Ronald D. Perrone

National Kidney Foundation Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification

Chronic kidney disease is a worldwide public health problem. In the United States, the incidence and prevalence of kidney failure are rising, the outcomes are poor, and the costs are high. The number of persons with kidney failure who are treated with dialysis and transplantation is projected to increase from 340 000 in 1999 to 651 000 in 2010 (1). The major outcomes of chronic kidney disease, regardless of cause, include progression to kidney failure, complications of decreased kidney function, and cardiovascular disease (CVD). Increasing evidence indicates that some of these adverse outcomes can be prevented or delayed by early detection and treatment (2). Unfortunately, chronic kidney disease is underdiagnosed and undertreated, resulting in lost opportunities for prevention (3-5), in part because of a lack of agreement on a definition and classification of stages in the progression of chronic kidney disease (6) and a lack of uniform application of simple tests for detection and evaluation. In February 2002, the Kidney Disease Outcomes Quality Initiative (K/DOQI) of the National Kidney Foundation (NKF) published 15 clinical practice guidelines on chronic kidney disease [7]. The goals of the guidelines are to 1) define chronic kidney disease and classify its stages, regardless of underlying cause; 2) evaluate laboratory measurements for the clinical assessment of kidney disease; 3) associate the level of kidney function with complications of chronic kidney disease; and 4) stratify the risk for loss of kidney function and development of CVD. Our goal is to disseminate the simple definition and five-stage classification system of chronic kidney disease, to summarize the major recommendations on early detection of chronic kidney disease in adults (Table 1), and to consider some of the issues associated with these recommendations. Because of the high prevalence of early stages of chronic kidney disease in the general population, this information is particularly important for general internists and specialists. Table 1. Guidelines, Recommendations, Ratings, and Key References Methods The guidelines of the K/DOQI are based on a systematic review of the literature. The approach used for the review was outlined by the Agency for Healthcare Research and Quality (formerly the Agency for Health Care Policy and Research) (46), with modifications appropriate to the available evidence and the goals of the K/DOQI Work Group. The Work Group considered diverse topics, which would have been too large for a comprehensive review of the literature. Instead, a selective review of published evidence was used to focus on specific questions: a summary of reviews for established concepts and a review of original articles and data for new concepts. The strength of recommendations is graded according to a new classification (Table 2) recently adopted by the K/DOQI Advisory Board (see Appendix 1). Table 2. National Kidney Foundation Kidney Disease Outcomes Quality Initiative Rating of the Strength of Recommendations Framework The Work Group defined two principal outcomes of chronic kidney disease: the progressive loss of kidney function over time (Figure 1) and the development and progression of CVD. Figure 1, which defines stages of chronic kidney disease, as well as antecedent conditions, outcomes, risk factors for adverse outcomes, and actions to improve outcomes, is a model of the course of chronic kidney disease. This diagram provides a framework that has previously been lacking for the development of a public health approach to chronic kidney disease. Figure 1. Evidence model for stages in the initiation and progression of chronic kidney disease ( CKD ) and therapeutic interventions. black dark gray light gray white GFR Table 3. Risk Factors for Chronic Kidney Disease and Its Outcomes Risk factors for chronic kidney disease are defined as attributes associated with increased risk for adverse outcomes of chronic kidney disease (Table 3). The guidelines focus primarily on identifying susceptibility factors and initiation factors (to define persons at increased risk for developing chronic kidney disease) and progression factors (to define persons at high risk for worsening kidney damage and subsequent loss of kidney function). Because kidney disease usually begins late in life and progresses slowly, most persons in the stage of decreased glomerular filtration rate (GFR) die of CVD before they develop kidney failure. However, decreased GFR is associated with a wide range of complications, such as hypertension, anemia, malnutrition, bone disease, neuropathy, and decreased quality of life, which can be prevented or ameliorated by treatment at earlier stages. Treatment can also slow the progression to kidney failure. Thus, measures to prevent, detect, and treat chronic kidney disease in its earlier stages could reduce the adverse outcomes of chronic kidney disease. Cardiovascular disease deserves special consideration as a complication of chronic kidney disease because 1) CVD events are more common than kidney failure in patients with chronic kidney disease, 2) chronic kidney disease seems to be a risk factor for CVD, and 3) CVD in patients with chronic kidney disease is treatable and potentially preventable (48-50). The 1998 Report of the NKF Task Force on Cardiovascular Disease in Chronic Renal Disease recommended that patients with chronic kidney disease be considered in the highest risk group for subsequent CVD events and that most interventions that are effective in the general population should also be applied to patients with chronic kidney disease (49). Definition and Classification of Stages of Chronic Kidney Disease Guideline 1. Definition and Stages of Chronic Kidney Disease Adverse outcomes can often be prevented or delayed through early detection and treatment of chronic kidney disease. Earlier stages of chronic kidney disease can be detected through routine laboratory measurements. Chronic kidney disease is defined as either kidney damage or decreased kidney function (decreased GFR) for 3 or more months (level A recommendation). Kidney disease can be diagnosed without knowledge of its cause. Kidney damage is usually ascertained by markers rather than by kidney biopsy. According to the Work Group, persistent proteinuria is the principal marker of kidney damage (8, 9). An albumincreatinine ratio greater than 30 mg/g in untimed (spot) urine samples is usually considered abnormal; proposed sex-specific cut points are greater than 17 mg/g in men and greater than 25 mg/g in women (10, 11). Other markers of damage include abnormalities in urine sediment, abnormalities in blood and urine chemistry measurements, and abnormal findings on imaging studies. Persons with normal GFR but with markers of kidney damage are at increased risk for adverse outcomes of chronic kidney disease. Glomerular filtration rate is the best measure of overall kidney function in health and disease (12). The normal level of GFR varies according to age, sex, and body size. Normal GFR in young adults is approximately 120 to 130 mL/min per 1.73 m2 and declines with age (12-15). A GFR level less than 60 mL/min per 1.73 m2 represents loss of half or more of the adult level of normal kidney function. Below this level, the prevalence of complications of chronic kidney disease increases. Although the age-related decline in GFR has been considered part of normal aging, decreased GFR in the elderly is an independent predictor of adverse outcomes, such as death and CVD (51-53). In addition, decreased GFR in the elderly requires adjustment in drug dosages, as in other patients with chronic kidney disease (54). Therefore, the definition of chronic kidney disease is the same, regardless of age. Because GFR declines with age, the prevalence of chronic kidney disease increases with age; approximately 17% of persons older than 60 years of age have an estimated GFR less than 60 mL/min per 1.73 m2 (16). The guidelines define kidney failure as either 1) GFR less than 15 mL/min per 1.73 m2, which is accompanied in most cases by signs and symptoms of uremia, or 2) a need to start kidney replacement therapy (dialysis or transplantation). Approximately 98% of patients with kidney failure in the United States begin dialysis when their GFR is less than 15 mL/min per 1.73 m2 (17). Kidney failure is not synonymous with end-stage renal disease (ESRD). End-stage renal disease is an administrative term in the United States. It indicates that a patient is treated with dialysis or transplantation, which is the condition for payment for health care by the Medicare ESRD Program. The classification of ESRD does not include patients with kidney failure who are not treated with dialysis and transplantation. Thus, although the term ESRD provides a simple operational classification of patients according to treatment, it does not precisely define a specific level of kidney function. The level of kidney function, regardless of diagnosis, determines the stage of chronic kidney disease according to the K/DOQI chronic kidney disease classification (level A recommendation). Data from the Third National Health and Nutrition Examination Survey (NHANES III) show the increasing prevalence of complications of chronic kidney disease at lower levels of GFR (7). These data and other studies provide a strong basis for using GFR to classify the stage of severity of chronic kidney disease. Table 4 shows the classification of stages of chronic kidney disease and the prevalence of each stage, estimated by using data from NHANES III (16). Approximately 11% of the U.S. adult population (20 million persons from 1988 to 1994) have chronic kidney disease. The prevalence of early stages of disease (stages 1 to 4; 10.8%) is more than 100 times greater than the prevalence of kidney failure (stage 5; 0.1%). The burden of illness associated with earlier stages of chronic kidney disease has not been systematically studied (55,

Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease

BACKGROUND The course of autosomal dominant polycystic kidney disease (ADPKD) is often associated with pain, hypertension, and kidney failure. Preclinical studies indicated that vasopressin V(2)-receptor antagonists inhibit cyst growth and slow the decline of kidney function. METHODS In this phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, we randomly assigned 1445 patients, 18 to 50 years of age, who had ADPKD with a total kidney volume of 750 ml or more and an estimated creatinine clearance of 60 ml per minute or more, in a 2:1 ratio to receive tolvaptan, a V(2)-receptor antagonist, at the highest of three twice-daily dose regimens that the patient found tolerable, or placebo. The primary outcome was the annual rate of change in the total kidney volume. Sequential secondary end points included a composite of time to clinical progression (defined as worsening kidney function, kidney pain, hypertension, and albuminuria) and rate of kidney-function decline. RESULTS Over a 3-year period, the increase in total kidney volume in the tolvaptan group was 2.8% per year (95% confidence interval [CI], 2.5 to 3.1), versus 5.5% per year in the placebo group (95% CI, 5.1 to 6.0; P<0.001). The composite end point favored tolvaptan over placebo (44 vs. 50 events per 100 follow-up-years, P=0.01), with lower rates of worsening kidney function (2 vs. 5 events per 100 person-years of follow-up, P<0.001) and kidney pain (5 vs. 7 events per 100 person-years of follow-up, P=0.007). Tolvaptan was associated with a slower decline in kidney function (reciprocal of the serum creatinine level, -2.61 [mg per milliliter](-1) per year vs. -3.81 [mg per milliliter](-1) per year; P<0.001). There were fewer ADPKD-related adverse events in the tolvaptan group but more events related to aquaresis (excretion of electrolyte-free water) and hepatic adverse events unrelated to ADPKD, contributing to a higher discontinuation rate (23%, vs. 14% in the placebo group). CONCLUSIONS Tolvaptan, as compared with placebo, slowed the increase in total kidney volume and the decline in kidney function over a 3-year period in patients with ADPKD but was associated with a higher discontinuation rate, owing to adverse events. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; TEMPO 3:4 ClinicalTrials.gov number, NCT00428948.).

