality were examined by proportional hazards regression.

Results

During a mean follow-up of 10.2 years, 287 individuals developed ESRD. Incidence of ESRD among individuals with macroalbuminuria (ACR ≥ 300 mg/g) was 9.3 times that of those with normoalbuminuria (ACR < 30 mg/g), controlled for age, gender, and duration of diabetes. Incidence among individuals with eGFR 15 to 29 ml/min per 1.73 m² was 81.9 times that of those with eGFR 90 to 119 ml/min per 1.73 m². Models that combined albuminuria and eGFR added significant predictive information about risk of ESRD or death compared with models containing eGFR or albuminuria alone. The hazard ratio for ESRD associated with a 10-ml/min per 1.73 m² lower eGFR was 1.36, whereas that associated with an increase in albuminuria category was 2.69; corresponding hazard ratios for death were 1.15 and 1.37.

Conclusions

These results suggest that incorporation of quantitative information about albuminuria into staging systems based on eGFR adds significant prognostic information about risk for diabetic ESRD and death.