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 m2 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.

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.

There is limited information about the true incidence of acute renal failure (ARF). Most studies could not quantify disease frequency in the general population as they are hospital-based and confounded by variations in threshold and the rate of hospitalization. Earlier studies relied on diagnostic codes to identify non-dialysis requiring ARF. These underestimated disease incidence since the codes have low sensitivity. Here we quantified the incidence of non-dialysis and dialysis-requiring ARF among members of a large integrated health care delivery system - Kaiser Permanente of Northern California. Non-dialysis requiring ARF was identified using changes in inpatient serum creatinine values. Between 1996 and 2003, the incidence of non-dialysis requiring ARF increased from 322.7 to 522.4 whereas that of dialysis-requiring ARF increased from 19.5 to 29.5 per 100,000 person-years. ARF was more common in men and among the elderly, although those aged 80 years or more were less likely to receive acute dialysis treatment. We conclude that the use of serum creatinine measurements to identify cases of non-dialysis requiring ARF resulted in much higher estimates of disease incidence compared with previous studies. Both dialysis-requiring and non-dialysis requiring ARFs are becoming more common. Our data underscore the public health importance of ARF.

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.

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.

Patients with nephrotic syndrome (NS) are believed to be at increased risk of atherosclerosis and coronary heart disease (CHD), although existing evidence for this association has not been persuasive. The risk of CHD among 142 persons with NS documented by protein-uria > or = 3.5 g daily was compared with that among 142 matched controls randomly selected from the membership of a large Northern California health plan. Controls were matched for sex, year of birth, and presence in the health plan when the referent case was diagnosed. No diabetics were included in this study. Mean follow-up for nonfatal CHD events was 5.6 years for NS subjects and 11.2 years for controls. Among the NS subjects myocardial infarction (MI) developed in 11, and there were 58 deaths, seven because of CHD. Among the controls, there were four MIs and 10 deaths, three because of CHD. In matched-pair analysis, there were 11 MIs among NS subjects and none among controls [P = 0.001, lower bound of 95% confidence interval for relative risk (CI), 2.8]. In an unmatched analysis adjusted for hypertension and smoking at diagnosis of NS, the relative risk of MI was 5.5 (95% CI 1.6 to 18.3) and the relative risk of coronary death was 2.8 (95% CI 0.7 to 11.3). Omitting data of NS subjects with minimal change disease and systemic lupus erythematosus yielded similar results. These data suggest that persons with NS are at increased risk of CHD.

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 persistent glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 by the CKD-EPI equation) enrolled in Kaiser Permanente Northern California who were identified between 2002–2010 and who did not have prior ESRD or previously documented AF. Incident AF was identified using primary hospital discharge diagnoses and/or two 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) compared 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 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.

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