Chronic kidney disease (CKD) is the 16th leading cause of years of life lost worldwide. Appropriate screening, diagnosis, and management by primary care clinicians are necessary to prevent adverse ...CKD-associated outcomes, including cardiovascular disease, end-stage kidney disease, and death.
Defined as a persistent abnormality in kidney structure or function (eg, glomerular filtration rate GFR <60 mL/min/1.73 m2 or albuminuria ≥30 mg per 24 hours) for more than 3 months, CKD affects 8% to 16% of the population worldwide. In developed countries, CKD is most commonly attributed to diabetes and hypertension. However, less than 5% of patients with early CKD report awareness of their disease. Among individuals diagnosed as having CKD, staging and new risk assessment tools that incorporate GFR and albuminuria can help guide treatment, monitoring, and referral strategies. Optimal management of CKD includes cardiovascular risk reduction (eg, statins and blood pressure management), treatment of albuminuria (eg, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers), avoidance of potential nephrotoxins (eg, nonsteroidal anti-inflammatory drugs), and adjustments to drug dosing (eg, many antibiotics and oral hypoglycemic agents). Patients also require monitoring for complications of CKD, such as hyperkalemia, metabolic acidosis, hyperphosphatemia, vitamin D deficiency, secondary hyperparathyroidism, and anemia. Those at high risk of CKD progression (eg, estimated GFR <30 mL/min/1.73 m2, albuminuria ≥300 mg per 24 hours, or rapid decline in estimated GFR) should be promptly referred to a nephrologist.
Diagnosis, staging, and appropriate referral of CKD by primary care clinicians are important in reducing the burden of CKD worldwide.
Despite the availability of renal replacement therapy, acute kidney injury (AKI) is associated with high mortality and morbidity. In humans, it is difficult to determine whether AKI is a cause or ...consequence of excess morbidity. In animal models, however, it is increasingly clear that AKI induces distant organ dysfunction. Identified pathways include inflammatory cascades, apoptosis, the induction of remote oxidative stress, and differential molecular expression. Specifically, growing evidence implicates renal injury as an instigator and multiplier of pulmonary, cardiac, hepatic, and neurologic dysfunction. Accurate identification of these pathways will be critical in developing targeted therapies to improve outcomes in AKI. The purpose of this review is to summarize both clinical and preclinical studies of AKI and its role in distant organ injury.
Proton pump inhibitors (PPIs) are among the most commonly used drugs worldwide and have been linked to acute interstitial nephritis. Less is known about the association between PPI use and chronic ...kidney disease (CKD).
To quantify the association between PPI use and incident CKD in a population-based cohort.
In total, 10,482 participants in the Atherosclerosis Risk in Communities study with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m(2) were followed from a baseline visit between February 1, 1996, and January 30, 1999, to December 31, 2011. The data was analyzed from May 2015 to October 2015. The findings were replicated in an administrative cohort of 248,751 patients with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m(2) from the Geisinger Health System.
Self-reported PPI use in the Atherosclerosis Risk in Communities study or an outpatient PPI prescription in the Geisinger Health System replication cohort. Histamine2 (H2) receptor antagonist use was considered a negative control and active comparator.
Incident CKD was defined using diagnostic codes at hospital discharge or death in the Atherosclerosis Risk in Communities Study, and by a sustained outpatient estimated glomerular filtration rate of less than 60 mL/min/1.73 m(2) in the Geisinger Health System replication cohort.
