Background The purpose of this study is to evaluate serum bicarbonate as a risk factor for renal outcomes, cardiovascular events and mortality in patients with chronic kidney disease (CKD). Study Design Observational cohort study. Setting & Participants 3939 participants with CKD stages 2-4 who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) between June 2003 - December 2008. Predictor Serum bicarbonate. Outcomes Renal outcomes, defined as end-stage renal disease (either initiation of dialysis or kidney transplantation) or 50% reduction in eGFR; atherosclerotic events (myocardial infarction, stroke, peripheral arterial disease); congestive heart failure events; and death. Measurements Time to event. Results The mean eGFR was 44.8 ± 16.8 (SD) mL/min/1.73 m2, and the median serum bicarbonate was 24 (IQR, 22-26) mEq/L. During a median follow-up of 3.9 years, 374 participants died, 767 had a renal outcome, and 332 experienced an atherosclerotic event and 391 had a congestive heart failure event. In adjusted analyses, the risk of developing a renal endpoint was 3% lower per mEq/L increase in serum bicarbonate (HR, 0.97; 95% CI, 0.94-0.99; p=0.01). The association was stronger for participants with eGFR> 45ml/min/1.73m2 (HR, 0.91; 95%CI, 0.85-0.97; p=0.004). The risk of heart failure increased by 14% (HR, 1.14; 95%CI, 1.03-1.26; p=0.02) per mEq/L increase in serum bicarbonate over 24 mEq/L. Serum bicarbonate was not independently associated with atherosclerotic events (HR, 0.99; 95%CI, 0.95-1.03; p=0.6) and all-cause mortality (HR, 0.98; 95%CI, 0.95-1.02; p=0.3). Limitations Single measurement of sodium bicarbonate. Conclusions In a cohort of participants with CKD, low serum bicarbonate was an independent risk factor for kidney disease progression, particularly for participants with preserved kidney function. The risk of heart failure was higher at the upper extreme of serum bicarbonate. There was no association between serum bicarbonate and all-cause mortality or atherosclerotic events.

Background and objectives Masked hypertension and elevated nighttime BP are associated with increased risk of hypertensive target organ damage and adverse cardiovascular and renal outcomes in patients with normal kidney function. The significance of masked hypertension for these risks in patients with CKD is less well defined. The objective of this study was to evaluate the association between masked hypertension and kidney function and markers of cardiovascular target organ damage, and to determine whether this relationship was consistent among those with and without elevated nighttime BP.Design, setting, participants, & measurements This was a cross-sectional study. We performed 24-hour ambulatory BP in 1492 men and women with CKD enrolled in the Chronic Renal Insufficiency Cohort Study. We categorized participants into controlled BP, white-coat, masked, and sustained hypertension on the basis of clinic and 24-hour ambulatory BP. We obtained echocardiograms and measured pulse wave velocity in 1278 and 1394 participants, respectively. ResultsThe percentages of participants with controlled BP, white-coat, masked, and sustained hypertension were 49.3%, 4.1%, 27.8%, and 18.8%, respectively. Compared with controlled BP, masked hypertension independently associated with low eGFR (23.2 ml/min per 1.73 m 2 ; 95% confidence interval, 25.5 to 20.9), higher proteinuria (+0.9 unit higher in log 2 urine protein; 95% confidence interval, 0.7 to 1.1), and higher left ventricular mass index (+2.52 g/m 2.7 ; 95% confidence interval, 0.9 to 4.1), and pulse wave velocity (+0.92 m/s; 95% confidence interval, 0.5 to 1.3). Participants with masked hypertension had lower eGFR only in the presence of elevated nighttime BP (23.6 ml/min per 1.73 m 2 ; 95% confidence interval, 26.1 to 21.1; versus 21.4 ml/min per 1.73 m 2 ; 95% confidence interval, 26.9 to 4.0, among those with nighttime BP ,120/70 mmHg; P value for interaction with nighttime systolic BP 0.002).Conclusions Masked hypertension is common in patients with CKD and associated with lower eGFR, proteinuria, and cardiovascular target organ damage. In patients with CKD, ambulatory BP characterizes the relationship between BP and target organ damage better than BP measured in the clinic alone.

