Juan D. Ordonez

Dialysis-requiring acute renal failure increases the risk of progressive chronic kidney disease

To determine whether acute renal failure (ARF) increases the long-term risk of progressive chronic kidney disease (CKD), we studied the outcome of patients whose initial kidney function was normal or near normal but who had an episode of dialysis-requiring ARF and did not develop end-stage renal disease within 30 days following hospital discharge. The study encompassed 556,090 adult members of Kaiser Permanente of Northern California hospitalized over an 8 year period, who had pre-admission estimated glomerular filtration rates (eGFR) equivalent to or greater than 45 ml/min/1.73 m(2) and who survived hospitalization. After controlling for potential confounders such as baseline level of eGFR and diabetes status, dialysis-requiring ARF was independently associated with a 28-fold increase in the risk of developing stage 4 or 5 CKD and more than a twofold increased risk of death. Our study shows that in a large, community-based cohort of patients with pre-existing normal or near normal kidney function, an episode of dialysis-requiring ARF was a strong independent risk factor for a long-term risk of progressive CKD and mortality.

The risk of acute renal failure in patients with chronic kidney disease.

Few studies have defined how the risk of hospital-acquired acute renal failure varies with the level of estimated glomerular filtration rate (GFR). It is also not clear whether common factors such as diabetes mellitus, hypertension and proteinuria increase the risk of nosocomial acute renal failure independent of GFR. To determine this we compared 1,746 hospitalized adult members of Kaiser Permanente Northern California who developed dialysis-requiring acute renal failure with 600,820 hospitalized members who did not. Patient GFR was estimated from the most recent outpatient serum creatinine measurement prior to admission. The adjusted odds ratios were significantly and progressively elevated from 1.95 to 40.07 for stage 3 through stage 5 patients (not yet on maintenance dialysis) compared to patients with estimated GFR in the stage 1 and 2 range. Similar associations were seen after controlling for inpatient risk factors. Pre-admission baseline diabetes mellitus, diagnosed hypertension and known proteinuria were also independent risk factors for acute kidney failure. Our study shows that the propensity to develop in-hospital acute kidney failure is another complication of chronic kidney disease whose risk markedly increases even in the upper half of stage 3 estimated GFR. Several common risk factors for chronic kidney disease also increase the peril of nosocomial acute kidney failure.

Nonrecovery of Kidney Function and Death after Acute on Chronic Renal Failure

BACKGROUND AND OBJECTIVES Relatively little is known about clinical outcomes, especially long-term outcomes, among patients who have chronic kidney disease (CKD) and experience superimposed acute renal failure (ARF; acute on chronic renal failure). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We tracked 39,805 members of an integrated health care delivery system in northern California who were hospitalized during 1996 through 2003 and had prehospitalization estimated GFR (eGFR) <45 ml/min per 1.73 m(2). Superimposed ARF was defined as having both a peak inpatient serum creatinine greater than the last outpatient serum creatinine by > or =50% and receipt of acute dialysis. RESULTS Overall, 26% of CKD patients who suffered superimposed ARF died during the index hospitalization. There was a high risk for developing ESRD within 30 d of hospital discharge that varied with preadmission renal function, being 42% among hospital survivors with baseline eGFR 30-44 ml/min per 1.73 m(2) and 63% among hospital survivors with baseline eGFR 15-29 ml/min per 1.73 m(2). Compared with patients who had CKD and did not experience superimposed ARF, those who did had a 30% higher long-term risk for death or ESRD. CONCLUSIONS In a large, community-based cohort of patients with CKD, an episode of superimposed dialysis-requiring ARF was associated with very high risk for nonrecovery of renal function. Dialysis-requiring ARF also seemed to be an independent risk factor for long-term risk for death or ESRD.