Among 10,482 participants in the Atherosclerosis Risk in Communities study, the mean (SD) age was 63.0 (5.6) years, and 43.9% were male. Compared with nonusers, PPI users were more often of white race, obese, and taking antihypertensive medication. Proton pump inhibitor use was associated with incident CKD in unadjusted analysis (hazard ratio HR, 1.45; 95% CI, 1.11-1.90); in analysis adjusted for demographic, socioeconomic, and clinical variables (HR, 1.50; 95% CI, 1.14-1.96); and in analysis with PPI ever use modeled as a time-varying variable (adjusted HR, 1.35; 95% CI, 1.17-1.55). The association persisted when baseline PPI users were compared directly with H2 receptor antagonist users (adjusted HR, 1.39; 95% CI, 1.01-1.91) and with propensity score-matched nonusers (HR, 1.76; 95% CI, 1.13-2.74). In the Geisinger Health System replication cohort, PPI use was associated with CKD in all analyses, including a time-varying new-user design (adjusted HR, 1.24; 95% CI, 1.20-1.28). Twice-daily PPI dosing (adjusted HR, 1.46; 95% CI, 1.28-1.67) was associated with a higher risk than once-daily dosing (adjusted HR, 1.15; 95% CI, 1.09-1.21).
Proton pump inhibitor use is associated with a higher risk of incident CKD. Future research should evaluate whether limiting PPI use reduces the incidence of CKD.
Background Few trials of acute kidney injury (AKI) prevention after surgery have been conducted, and most observational studies focus on AKI following cardiac surgery. The frequency of, risk factors ...for, and outcomes after AKI following other types of major surgery have not been well characterized and may present additional opportunities for trials in AKI. Study Design Observational cohort study. Setting & Participants 3.6 million US veterans followed up from 2004 to 2011 for the receipt of major surgery (cardiac; general; ear, nose, and throat; thoracic; vascular; urologic; and orthopedic) and postoperative outcomes. Factors Demographics, health characteristics, and type of surgery. Outcomes Postoperative AKI defined by the KDIGO creatinine criteria, postoperative length of stay, end-stage renal disease, and mortality. Results Postoperative AKI occurred in 11.8% of the 161,185 major surgery hospitalizations (stage 1, 76%; stage 2, 15%, stage 3 without dialysis, 7%; and AKI requiring dialysis, 2%). Cardiac surgery had the highest postoperative AKI risk (relative risk RR, 1.22; 95% CI, 1.17-1.27), followed by general (reference), thoracic (RR, 0.92; 95% CI, 0.87-0.98), orthopedic (RR, 0.70; 95% CI, 0.67-0.73), vascular (RR, 0.68; 95% CI, 0.64-0.71), urologic (RR, 0.65; 95% CI, 0.61-0.69), and ear, nose, and throat (RR, 0.32; 95% CI, 0.28-0.37) surgery. Risk factors for postoperative AKI included older age, African American race, hypertension, diabetes mellitus, and, for estimated glomerular filtration rate < 90 mL/min/1.73 m2 , lower estimated glomerular filtration rate. Participants with postoperative AKI had longer lengths of stay (15.8 vs 8.6 days) and higher rates of 30-day hospital readmission (21% vs 13%), 1-year end-stage renal disease (0.94% vs 0.05%), and mortality (19% vs 8%), with similar associations by type of surgery and more severe stage of AKI relating to poorer outcomes. Limitations Urine output was not available to classify AKI; cohort included mostly men. Conclusions AKI was common after major surgery, with similar risk factor and outcome associations across surgery type. These results can inform the design of clinical trials in postoperative AKI to the noncardiac surgery setting.