The association between apparent treatment resistant hypertension (ATRH) and clinical outcomes is not well studied in chronic kidney disease (CKD). We analyzed data on 3367 hypertensive participants in the Chronic Renal Insufficiency Cohort (CRIC) to determine prevalence, associations, and clinical outcomes of ATRH in non-dialysis CKD patients. ATRH was defined as blood pressure (BP) ≥140/90 mm Hg on ≥3 antihypertensives, or use of ≥4 antihypertensives with BP at goal at baseline visit. Prevalence of ATRH was 40.4%. Older age, male gender, black race, diabetes, and higher BMI were independently associated with higher odds of having ATRH. Participants with ATRH had a higher risk of clinical events compared to participants without ATRH - composite of myocardial infarction (MI), stroke, peripheral arterial disease (PAD), congestive heart failure (CHF), and all-cause mortality HR [95% CI]: (1.38 [1.22,1.56]); renal events (1.28 [1.11, 1.46]); CHF (1.66 [1.38, 2.00]); and all-cause mortality (1.24 [1.06,1.45]). The subset of participants with ATRH and BP at goal on ≥ 4 medications also had higher risk for composite of MI, stroke, PAD, CHF, and all-cause mortality HR [95% CI] (1.30 [1.12, 1.51]) and CHF (1.59 [1.28, 1.99]) compared to those without ATRH. ATRH was associated with significantly higher risk for CHF and renal events only among those with eGFR ≥30 ml/min/1.73 m2. Our findings show that ATRH is common and associated with high risk of adverse outcomes in a cohort of patients with CKD. This underscores the need for early identification and management of patients with ATRH and CKD.

Design We introduced a long-term care facility (LTCF) Infectious Disease (ID) consult service (LID) that provides on-site consultations to residents of a VA LTCF. We determined the impact of the LID service on antimicrobial use and Clostridium difficile infections at the LTCF. Setting A 160-bed Veterans Affairs (VA) LTCF. Methods Systemic antimicrobial use and the rate of positive C. difficile tests at the LTCF were compared for 36 months before and 18 months after the initiation of the ID consultation service using segmented regression analysis of an interrupted time-series. Results In contrast to the pre-intervention period, total systemic antibiotic administration decreased by 30% (P <.001) with a significant reduction in both oral (32%; P<.001) and intravenous agents (25%; P =.008). The greatest reductions were seen for tetracyclines (64%, P <.001), clindamycin (61%; P <.001), sulfamethoxazole/trimethoprim (38%; P <.001), fluoroquinolones (38%; P <.001) and beta-lactam/beta-lactamase inhibitor combinations (28%; P <.001). Rates of change for positive C. difficile tests at the LTCF declined in the post- vs. preintervention periods (P = .04). Conclusions Implementation of a LTCF ID service led to a significant reduction in total antimicrobial use. Bringing providers with infectious disease expertise to the LTCF represents a new and effective means to achieve antimicrobial stewardship.

Background Early and late readmissions may have different causal factors and thus require different strategies for prevention. Objective Determine whether predictors of readmission change within the 30-day window post-discharge. Design Retrospective cohort study Setting Academic medical center Participants Medicine discharges, 1/1/2009-12/31/2010 Exposures (1) Factors related to the index hospitalization: acute illness burden, inpatient care process factors, and clinical indicators of instability at discharge; (2) Unrelated factors: chronic illness burden, and social determinants of health. Outcomes (1) Early readmissions, 0-7d post-discharge; (2) Late readmissions, 8-30d post-discharge. Results 13,334 discharges, representing 8,078 patients were included in the analysis, 1,046 readmissions (7.8%) occurred in the early period and 1,586 readmissions (11.9%) occurred in the late period. Early readmissions were associated with markers of acute illness burden, including length of hospital stay (Odds Ratio(OR) 1.02, 95%CI 1.00-1.03), and whether a rapid response team assessment was called (OR1.48, 95%CI 1.15-1.89); some markers of chronic illness burden, including being on a medication that indicates organ failure (OR1.19 95%CI 1.02-1.40); and some social determinants of health, including barriers to learning (OR 1.18 95%CI 1.01-1.38); and were less likely if a patient was discharged from the hospital between 800AM-1259 PM (OR0.76, 95%CI 0.58-0.99). Late readmissions were associated with markers of chronic illness burden, including being on a medication that indicated organ failure (OR1.27, 95%CI 1.10-1.46) or hemodialysis (OR1.75, 95%CI 1.29-2.37); and social determinants of health, including barriers to learning (OR1.22, 95%CI 1.07-1.40), and having unsupplemented Medicare or Medicaid (OR1.20, 95%CI 1.04-1.38). Limitations Single center, only ascertains readmissions at our institution Conclusions The 30 days following hospital discharge may not be homogeneous. Causal factors and readmission prevention strategies may be different for the early vs. late periods. Primary Funding Source Health Resources and Services Administration training grant [T32 HP12706].