Risks for end-stage renal disease, cardiovascular events, and death in hispanic versus non-hispanic white adults with chronic kidney disease

Rates of ESRD are rising faster in Hispanic than non-Hispanic white individuals, but reasons for this are unclear. Whether rates of cardiovascular events and mortality differ among Hispanic and non-Hispanic white patients with chronic kidney disease (CKD) also is not well understood. Therefore, this study examined the associations between Hispanic ethnicity and risks for ESRD, cardiovascular events, and death in patients with CKD. A total of 39,550 patients with stages 3 to 4 CKD from Kaiser Permanente of Northern California were included. Hispanic ethnicity was obtained from self-report supplemented by surname matching. GFR was estimated from the abbreviated Modification of Diet in Renal Disease equation, and clinical outcomes, patient characteristics, and longitudinal medication use were ascertained from health plan databases and state mortality files. After adjustment for sociodemographic characteristics, Hispanic ethnicity was associated with an increased risk for ESRD (hazard ratio [HR] 1.93; 95% confidence interval [CI] 1.72 to 2.17) when compared with non-Hispanic white patients, which was attenuated after controlling for diabetes and insulin use (HR 1.50; 95% CI 1.33 to 1.69). After further adjustment for potential confounders, Hispanic ethnicity remained independently associated with an increased risk for ESRD (HR 1.33; 95% CI 1.17 to 1.52) as well as a lower risk for cardiovascular events (HR 0.82; 95% CI 0.76 to 0.88) and death (HR 0.72; 95% CI 0.66 to 0.79). Among a large cohort of patients with CKD, Hispanic ethnicity was associated with lower rates of death and cardiovascular events and a higher rate of progression to ESRD. The higher prevalence of diabetes among Hispanic patients only partially explained the increased risk for ESRD. Further studies are required to elucidate the cause(s) of ethnic disparities in CKD-associated outcomes.

Incident Atrial Fibrillation and Risk of End-Stage Renal Disease in Adults With Chronic Kidney Disease

Background— Atrial fibrillation (AF) frequently occurs in patients with chronic kidney disease (CKD). However, the long-term impact of development of AF on the risk of adverse renal outcomes in patients with CKD is unknown. In this study, we determined the association between incident AF and risk of end-stage renal disease (ESRD) among adults with CKD. Methods and Results— We studied adults with CKD (defined as estimated glomerular filtration rate eGFR <60 mL/min per 1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration equation) enrolled in Kaiser Permanente Northern California who were identified between 2002 and 2010 and who did not have previous ESRD or previously documented AF. Incident AF was identified by using primary hospital discharge diagnoses or 2 or more outpatient visits for AF. Incident ESRD was ascertained from a comprehensive health plan registry for dialysis and renal transplant. Among 206 229 adults with CKD, 16 463 developed incident AF. During a mean follow-up of 5.1±2.5 years, there were 345 cases of ESRD that occurred after development of incident AF (74 per 1000 person-years) in comparison with 6505 cases of ESRD during periods without AF (64 per 1000 person-years, P<0.001). After adjustment for potential confounders, incident AF was associated with a 67% increase in the rate of ESRD (hazard ratio, 1.67; 95% confidence interval, 1.46–1.91). Conclusions— Incident AF is independently associated with increased risk of developing ESRD in adults with CKD. Further study is needed to identify potentially modifiable pathways through which AF leads to a higher risk of progression to ESRD.

Elevated BP after AKI

The connection between AKI and BP elevation is unclear. We conducted a retrospective cohort study to evaluate whether AKI in the hospital is independently associated with BP elevation during the first 2 years after discharge among previously normotensive adults. We studied adult members of Kaiser Permanente Northern California, a large integrated health care delivery system, who were hospitalized between 2008 and 2011, had available preadmission serum creatinine and BP measures, and were not known to be hypertensive or have BP>140/90 mmHg. Among 43,611 eligible patients, 2451 experienced AKI defined using observed changes in serum creatinine concentration measured during hospitalization. Survivors of AKI were more likely than those without AKI to have elevated BP--defined as documented BP>140/90 mmHg measured during an ambulatory, nonemergency department visit--during follow-up (46.1% versus 41.2% at 730 days; P<0.001). This difference was evident within the first 180 days (30.6% versus 23.1%; P<0.001). In multivariable models, AKI was independently associated with a 22% (95% confidence interval, 12% to 33%) increase in the odds of developing elevated BP during follow-up, with higher adjusted odds with more severe AKI. Results were similar in sensitivity analyses when elevated BP was defined as having at least two BP readings of >140/90 mmHg or those with evidence of CKD were excluded. We conclude that AKI is an independent risk factor for subsequent development of elevated BP. Preventing AKI during a hospitalization may have clinical and public health benefits beyond the immediate hospitalization.