Background Lifetime risk estimates of chronic kidney disease (CKD) can motivate preventative behaviors at the individual level and forecast disease burden and health care use at the population level. ...Study Design Markov Monte Carlo model simulation study. Setting & Population Current US black and white population. Model, Perspective, & Timeframe Markov models simulating kidney disease development, using an individual perspective and lifetime horizon. Outcomes Age-, sex-, and race-specific residual lifetime risks of CKD stages 3a+ (estimated glomerular filtration rate eGFR <60 mL/min/1.73 m2 ), 3b+ (eGFR <45 mL/min/1.73 m2 ), 4+ (eGFR <30 mL/min/1.73 m2 ), and end-stage renal disease (ESRD). Measurements State transition probabilities of developing CKD and of dying prior to its development were modeled using: (1) mortality rates from the National Vital Statistics Report, (2) mortality risk estimates from a 2-million person meta-analysis, and (3) CKD prevalence from National Health and Nutrition Examination Surveys. Incidence, prevalence, and mortality related to ESRD were supplied by the US Renal Data System. Results At birth, the overall lifetime risks of CKD stages 3a+, 3b+, 4+, and ESRD were 59.1%, 33.6%, 11.5%, and 3.6%, respectively. Women experienced greater CKD risk yet lower ESRD risk than men; blacks of both sexes had markedly higher CKD stage 4+ and ESRD risks (lifetime risks for white men, white women, black men, and black women, respectively: CKD stage 3a+, 53.6%, 64.9%, 51.8%, and 63.6%; CKD stage 3b+, 29.0%, 36.7%, 33.7%, and 40.2%; CKD stage 4+, 9.3%, 11.4%, 15.8%, and 18.5%; and ESRD, 3.3%, 2.2%, 8.5%, and 7.8%). Risk of CKD increased with age, with approximately one-half the CKD stage 3a+ cases developing after 70 years of age. Limitations CKD incidence was modeled from prevalence estimates in the US population. Conclusions In the United States, the lifetime risk of developing CKD stage 3a+ is high, emphasizing the importance of primary prevention and effective therapy to reduce CKD-related morbidity and mortality.
Background There are established guidelines for recommended dietary intake for hypertension treatment and cardiovascular disease prevention. Evidence is lacking for effective dietary patterns for ...kidney disease prevention. Study Design Prospective cohort study. Setting & Participants Atherosclerosis Risk in Communities (ARIC) Study participants with baseline estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 (N = 14,882). Predictor The Dietary Approaches to Stop Hypertension (DASH) diet score was calculated based on self-reported dietary intake of red and processed meat, sweetened beverages, sodium, fruits, vegetables, whole grains, nuts and legumes, and low-fat dairy products, averaged over 2 visits. Outcomes Cases were ascertained based on the development of eGFRs < 60 mL/min/1.73 m2 accompanied by ≥25% eGFR decline from baseline, an International Classification of Diseases, Ninth/Tenth Revision code for a kidney disease−related hospitalization or death, or end-stage renal disease from baseline through 2012. Results 3,720 participants developed kidney disease during a median follow-up of 23 years. Participants with a DASH diet score in the lowest tertile were 16% more likely to develop kidney disease than those with the highest score tertile (HR, 1.16; 95% CI, 1.07-1.26; P for trend < 0.001), after adjusting for sociodemographics, smoking status, physical activity, total caloric intake, baseline eGFR, overweight/obese status, diabetes status, hypertension status, systolic blood pressure, and antihypertensive medication use. Of the individual components of the DASH diet score, high red and processed meat intake was adversely associated with kidney disease and high nuts, legumes, and low-fat dairy products intake was associated with reduced risk for kidney disease. Limitations Potential measurement error due to self-reported dietary intake and lack of data for albuminuria. Conclusions Consuming a DASH-style diet was associated with lower risk for kidney disease independent of demographic characteristics, established kidney risk factors, and baseline kidney function. Healthful dietary patterns such as the DASH diet may be beneficial for kidney disease prevention.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are new medications that improve cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). However, the Food and Drug Administration ...has issued alerts regarding increased acute kidney injury (AKI) risk with canagliflozin and dapagliflozin. We aimed to assess the real-world risk of AKI in new SGLT2 inhibitor users in two large health care utilization cohorts of patients with T2D.
We used longitudinal data from the Mount Sinai chronic kidney disease registry and the Geisinger Health System cohort. We selected SGLT inhibitor users and nonusers (patients with T2D without SGLT2 inhibitor prescription). We determined AKI by the KDIGO (Kidney Disease: Improving Global Outcomes) definition (AKI
). We performed 1:1 nearest-neighbor propensity matching and calculated unadjusted hazard ratios (HRs) and adjusted HRs (aHRs; accounting for covariates poorly balanced) for AKI in primary and sensitivity analyses.