APOL1 risk variants are associated with kidney disease in blacks, but the mechanisms of renal injury associated with APOL1 risk variants are unknown. Because APOL1 is unique to humans and some primates, we created transgenic (Tg) mice using the promoter of nephrin-encoding Nphs1 to express the APOL1 reference sequence (G0) or the G2 risk variant in podocytes, establishing Tg lines with a spectrum of APOL1 expression levels. Podocytes from Tg-G0 and Tg-G2 mice did not undergo necrosis, apoptosis, or autophagic cell death in vivo, even in lines with highly expressed transgenes. Further, Tg-G0 and Tg-G2 mice did not develop kidney pathology, proteinuria, or azotemia as of 300 days of age. However, by 200 days of age, Tg-G2 mice had significantly lower podocyte density than age-matched WT and Tg-G0 mice had, a difference that was not evident at weaning. Notably, a pregnancy-associated phenotype that encompassed eclampsia, preeclampsia, fetal/neonatal deaths, and small litter sizes occurred in some Tg-G0 mice and more severely in Tg-G2 mice. Similar to human placenta, placentas of Tg mice expressed APOL1. Overall, these results suggest podocyte depletion could predispose individuals with APOL1 risk genotypes to kidney disease in response to a second stressor, and add to other published evidence associating APOL1 expression with preeclampsia.

Registered at ClinicalTrials.gov with study number NCT01206062.

Background and objectives Sickle cell disease (SCD) is an inherited anemia that afflicts millions worldwide. Kidney disease is a major contributor to its morbidity and mortality. We examined contemporary and historical SCD populations to understand how renal disease behaved in hemoglobin SS (HbSS) compared with HbSC. . Macroalbuminuria was seen in 20% of participants with SCD (HbSS or HbSC; P=0.45; Walk-PHaSST Trial), but microalbuminuria was more prevalent in HbSS (44% versus 23% in HbSC; P,0.002). In the Walk-PHaSST Trial, albuminuria was associated with hemolysis (higher lactate dehydrogenase, P,0.001; higher absolute reticulocyte count, P,0.02; and lower Hb, P=0.07) and elevated systolic BP (P,0.001) in HbSS. One half of all participants with HbSS (20 of 39) versus one fifth without (41 of 228) elevated tricuspid regurgitant jet velocity ($3 m/s; adverse prognostic indicator in SCD) had macroalbuminuria (P,0.001). In the CSSCD, overt proteinuria, detected (less sensitively) by urine dipstick, associated with higher 3-year mortality (odds ratio, 2.48; 95% CI, 1.07 to 5.77). Serum bicarbonate was lower in HbSS (23.8 versus 24.8 mEq/dl in HbSC; P,0.05) and associated with reticulocytopenic anemia and decreased renal function.Conclusions In SCD, albuminuria or proteinuria was highly prevalent, in HbSS more than in HbSC. Proteinuria associated with mortality in HbSS. Older individuals had a lower than expected eGFR, and this was more prominent in HbSS. Current management does not routinely address renal complications in SCD, which could plausibly reduce morbidity and mortality.