Jerry Yee

Prevalence of Chronic Kidney Disease in US Adults with Undiagnosed Diabetes or Prediabetes

BACKGROUND AND OBJECTIVESnPrevalence of chronic kidney disease (CKD) in people with diagnosed diabetes is known to be high, but little is known about the prevalence of CKD in those with undiagnosed diabetes or prediabetes. We aimed to estimate and compare the community prevalence of CKD among people with diagnosed diabetes, undiagnosed diabetes, prediabetes, or no diabetes.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnThe 1999 through 2006 National Health and Nutrition Examination Survey is a representative survey of the civilian, noninstitutionalized US population. Participants who were aged > or =20 years; responded to the diabetes questionnaire; and had fasting plasma glucose (FPG), serum creatinine, and urinary albumin-creatinine ratio measurements were included (N = 8188). Diabetes status was defined as follows: Diagnosed diabetes, self-reported provider diagnosis (n = 826); undiagnosed diabetes, FPG > or =126 mg/dl without self-reported diagnosis (n = 299); prediabetes, FPG > or =100 and <126 mg/dl (n = 2272); and no diabetes, FPG <100 mg/dl (n = 4791). Prevalence of CKD was defined by estimated GFR 15 to 59 ml/min per 1.73 m(2) or albumin-creatinine ratio > or =30 mg/g; adjustment was performed with multivariable logistic regression.nnnRESULTSnFully 39.6% of people with diagnosed and 41.7% with undiagnosed diabetes had CKD; 17.7% with prediabetes and 10.6% without diabetes had CKD. Age-, gender-, and race/ethnicity-adjusted prevalence of CKD was 32.9, 24.2, 17.1, and 11.8%, for diagnosed, undiagnosed, pre-, and no diabetes, respectively. Among those with CKD, 39.1% had undiagnosed or prediabetes.nnnCONCLUSIONSnCKD prevalence is high among people with undiagnosed diabetes and prediabetes. These individuals might benefit from interventions aimed at preventing development and/or progression of both CKD and diabetes.

Chronic Kidney Disease Awareness Among Individuals with Clinical Markers of Kidney Dysfunction

BACKGROUND AND OBJECTIVESnAwareness of chronic kidney disease (CKD) among providers and patients is low. Whether clinical cues prompt recognition of CKD is unknown. We examined whether markers of kidney disease that should trigger CKD recognition among providers are associated with higher individual CKD awareness.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnCKD awareness was assessed in 1852 adults with an estimated GFR <60 ml/min per 1.73 m(2) using 1999 to 2008 National Health and Nutrition Examination Survey data. CKD awareness was a yes answer to Have you ever been told you have weak or failing kidneys? Participants were grouped by distribution of the following abnormal markers of CKD: hyperkalemia, acidosis, hyperphosphatemia, elevated blood urea nitrogen, anemia, albuminuria, and uncontrolled hypertension. Odds of CKD awareness associated with each abnormal marker and groupings of markers were estimated by multivariable logistic regression.nnnRESULTSnAmong individuals with kidney disease, only those with albuminuria had greater odds of CKD awareness (adjusted odds ratio, 4.0, P < 0.01) than those without. Odds of CKD awareness increased with each additional manifested clinical marker of CKD (adjusted odds ratio, 1.3, P = 0.05). Nonetheless, 90% of individuals with two to four markers of CKD and 84% of individuals with ≥5 markers of CKD were unaware of their disease.nnnCONCLUSIONSnAlthough individuals who manifest many markers of kidney dysfunction are more likely to be aware of their CKD, their CKD awareness remains low. A better understanding of mechanisms of awareness is required to facilitate earlier detection of CKD and implement therapy to minimize associated complications.

Acute Kidney Injury Recovery Pattern and Subsequent Risk of CKD: An Analysis of Veterans Health Administration Data