Utility of Radioisotopic Filtration Markers in Chronic Renal Issufficiency: Simultaneous Comparison of 125I-Iothalamate, 169Yb-DTPA, 99mTc-DTPA, and Inulin

Assessment of glomerular filtration rate (GFR) with inulin is cumbersome and time-consuming. Radioisotopic filtration markers have been studied as filtration markers because they can be used without continuous intravenous (IV) infusion and because analysis is relatively simple. Although the clearances of 99m Tc-diethylenetriaminepentaacetic acid (DTPA), 169 Yb-DTPA, and 125 1-iothalamate have each been compared with inulin, rarely has the comparability of radioisotopic filtration markers been directly evaluated in the same subject. To this purpose, we determined the renal clearance of inulin administered by continuous infusion and the above radioisotopic filtration markers administered as bolus injections, simultaneously in four subjects with normal renal function and 16 subjects with renal insufficiency. Subjects were studied twice in order to assess within-study and between-study variability. Unlabeled iothalamate was infused during the second half of each study to assess its effect on clearances. We found that renal clearance of 1251-iothalamate and 169Yb-DTPA significantly exceeded clearance of inulin in patients with renal insufficiency, but only by several mL·min -1 ·1.73 m -2 . Overestimation of inulin clearance by radioisotopic filtration markers was found in all normal subjects. No differences between markers were found in the coefficient of variation of clearances either between periods on a given study day (within-day variability) or between the two study days (between-day variability). The true test variability between days did not correlate with within-test variability. We conclude that the renal clearance of 99m Tc-DTPA, 169 Yb-DTPA, or 125 I-iothalamate administered as a single IV or subcutaneous injection can be used to accurately measure GFR in subjects with renal insufficiency; use of the single injection technique may overestimate GFR in normal subjects.

Blood Pressure in Early Autosomal Dominant Polycystic Kidney Disease

BACKGROUND Hypertension is common in autosomal dominant polycystic kidney disease (ADPKD) and is associated with increased total kidney volume, activation of the renin-angiotensin-aldosterone system, and progression of kidney disease. METHODS In this double-blind, placebo-controlled trial, we randomly assigned 558 hypertensive participants with ADPKD (15 to 49 years of age, with an estimated glomerular filtration rate [GFR] >60 ml per minute per 1.73 m(2) of body-surface area) to either a standard blood-pressure target (120/70 to 130/80 mm Hg) or a low blood-pressure target (95/60 to 110/75 mm Hg) and to either an angiotensin-converting-enzyme inhibitor (lisinopril) plus an angiotensin-receptor blocker (telmisartan) or lisinopril plus placebo. The primary outcome was the annual percentage change in the total kidney volume. RESULTS The annual percentage increase in total kidney volume was significantly lower in the low-blood-pressure group than in the standard-blood-pressure group (5.6% vs. 6.6%, P=0.006), without significant differences between the lisinopril-telmisartan group and the lisinopril-placebo group. The rate of change in estimated GFR was similar in the two medication groups, with a negative slope difference in the short term in the low-blood-pressure group as compared with the standard-blood-pressure group (P<0.001) and a marginally positive slope difference in the long term (P=0.05). The left-ventricular-mass index decreased more in the low-blood-pressure group than in the standard-blood-pressure group (-1.17 vs. -0.57 g per square meter per year, P<0.001); urinary albumin excretion was reduced by 3.77% with the low-pressure target and increased by 2.43% with the standard target (P<0.001). Dizziness and light-headedness were more common in the low-blood-pressure group than in the standard-blood-pressure group (80.7% vs. 69.4%, P=0.002). CONCLUSIONS In early ADPKD, the combination of lisinopril and telmisartan did not significantly alter the rate of increase in total kidney volume. As compared with standard blood-pressure control, rigorous blood-pressure control was associated with a slower increase in total kidney volume, no overall change in the estimated GFR, a greater decline in the left-ventricular-mass index, and greater reduction in urinary albumin excretion. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; HALT-PKD [Study A] ClinicalTrials.gov number, NCT00283686.).

