James F. Simon

Serum Bicarbonate and Mortality in Stage 3 and Stage 4 Chronic Kidney Disease

BACKGROUND AND OBJECTIVES The incidence and prevalence of metabolic acidosis increase with declining kidney function. We studied the associations of both low and high serum bicarbonate levels with all-cause mortality among stage 3 and 4 chronic kidney disease (CKD) patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We examined factors associated with low (<23 mmol/L) and high (>32 mmol/L) serum bicarbonate levels using logistic regression models and associations between bicarbonate and all-cause mortality using Cox-proportional hazard models, Kaplan-Meier survival curves, and time-dependent analysis. RESULTS Out of 41,749 patients, 13.9% (n = 5796) had low and 1.6% (n = 652) had high serum bicarbonate levels. After adjusting for relevant covariates, there was a significant association between low serum bicarbonate and all-cause mortality (hazard ratio [HR] 1.23, 95% CI 1.16, 1.31). This association was not statistically significant among patients with stage 4 CKD and diabetes. The time-dependent analysis demonstrated a significant mortality risk associated with a decline from normal to low bicarbonate level (HR 1.59, 95% CI 1.49, 1.69). High serum bicarbonate levels were associated with death irrespective of the level of kidney function (HR 1.74, 95% CI 1.52, 2.00). When serum bicarbonate was examined as a continuous variable, a J-shaped relationship was noted between serum bicarbonate and mortality. CONCLUSIONS Low serum bicarbonate levels are associated with increased mortality among stage 3 CKD patients and patients without diabetes. High serum bicarbonate levels are associated with mortality in both stage 3 and stage 4 CKD patients.

Development and Validation of an Electronic Health Record–Based Chronic Kidney Disease Registry

BACKGROUND AND OBJECTIVES Chronic kidney disease (CKD) is increasing, and outcomes-related research from diverse health care settings is needed to target appropriate efforts and interventions. We developed an electronic health record (EHR)-based CKD registry at the Cleveland Clinic and validated comorbid conditions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients who had at least one face-to-face outpatient encounter with a Cleveland Clinic health care provider and (1) had two estimated GFR values <60 ml/min per 1.73 m(2) >90 days apart as of January 1, 2005 and/or (2) were patients with International Classification of Diseases-9 (ICD-9) diagnosis codes for kidney disease were included. RESULTS Our registry includes 57,276 patients (53,399 patients met estimated GFR criteria and 3877 patients met ICD-9 diagnosis code criteria) as of March 2010. Mean age was 69.5 ± 13.4 years, with 55% women and 12% African Americans. Medicare is the primary insurer for more than one half of the study cohort. The κ statistics to assess the extent of agreement between the administrative dataset extracted from the EHR and actual EHR chart review showed substantial agreement (>0.80) for all conditions except for coronary artery disease and hypertension, which had moderate agreement (<0.60). CONCLUSIONS Development of an EHR-based CKD registry is feasible in a large health system, and the comorbid conditions included in the registry are reliable. In addition to conducting research studies, such a registry could help to improve the quality of care delivered to CKD patients and complement the ongoing nationwide efforts to develop a CKD surveillance project.

Low 25-Hydroxyvitamin D Levels and Mortality in Non–Dialysis-Dependent CKD

BACKGROUND Low 25-hydroxyvitamin D (25[OH]D) levels are common in patients with non-dialysis-dependent chronic kidney disease (CKD). The associations between low 25(OH)D levels and mortality in non-dialysis-dependent patients with CKD are unclear. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS Patients with stages 3-4 CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m(2); n = 12,673) who had 25(OH)D levels measured after the diagnosis of CKD in the Cleveland Clinic Health System. PREDICTOR 25(OH)D levels categorized into 3 groups: <15, 15-29, and ≥30 ng/mL. OUTCOMES We examined factors associated with low 25(OH)D levels and associations between low 25(OH)D levels and all-cause mortality (ascertained using the Social Security Death Index and our electronic medical record) using logistic regression, Cox proportional hazard models, and Kaplan-Meier survival curves. MEASUREMENTS 25(OH)D was measured using chemiluminescence immunoassay. RESULTS Of 12,763 patients with CKD, 15% (n = 1,970) had 25(OH)D levels <15 ng/mL, whereas 45% (n = 5,749) had 25(OH)D levels of 15-29 ng/mL. Male sex, African American race, diabetes, coronary artery disease, and lower estimated glomerular filtration rate were associated significantly with 25(OH)D level <30 ng/mL. A graded increase in risk of 25(OH)D level <30 ng/mL was evident across increasing body mass index levels. Patients who had 25(OH)D levels measured in fall through spring had higher odds for 25(OH)D levels <30 ng/mL. After covariate adjustment, patients with CKD with 25(OH)D levels <15 ng/mL had a 33% increased risk of mortality (95% CI, 1.07-1.65). The group with 25(OH)D levels of 15-29 ng/mL did not show a significantly increased risk of mortality (HR, 1.03; 95% CI, 0.86-1.22) compared with patients with 25(OH)D levels ≥30 ng/mL. LIMITATIONS Single-center observational study, lack of data for albuminuria and other markers of bone and mineral disorders, and attrition bias. CONCLUSIONS 25(OH)D level <15 ng/mL was associated independently with all-cause mortality in non-dialysis-dependent patients with CKD.