BACKGROUNDnStudies suggest an association between acute kidney injury (AKI) and long-term risk for chronic kidney disease (CKD), even following apparent renal recovery. Whether the pattern of renal recovery predicts kidney risk following AKI is unknown.nnnSTUDY DESIGNnRetrospective cohort.nnnSETTING & PARTICIPANTSnPatients in the Veterans Health Administration in 2011 hospitalized (> 24 hours) with at least 2 inpatient serum creatinine measurements, baseline estimated glomerular filtration rate > 60 mL/min/1.73 m², and no diagnosis of end-stage renal disease or non-dialysis-dependent CKD: 17,049 (16.3%) with and 87,715 without AKI.nnnPREDICTORnPattern of recovery to creatinine level within 0.3 mg/dL of baseline after AKI: within 2 days (fast), in 3 to 10 days (intermediate), and no recovery by 10 days (slow or unknown).nnnOUTCOMEnCKD stage 3 or higher, defined as 2 outpatient estimated glomerular filtration rates < 60 mL/min/1.73m² at least 90 days apart or CKD diagnosis, dialysis therapy, or transplantation.nnnMEASUREMENTSnRisk for CKD was modeled using modified Poisson regression and time to death-censored CKD was modeled using Cox proportional hazards regression, both stratified by AKI stage.nnnRESULTSnMost patients AKI episodes were stage 1 (91%) and 71% recovered within 2 days. At 1 year, 18.2% had developed CKD (AKI, 31.8%; non-AKI, 15.5%; P < 0.001). In stage 1, the adjusted relative risk ratios for CKD stage 3 or higher were 1.43 (95% CI, 1.39-1.48), 2.00 (95% CI, 1.88-2.12), and 2.65 (95% CI, 2.51-2.80) for fast, intermediate, and slow/unknown recovery. A similar pattern was observed in subgroup analyses incorporating albuminuria and sensitivity analysis of death-censored time to CKD.nnnLIMITATIONSnVariable timing of follow-up and mostly male veteran cohort may limit generalizability.nnnCONCLUSIONSnPatients who develop AKI during a hospitalization are at substantial risk for the development of CKD by 1 year following hospitalization and timing of AKI recovery is a strong predictor, even for the mildest forms of AKI.

Effects of Intensive BP Control in CKD

The appropriate target for BP in patients with CKD and hypertension remains uncertain. We report prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. We randomly assigned participants to a systolic BP target of <120 mm Hg (intensive group; n=1330) or <140 mm Hg (standard group; n=1316). After a median follow-up of 3.3 years, the primary composite cardiovascular outcome occurred in 112 intensive group and 131 standard group CKD participants (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.63 to 1.05). The intensive group also had a lower rate of all-cause death (HR, 0.72; 95% CI, 0.53 to 0.99). Treatment effects did not differ between participants with and without CKD (P values for interactions ≥0.30). The prespecified main kidney outcome, defined as the composite of ≥50% decrease in eGFR from baseline or ESRD, occurred in 15 intensive group and 16 standard group participants (HR, 0.90; 95% CI, 0.44 to 1.83). After the initial 6 months, the intensive group had a slightly higher rate of change in eGFR (-0.47 versus -0.32 ml/min per 1.73 m2 per year; P<0.03). The overall rate of serious adverse events did not differ between treatment groups, although some specific adverse events occurred more often in the intensive group. Thus, among patients with CKD and hypertension without diabetes, targeting an SBP<120 mm Hg compared with <140 mm Hg reduced rates of major cardiovascular events and all-cause death without evidence of effect modifications by CKD or deleterious effect on the main kidney outcome.

Association of sleep-related problems with CKD in the United States, 2005-2008

BACKGROUNDnSleep-related problems, which have been associated with poor health outcomes, have not been investigated thoroughly in people with chronic kidney disease (CKD). We examined the prevalence of a variety of sleep-related problems in persons with and without CKD.nnnSTUDY DESIGNnNational cross-sectional survey (National Health and Nutrition Examination Survey 2005-2008).nnnSETTING & PARTICIPANTSnCommunity-based survey of 9,110 noninstitutionalized US civilian residents 20 years or older.nnnPREDICTORnCKD, defined as estimated glomerular filtration rate (eGFR) of 15-59 mL/min/1.73 m(2) (stages 3 and 4) or eGFR ≥60 mL/min/1.73 m(2) and albumin-creatinine ratio ≥30 mg/g (stages 1 and 2).nnnOUTCOMEnSleep quality, defined using self-report in a multi-item sleep questionnaire including items from previously validated instruments.nnnMEASUREMENTSnAlbuminuria and eGFR assessed from urine and blood samples; sleep, demographics, and comorbid conditions assessed using a standardized questionnaire.nnnRESULTSnInadequate sleep (≤6 hours per night) differed by CKD severity (37.4%, 43.0%, and 30.9% for no CKD, CKD stages 1 and 2, and CKD stages 3 and 4, respectively; P = 0.003). Frequent sleeping pill use (8.4%, 9.9%, and 16.6%), leg symptoms (39.2%, 48.0%, and 50.9%), and nocturia (20.9%, 35.2%, and 43.6%; P < 0.001 for all) also differed by CKD severity. After adjustment for age, sex, race/ethnicity, obesity, diabetes, and cardiovascular disease, the prevalence of these sleep-related problems remained higher in people with CKD stages 1 and 2 relative to no CKD. Most other measures of sleep quality, disorder, and functional outcomes did not differ by CKD.nnnLIMITATIONSnInability to establish causality and possible unmeasured confounding.nnnCONCLUSIONnProviders should be aware of early sleep-related CKD manifestations, including inadequate sleep, leg symptoms, and nocturia, and of the high rate of reported sleep medication use in this population.

