Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts.

We studied here the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in individuals with chronic kidney disease (CKD). We performed a collaborative meta-analysis of 13 studies totaling 21,688 patients selected for CKD of diverse etiology. After adjustment for potential confounders and albuminuria, we found that a 15 ml/min per 1.73 m² lower eGFR below a threshold of 45 ml/min per 1.73 m² was significantly associated with mortality and ESRD (pooled hazard ratios (HRs) of 1.47 and 6.24, respectively). There was significant heterogeneity between studies for both HR estimates. After adjustment for risk factors and eGFR, an eightfold higher albumin- or protein-to-creatinine ratio was significantly associated with mortality (pooled HR 1.40) without evidence of significant heterogeneity and with ESRD (pooled HR 3.04), with significant heterogeneity between HR estimates. Lower eGFR and more severe albuminuria independently predict mortality and ESRD among individuals selected for CKD, with the associations stronger for ESRD than for mortality. Thus, these relationships are consistent with CKD stage classifications based on eGFR and suggest that albuminuria provides additional prognostic information among individuals with CKD.

Predicting the risk of hyperkalemia in patients with chronic kidney disease starting lisinopril.

PURPOSE: Angiotensin-converting enzyme (ACE) inhibitors are recommended for patients with chronic kidney disease (CKD) because they slow disease progression. But physicians' concerns about the risk of hyperkalemia (elevated serum potassium level), a potentially fatal adverse effect, may limit optimal management with ACE-inhibitors. We synthesized known predictors of hyperkalemia into a prognostic risk score to predict the risk of hyperkalemia. METHODS: We assembled a retrospective cohort of adult patients with possible CKD (at least one estimated glomerular filtration rate (eGFR) value less than 60 ml/min/1.73 m(2)) who started an ACE-inhibitor (i.e., incident users) between 1998 and 2006 at a health maintenance organization. We followed patients for hyperkalemia: (1) potassium value >5.5 mmol/L; or (2) diagnosis code for hyperkalemia. Cox regression synthesized a priori predictors recorded in the electronic medical record into a risk score. RESULTS: We followed 5171 patients and 145 experienced hyperkalemia, a 90-day risk of 2.8%. Predictors included: age, eGFR, diabetes, heart failure, potassium supplements, potassium-sparing diuretics, and a high dose for the ACE-inhibitor (lisinopril). The risk score separated high-risk patients (top quintile, observed risk of 6.9%) from low-risk patients (bottom quintile, observed risk of 0.7%). Predicted and observed risks agreed within 1% for each quintile. The risk increased gradually in relation to declining eGFR with no apparent threshold for contraindicating ACE-inhibitors. CONCLUSIONS: The risk score separated high-risk patients (who may need more intensive laboratory monitoring) from low-risk patients. The risk score should be validated in other populations before it is ready for use in clinical practice.

The aging kidney: physiological changes.

Age-associated loss of kidney function has been recognized for decades. With aging, many subjects exhibit progressive decreases in glomerular filtration rate and renal blood flow, with wide variability among individuals. The fall in glomerular filtration rate is because of reductions in the glomerular capillary plasma flow rate and the glomerular capillary ultrafiltration coefficient. In addition, a primary reduction in afferent arteriolar resistance is associated with an increase in glomerular capillary hydraulic pressure. These hemodynamic changes occur in concert with structural changes, including loss of renal mass; hyalinization of afferent arterioles and in some cases, development of aglomerular arterioles; an increase in the percentage of sclerotic glomeruli; and tubulointerstitial fibrosis. Aging is associated with altered activity and responsiveness to vasoactive stimuli, such that responses to vasoconstrictor stimuli are enhanced, whereas vasodilatory responses are impaired. Changes in the activity of the renin-angiotensin and nitric oxide systems appear to be particularly important, as is the modulating effect of gender. These changes may predispose the older kidney to acute kidney injury, including normotensive ischemic nephropathy, as well as progressive chronic kidney disease.