Prognostic Importance of Serum Alkaline Phosphatase in CKD Stages 3-4 in a Clinical Population

BACKGROUND Elevated total serum alkaline phosphatase (ALP) levels have been associated with mortality in the general population and in dialysis patients. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS 28,678 patients with chronic kidney disease (CKD) stages 3 and 4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m(2)) were identified using the Cleveland Clinic CKD Registry. CKD was defined as 2 estimated glomerular filtration rate values <60 mL/min/1.73 m(2) drawn more than 90 days apart using the CKD-EPI (CKD Epidemiology Collaboration) creatinine equation. PREDICTOR ALP levels measured using the calorimetric assay were examined as quartiles (quartile [Q]1, <66 U/L; Q2, 66-81 U/L; Q3, 82-101 U/L; and Q4, ≥102 U/L) and as a continuous measure. OUTCOMES & MEASUREMENTS All-cause mortality and end-stage renal disease (ESRD) were ascertained using the Social Security Death Index and US Renal Data System. RESULTS After a median follow-up of 2.2 years, 588 patients progressed to ESRD and 4,755 died. There was a graded increase in risk of mortality with higher ALP quartiles (Q2, Q3, and Q4) compared to the reference quartile (Q1) after adjusting for demographics, comorbid conditions, use of relevant medications, and liver function test results. The highest ALP quartile was associated with an HR for ESRD of 1.38 (95% CI, 1.09-1.76). Each 1-SD (42.7 U/L) higher ALP level was associated with 15% (95% CI, 1.09-1.22) and 16% (95% CI, 1.14-1.18) increased risk of ESRD and mortality, respectively. LIMITATIONS Single-center observational study; lack of complete data, including parathyroid hormone level, for all study participants, and attrition bias. CONCLUSIONS Higher serum ALP levels in patients with CKD stages 3-4 were associated independently with all-cause mortality and ESRD.

Implications of the CKD-EPI GFR estimation equation in clinical practice.

BACKGROUND AND OBJECTIVES Chronic kidney disease (CKD) is a significant public health problem whose diagnosis and staging relies upon GFR-estimating equations, including the new CKD-EPI equation. CKD-EPI demonstrated superior performance compared with the existing MDRD equation but has not been applied to a healthcare system. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We identified 53,759 patients with stages 3 to 5 CKD on the basis of either MDRD or CKD-EPI equations using two eGFR values <60 ml/min per 1.73 m² > 90 days apart from an outpatient setting. We compared patient characteristics, presence of related diagnosis codes, and time CKD classification between equations. RESULTS The number of patients identified with CKD decreased 10% applying CKD-EPI versus MDRD. Changes varied substantially by patient characteristics including a 35% decrease among patients < 60 years and a 10% increase among patients > 90 years. Women, non-African Americans, nondiabetics, and obese patients were less likely to be classified on the basis of CKD-EPI. Time to CKD classification was significantly longer with CKD-EPI among younger patients. 14% of patients identified with CKD on the basis of either estimating equation also had a related ICD-9 diagnosis, ranging from 19% among patients < 60 years to 7% among patients > 90 years. CONCLUSIONS Consistent with findings in the general population, CKD-EPI resulted in substantial declines in equation-based CKD diagnoses in a large healthcare system. Further research is needed to determine whether widespread use of CKD-EPI with current guidelines could lead to delayed needed care among younger patients or excessive referrals among older patients.

Stenting atherosclerotic renal arteries: time to be less aggressive.

Percutaneous intervention has become very popular for treating atherosclerotic renal artery stenosis, as the use of stents has boosted the rate of technical success and as more cases are being discovered incidentally during angiography of the coronary or other arteries. Yet randomized trials indicate that the procedure does little in terms of controlling blood pressure and may actually harm as many patients as it helps in terms of renal function. Needed are better ways to predict which patients will benefit and better ways to prevent adverse effects such as atheroembolism. It is time to strongly reconsider the current aggressive approach to revascularization of stenotic renal arteries and to take a more coordinated, critical approach.