Nephrology care prior to end-stage renal disease and outcomes among new ESRD patients in the USA

Background Longer nephrology care before end-stage renal disease (ESRD) has been linked with better outcomes. Methods We investigated whether longer pre-end-stage renal disease (ESRD) nephrology care was associated with lower mortality at both the patient and state levels among 443 761 incident ESRD patients identified in the USA between 2006 and 2010. Results Overall, 33% of new ESRD patients had received no prior nephrology care, while 28% had received care for >12 months. At the patient level, predictors of >12 months of nephrology care included having health insurance, white race, younger age, diabetes, hypertension and US region. Longer pre-ESRD nephrology care was associated with lower first-year mortality (adjusted hazard ratio = 0.58 for >12 months versus no care; 95% confidence interval 0.57–0.59), higher albumin and hemoglobin, choice of peritoneal dialysis and native fistula and discussion of transplantation options. Living in a state with a 10% higher proportion of patients receiving >12 months of pre-ESRD care was associated with a 9.3% lower relative mortality rate, standardized for case mix (R2 = 0.47; P < 0.001). Conclusions This study represents the largest cohort of incident ESRD patients to date. Although we did not follow patients before ESRD onset, our findings, both at the individual patient and state levels, reflect the importance of early nephrology care among those with chronic kidney disease.

KDOQI US Commentary on the 2017 KDIGO Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD)

Chronic kidney disease-mineral and bone disorder (CKD-MBD) encompasses laboratory and bone abnormalities and vascular calcification and has deleterious effects on clinical outcomes. KDOQI (Kidney Disease Outcomes Quality Initiative), an initiative of the National Kidney Foundation, addressed this issue with the publication of a clinical practice guideline for bone metabolism and disease in CKD in 2003, and 2 years later, a new definition and classification scheme for CKD-MBD was developed following a KDIGO (Kidney Disease: Improving Global Outcomes) Controversies Conference. The initial KDIGO guideline on CKD-MBD was then published in 2009. New evidence was subsequently reviewed at the 2013 KDIGO Controversies Conference, andxa0in 2017, KDIGO issued a clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of CKD-MBD. This commentary presents the views of the KDOQI CKD-MBD work group convened byxa0the National Kidney Foundation. The KDOQI work group agrees with most of the KDIGO guideline update recommendations, particularly the suggestions regarding bone mineral density testing, joint assessments of longitudinal trends in mineral metabolism markers, and dietary phosphate counseling focused on phosphate additives. However, the KDOQI work group has some concerns about the suggestions related to hypocalcemia and hypercalcemia, phosphate-binder choice, and treatment of abnormal parathyroid hormone concentrations. The overall goal of this commentary is to provide a broad discussion for the US nephrology community regarding CKD-MBD and its diagnosis, prevention, and treatment.

Potential deaths averted and serious adverse events incurred from adoption of the SPRINT (systolic blood pressure intervention trial) intensive blood pressure regimen in the United States: Projections from NHANES (National Health and Nutrition Examination Survey)