CKD and the Risk of Incident Cancer

Previous studies report a higher risk of cancer in patients with ESRD, but the impact of less severe CKD on risk of cancer is uncertain. Our objective was to evaluate the association between level of kidney function and subsequent cancer risk. We performed a retrospective cohort study of 1,190,538 adults who were receiving care within a health care delivery system, had a measurement of kidney function obtained between 2000 and 2008, and had no prior cancer. We examined the association between level of eGFR and the risk of incident cancer; the primary outcome was renal cancer, and secondary outcomes were any cancer and specific cancers (urothelial, prostate, breast, lung, and colorectal). During 6,000,420 person-years of follow-up, we identified 76,809 incident cancers in 72,875 subjects. After adjustment for time-updated confounders, lower eGFR (in milliliters per minute per 1.73 m(2)) was associated with an increased risk of renal cancer (adjusted hazard ratio [HR], 1.39; 95% confidence interval [95% CI], 1.22 to 1.58 for eGFR=45-59; HR, 1.81; 95% CI, 1.51 to 2.17 for eGFR=30-44; HR, 2.28; 95% CI, 1.78 to 2.92 for eGFR<30). We also observed an increased risk of urothelial cancer at eGFR<30 but no significant associations between eGFR and prostate, breast, lung, colorectal, or any cancer overall. In conclusion, reduced eGFR is associated with an independently higher risk of renal and urothelial cancer but not other cancer types.

Comparison of Type II and Type I Diabetics Treated for End-Stage Renal Disease in a Large Prepaid Health Plan Population

From 1978 through 1984, the incidence of treated end-stage renal disease (ESRD) secondary to diabetic nephropathy increased from 3 to 19 per million population among the membership of the Kaiser Permanente Medical Care Program in Northern California. Forty-eight percent had type II diabetes. Among 66 type II diabetics retinopathy was less severe and hypertension was more frequent than among 50 type I diabetics. Blacks were represented in a higher proportion than expected from their proportion of the health plan membership. Among type II diabetics who developed ESRD, once proteinuria occurred, nephropathy progressed at the same rate observed in type I diabetics. This observation suggests that the clinical progression of diabetic nephropathy may be similar for both types of diabetes after the development of proteinuria, but requires prospectively collected data for confirmation.

Incident Atrial Fibrillation and Risk of Death in Adults With Chronic Kidney Disease

Background Atrial fibrillation (AF) frequently occurs in patients with chronic kidney disease (CKD); however, the long‐term impact of development of AF on the risk of death among patients with CKD is unknown. Methods and Results We studied adults with CKD (glomerular filtration rate <60 mL/min per 1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration equation) identified between 2002 and 2010 who were enrolled in Kaiser Permanente Northern California and had no previously documented AF. Incident AF was identified using primary hospital discharge diagnoses or ≥2 outpatient visits for AF. Death was comprehensively ascertained from health plan administrative databases, Social Security Administration vital status files, and the California death certificate registry. Covariates included demographics, comorbidity, ambulatory blood pressure, laboratory values (hemoglobin, proteinuria), and longitudinal medication use. Among 81 088 adults with CKD, 6269 (7.7%) developed clinically recognized incident AF during a mean follow‐up of 4.8±2.7 years. There were 2388 cases of death that occurred after incident AF (145 per 1000 person‐years) compared with 18 865 cases of death during periods without AF (51 per 1000 person‐years, P<0.001). After adjustment for potential confounders, incident AF was associated with a 66% increase in relative rate of death (adjusted hazard ratio 1.66, 95% CI 1.57 to 1.77). Conclusion Incident AF is independently associated with an increased risk of death in adults with CKD. Further study is needed to understand the mechanisms by which CKD is associated with AF and to identify potentially modifiable risk factors to decrease the burden of AF and subsequent risk of death in this high‐risk population.

Epidemiologic features of treated end-stage renal disease in a large prepaid health plan.

We examined the incidence of treated end-stage renal disease (ESRD) among the two million members of the Kaiser Permanente Medical Care Program of Northern California from 1973 through 1985. The age-adjusted incidence rates rose from 33.9 to 81.7 per million person-years and showed no signs of stabilization. Rates were higher in men than in women and rose with age. Marked upward trends (p less than .001) in the rates of treated ESRD associated with diabetic nephropathy and hypertension were noted.