Interpreting the estimated glomerular filtration rate in primary care: Benefits and pitfalls

As several equations have been developed for estimating the glomerular filtration rate (GFR), many laboratories are now reporting the GFR automatically, and primary care providers are left trying to interpret the results and put them into the context of patient care. Therefore, it is important that health care professionals understand how to interpret the estimated GFR value and how to recognize when the estimate may not be accurate. Many laboratories are now reporting the glomerular filtration rate automatically, and primary care providers are left trying to interpret the results.

Chronic kidney disease in an electronic health record problem list: quality of care, ESRD, and mortality.

Background: Whether chronic kidney disease (CKD) recognition in an electronic health record (EHR) problem list improves processes of care or clinical outcomes of end-stage renal disease (ESRD) and death is unclear. Methods: We identified patients who had at least 1 year of follow-up (2005-2009) in our EHR-based CKD registry (n = 25,742). CKD recognition was defined by having ICD-9 codes for CKD, diabetic kidney disease, or hypertensive kidney disease in the problem list. We calculated proportions of patients with and without CKD recognition and examined differences by demographics, clinical factors, and development of ESRD or mortality. We evaluated differences in the proportion of patients with CKD-specific laboratory results checked before and after recognition among cases and propensity-matched controls. Results: Only 11% (n = 2,735) had CKD recognition in the problem list and they were younger (68 vs. 71 years), a higher proportion were male (61 vs. 37%) and African-American (21 vs. 10%) compared to those unrecognized. CKD-specific laboratory results for patients with estimated glomerular filtration rate (eGFR) 30-59 including intact parathyroid hormone (23 vs. 6%), vitamin D (22 vs. 18%), phosphorus (29 vs. 7%), and a urine check for proteinuria (55 vs. 36%) were significantly more likely to be done among those with CKD recognition (all p < 0.05). Similar results were found for eGFR <30 except for proteinuria and in our propensity score-matched control analysis. There was no independent association of CKD recognition with ESRD or mortality. Conclusions: CKD recognition in the EHR problem list was low, but translated into more CKD-specific processes of care; however ESRD or mortality were not affected.

IgA-dominant Staphylococcus infection-associated glomerulonephritis: case reports and review of the literature

Background and objectives. The mesangial deposition of IgA is rarely described with proliferative glomerulonephritis associated with Staphylococcus infection. Recently, this association has been increasingly recognized possibly due to the increased rate of Staphylococcus infection. Design setting, participants and measurements. We report two cases of methicillin-sensitive Staphylococcus aureus bacteremia associated with acute proliferative glomerulonephritis with dominant mesangial deposit of IgA. We searched MEDLINE (1960–2009) for similar reports. We pooled individual patient data and reported descriptive statistics of all published cases. Results. Forty-six cases were included in the final analysis. The mean age of presentation was 59, with a male predominance (84%). Clinical presentation was notable for rapidly progressive glomerulonephritis with nephrotic-range proteinuria and normal complement levels in 52 and 72%, respectively. Methicillin-resistant S. aureus (68%) was the most common pathogen isolated with a latent period ranging from 1 to 16 weeks. Diffuse mesangial proliferation was commonly found with crescentic lesions noted in 35% of the cases. Antimicrobial treatment was associated with renal recovery in 58% of the cases. Need for renal replacement therapy was significantly associated with pre-existing diabetes, hypertension and interstitial fibrosis seen on kidney biopsy. Conclusions. IgA-dominant post-Staphylococcus glomerulonephritis is a rare clinical entity with certain unique clinical and morphologic features. It is difficult to differentiate from primary IgA nephropathy in cases where the infection is not apparent. An acute onset of rapidly progressive glomerulonephritis, with normal complement levels and deposition of mesangial IgA in an elderly patient should raise suspicion for this rare form of glomerulonephritis.

Managing advanced chronic kidney disease: A primary care guide

Chronic kidney disease (CKD) is a common disorder that requires close collaboration between the primary care physician and nephrologist. Most aspects of early CKD can be managed in the primary care setting with nephrology input. As the disease progresses, many aspects of care should be transitioned to the nephrologist, especially as the patient nears end-stage renal disease, when dialysis and transplantation must be addressed. Primary care physicians can manage most aspects early on, but as it progresses, more care should shift to a nephrologist.