Background —The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated a 27% reduction in all-cause mortality with a systolic blood-pressure (SBP) goal of Methods —SPRINT eligibility criteria were applied to the 1999-2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥ 50 years, SBP of 130-180 mmHg (depending on the number of antihypertensive medications being taken), and high CVD risk. Exclusion criteria were diabetes, history of stroke, >1 gram of proteinuria, heart failure, estimated glomerular filtration rate 2 , or dialysis. Annual mortality rates were calculated by dividing the Kaplan-Meier 5-year mortality by 5. Hazard ratios for all-cause mortality and heart failure and absolute risks for SAEs in SPRINT were used to estimate the number of potential deaths and heart failure cases prevented and SAEs incurred with intensive SBP treatment. Results —The mean age was 68.6 years and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95%CI 1.91%-2.48%) and intensive SBP treatment was projected to prevent about 107,500 deaths per year (95%CI 93,300-121,200) and give rise to 56,100 (95%CI 50,800-61,400) episodes of hypotension, 34,400 (95%CI 31,200-37,600) episodes of syncope, 43,400 (95%CI 39,400-47,500) serious electrolyte disorders, and 88,700 (95%CI 80,400-97,000) cases of acute kidney injury per year. The analysis of extremes approach indicated that the range of estimated lower and upper bound number of deaths prevented per year with intensive SBP control was 34,600 to 179,600. Intensive SBP control was projected to prevent 46,100 (95%CI 41,800-50,400) cases of heart failure annually. Conclusions —If fully implemented in eligible U.S. adults, intensive SBP treatment could prevent about 107,500 deaths per year. A consequence of this treatment strategy, however, could be an increase in SAEs.Background: SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal of <120 versus <140 mmu2009Hg among US adults at high cardiovascular disease risk but without diabetes mellitus, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events incurred if the SPRINT intensive SBP treatment goal were implemented in all eligible US adults. Methods: SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to 180 mmu2009Hg (depending on the number of antihypertensive medications being taken), and high cardiovascular disease risk. Exclusion criteria were diabetes mellitus, history of stroke, >1 g proteinuria, heart failure, estimated glomerular filtration rate <20 mL·min−1·1.73 m−2, or dialysis. Annual mortality rates were calculated by dividing the Kaplan-Meier 5-year mortality by 5. Hazard ratios for all-cause mortality and heart failure and absolute risks for serious adverse events in SPRINT were used to estimate the number of potential deaths and heart failure cases prevented and serious adverse events incurred with intensive SBP treatment. Results: The mean age was 68.6 years, and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95% confidence interval [CI], 1.91–2.48), and intensive SBP treatment was projected to prevent ≈107u2009500 deaths per year (95% CI, 93u2009300–121u2009200) and give rise to 56u2009100 (95% CI, 50u2009800–61u2009400) episodes of hypotension, 34u2009400 (95% CI, 31u2009200–37u2009600) episodes of syncope, 43u2009400 (95% CI, 39u2009400–47u2009500) serious electrolyte disorders, and 88u2009700 (95% CI, 80u2009400–97u2009000) cases of acute kidney injury per year. The analysis-of-extremes approach indicated that the range of estimated lower- and upper-bound number of deaths prevented per year with intensive SBP control was 34u2009600 to 179u2009600. Intensive SBP control was projected to prevent 46u2009100 (95% CI, 41u2009800–50u2009400) cases of heart failure annually. Conclusions: If fully implemented in eligible US adults, intensive SBP treatment could prevent ≈107u2009500 deaths per year. A consequence of this treatment strategy, however, could be an increase in serious adverse events.

Potential Deaths Averted and Serious Adverse Events Incurred From Adoption of the SPRINT (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen in the United StatesClinical Perspective