We identified 377 SGLT2 inhibitor users and 377 nonusers in the Mount Sinai cohort, of whom 3.8 and 9.7%, respectively, had an AKI
event over a median follow-up time of 14 months. The unadjusted hazards of AKI
were 60% lower in users (HR 0.4 95% CI 0.2-0.7;
= 0.01), which was unchanged (aHR 0.4 95% CI 0.2-0.7;
= 0.004) postadjustment. Similarly, we identified 1,207 SGLT2 inhibitor users and 1,207 nonusers in the Geisinger cohort, of whom 2.2 and 4.6% had an AKI
event. AKI
unadjusted hazards were lower in users (HR 0.5 95% CI 0.3-0.8;
< 0.01) with modest attenuation postadjustment for covariates (aHR 0.6 95% CI 0.4-1.1;
= 0.09). These estimates did not qualitatively change across several sensitivity analyses.
Our findings do not suggest an increased risk of AKI associated with SGLT2 inhibitor use in patients with T2D in two large health systems.
Dietary protein restriction is recommended for patients with moderate to severe renal insufficiency. Long-term data on the relationship between dietary protein sources and risk for incident kidney ...disease in individuals with normal kidney function are largely missing. This study aimed to assess the association between dietary protein sources and incident chronic kidney disease (CKD).
Prospective cohort.
Atherosclerosis Risk in Communities study participants from 4 US communities.
A total of 11,952 adults aged 44-66 years in 1987-1989 who were free of diabetes mellitus, cardiovascular disease, and had an estimated glomerular filtration rate (eGFR) ≥ 60 mL/minute/1.73 m
.
A 66-item food frequency questionnaire was used to assess food intake. CKD stage 3 was defined as a decrease in eGFR of ≥25% from baseline resulting in an eGFR of less than 60 mL/minute/1.73 m
; CKD-related hospitalization; CKD-related death; or end-stage renal disease. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression.
During a median follow-up of 23 years, there were 2,632 incident CKD cases. Red and processed meat consumption was associated with increased CKD risk (HR
: 1.23, 95% CI: 1.06-1.42, p
= 0.01). In contrast, higher dietary intake of nuts, legumes, and low-fat dairy products was associated with lower CKD risk (nuts: HR
: 0.81, 95% CI: 0.72-0.92, p
<0.001; low-fat dairy products: HR
: 0.75, 95% CI: 0.65-0.85, p
<0.001; legumes: HR
: 0.83, 95% CI: 0.72-0.95, p
= 0.03).
There were varied associations of specific dietary protein sources with risk of incident CKD; with red and processed meat being adversely associated with CKD risk; and nuts, low-fat dairy products, and legumes being protective against the development of CKD.
Improved understanding of genetic regulation of the proteome can facilitate identification of the causal mechanisms for complex traits. We analyzed data on 4,657 plasma proteins from 7,213 European ...American (EA) and 1,871 African American (AA) individuals from the Atherosclerosis Risk in Communities study, and further replicated findings on 467 AA individuals from the African American Study of Kidney Disease and Hypertension study. Here, we identified 2,004 proteins in EA and 1,618 in AA, with most overlapping, which showed associations with common variants in cis-regions. Availability of AA samples led to smaller credible sets and notable number of population-specific cis-protein quantitative trait loci. Elastic Net produced powerful models for protein prediction in both populations. An application of proteome-wide association studies to serum urate and gout implicated several proteins, including IL1RN, revealing the promise of the drug anakinra to treat acute gout flares. Our study demonstrates the value of large and diverse ancestry study to investigate the genetic mechanisms of molecular phenotypes and their relationship with complex traits.
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