Background —The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated a 27% reduction in all-cause mortality with a systolic blood-pressure (SBP) goal of Methods —SPRINT eligibility criteria were applied to the 1999-2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥ 50 years, SBP of 130-180 mmHg (depending on the number of antihypertensive medications being taken), and high CVD risk. Exclusion criteria were diabetes, history of stroke, >1 gram of proteinuria, heart failure, estimated glomerular filtration rate 2 , or dialysis. Annual mortality rates were calculated by dividing the Kaplan-Meier 5-year mortality by 5. Hazard ratios for all-cause mortality and heart failure and absolute risks for SAEs in SPRINT were used to estimate the number of potential deaths and heart failure cases prevented and SAEs incurred with intensive SBP treatment. Results —The mean age was 68.6 years and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95%CI 1.91%-2.48%) and intensive SBP treatment was projected to prevent about 107,500 deaths per year (95%CI 93,300-121,200) and give rise to 56,100 (95%CI 50,800-61,400) episodes of hypotension, 34,400 (95%CI 31,200-37,600) episodes of syncope, 43,400 (95%CI 39,400-47,500) serious electrolyte disorders, and 88,700 (95%CI 80,400-97,000) cases of acute kidney injury per year. The analysis of extremes approach indicated that the range of estimated lower and upper bound number of deaths prevented per year with intensive SBP control was 34,600 to 179,600. Intensive SBP control was projected to prevent 46,100 (95%CI 41,800-50,400) cases of heart failure annually. Conclusions —If fully implemented in eligible U.S. adults, intensive SBP treatment could prevent about 107,500 deaths per year. A consequence of this treatment strategy, however, could be an increase in SAEs.Background: SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal of <120 versus <140 mmu2009Hg among US adults at high cardiovascular disease risk but without diabetes mellitus, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events incurred if the SPRINT intensive SBP treatment goal were implemented in all eligible US adults. Methods: SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to 180 mmu2009Hg (depending on the number of antihypertensive medications being taken), and high cardiovascular disease risk. Exclusion criteria were diabetes mellitus, history of stroke, >1 g proteinuria, heart failure, estimated glomerular filtration rate <20 mL·min−1·1.73 m−2, or dialysis. Annual mortality rates were calculated by dividing the Kaplan-Meier 5-year mortality by 5. Hazard ratios for all-cause mortality and heart failure and absolute risks for serious adverse events in SPRINT were used to estimate the number of potential deaths and heart failure cases prevented and serious adverse events incurred with intensive SBP treatment. Results: The mean age was 68.6 years, and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95% confidence interval [CI], 1.91–2.48), and intensive SBP treatment was projected to prevent ≈107u2009500 deaths per year (95% CI, 93u2009300–121u2009200) and give rise to 56u2009100 (95% CI, 50u2009800–61u2009400) episodes of hypotension, 34u2009400 (95% CI, 31u2009200–37u2009600) episodes of syncope, 43u2009400 (95% CI, 39u2009400–47u2009500) serious electrolyte disorders, and 88u2009700 (95% CI, 80u2009400–97u2009000) cases of acute kidney injury per year. The analysis-of-extremes approach indicated that the range of estimated lower- and upper-bound number of deaths prevented per year with intensive SBP control was 34u2009600 to 179u2009600. Intensive SBP control was projected to prevent 46u2009100 (95% CI, 41u2009800–50u2009400) cases of heart failure annually. Conclusions: If fully implemented in eligible US adults, intensive SBP treatment could prevent ≈107u2009500 deaths per year. A consequence of this treatment strategy, however, could be an increase in serious adverse events.

Potential Impact of Prescribing Metformin According to eGFR Rather Than Serum Creatinine

OBJECTIVE Many societies recommend using estimated glomerular filtration rate (eGFR) rather than serum creatinine (sCr) to determine metformin eligibility. We examined the potential impact of these recommendations on metformin eligibility among U.S. adults. RESEARCH DESIGN AND METHODS Metformin eligibility was assessed among 3,902 adults with diabetes who participated in the 1999–2010 National Health and Nutrition Examination Surveys and reported routine access to health care, using conventional sCr thresholds (eligible if <1.4 mg/dL for women and <1.5 mg/dL for men) and eGFR categories: likely safe, ≥45 mL/min/1.73 m2; contraindicated, <30 mL/min/1.73 m2; and indeterminate, 30–44 mL/min/1.73 m2). Different eGFR equations were used: four-variable MDRD, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine (CKD-EPIcr), and CKD-EPI cystatin C, as well as Cockcroft-Gault (CG) to estimate creatinine clearance (CrCl). Diabetes was defined by self-report or A1C ≥6.5% (48 mmol/mol). We used logistic regression to identify populations for whom metformin was likely safe adjusted for age, race/ethnicity, and sex. Results were weighted to the U.S. adult population. RESULTS Among adults with sCr above conventional cutoffs, MDRD eGFR ≥45 mL/min/1.73 m2 was most common among men (adjusted odds ratio [aOR] 33.3 [95% CI 7.4–151.5] vs. women) and non-Hispanic Blacks (aOR vs. whites 14.8 [4.27–51.7]). No individuals with sCr below conventional cutoffs had an MDRD eGFR <30 mL/min/1.73 m2. All estimating equations expanded the population of individuals for whom metformin is likely safe, ranging from 86,900 (CKD-EPIcr) to 834,800 (CG). All equations identified larger populations with eGFR 30–44 mL/min/1.73 m2, for whom metformin safety is indeterminate, ranging from 784,700 (CKD-EPIcr) to 1,636,000 (CG). CONCLUSIONS The use of eGFR or CrCl to determine metformin eligibility instead of sCr can expand the adult population with diabetes for whom metformin is likely safe, particularly among non-Hispanic blacks and men.