Autosomal Dominant Polycystic Kidney Disease (ADPKD): Executive Summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Autosomal-dominant polycystic kidney disease (ADPKD) affects up to 12 million individuals and is the fourth most common cause for renal replacement therapy worldwide. There have been many recent advances in the understanding of its molecular genetics and biology, and in the diagnosis and management of its manifestations. Yet, diagnosis, evaluation, prevention, and treatment vary widely and there are no broadly accepted practice guidelines. Barriers to translation of basic science breakthroughs to clinical care exist, with considerable heterogeneity across countries. The Kidney Disease: Improving Global Outcomes Controversies Conference on ADPKD brought together a panel of multidisciplinary clinical expertise and engaged patients to identify areas of consensus, gaps in knowledge, and research and health-care priorities related to diagnosis; monitoring of kidney disease progression; management of hypertension, renal function decline and complications; end-stage renal disease; extrarenal complications; and practical integrated patient support. These are summarized in this review.

The HALT Polycystic Kidney Disease Trials: Design and Implementation

BACKGROUND AND OBJECTIVES Two HALT PKD trials will investigate interventions that potentially slow kidney disease progression in hypertensive autosomal dominant polycystic kidney disease (ADPKD) patients. Studies were designed in early and later stages of ADPKD to assess the impact of intensive blockade of the renin-angiotensin-aldosterone system and level of BP control on progressive renal disease. Design, settings, participants, and measurements: PKD-HALT trials are multicenter, randomized, double-blind, placebo-controlled trials studying 1018 hypertensive ADPKD patients enrolled over 3 yr with 4 to 8 yr of follow-up. In study A, 548 participants, estimated GFR (eGFR) of >60 ml/min per 1.73 m(2) were randomized to one of four arms in a 2-by-2 design: combination angiotensin converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) therapy versus ACEi monotherapy at two levels of BP control. In study B, 470 participants, eGFR of 25 to 60 ml/min per 1.73 m2 compared ACEi/ARB therapy versus ACEi monotherapy, with BP control of 120 to 130/70 to 80 mmHg. Primary outcomes of studies A and B are MR-based percent change kidney volume and a composite endpoint of time to 50% reduction of baseline estimated eGFR, ESRD, or death, respectively. RESULTS This report describes design issues related to (1) novel endpoints such as kidney volume, (2) home versus office BP measures, and (3) the impact of RAAS inhibition on kidney and patient outcomes, safety, and quality of life. CONCLUSIONS HALT PKD will evaluate potential benefits of rigorous BP control and inhibition of the renin-angiotensin-aldosterone system on kidney disease progression in ADPKD.

Angiotensin Blockade in Late Autosomal Dominant Polycystic Kidney Disease

BACKGROUND Hypertension develops early in patients with autosomal dominant polycystic kidney disease (ADPKD) and is associated with disease progression. The renin-angiotensin-aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in patients with ADPKD. Dual blockade of the RAAS may circumvent compensatory mechanisms that limit the efficacy of monotherapy with an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin II-receptor blocker (ARB). METHODS In this double-blind, placebo-controlled trial, we randomly assigned 486 patients, 18 to 64 years of age, with ADPKD (estimated glomerular filtration rate [GFR], 25 to 60 ml per minute per 1.73 m(2) of body-surface area) to receive an ACE inhibitor (lisinopril) and placebo or lisinopril and an ARB (telmisartan), with the doses adjusted to achieve a blood pressure of 110/70 to 130/80 mm Hg. The composite primary outcome was the time to death, end-stage renal disease, or a 50% reduction from the baseline estimated GFR. Secondary outcomes included the rates of change in urinary aldosterone and albumin excretion, frequency of hospitalizations for any cause and for cardiovascular causes, incidence of pain, frequency of ADPKD-related symptoms, quality of life, and adverse study-medication effects. Patients were followed for 5 to 8 years. RESULTS There was no significant difference between the study groups in the incidence of the composite primary outcome (hazard ratio with lisinopril-telmisartan, 1.08; 95% confidence interval, 0.82 to 1.42). The two treatments controlled blood pressure and lowered urinary aldosterone excretion similarly. The rates of decline in the estimated GFR, urinary albumin excretion, and other secondary outcomes and adverse events, including hyperkalemia and acute kidney injury, were also similar in the two groups. CONCLUSIONS Monotherapy with an ACE inhibitor was associated with blood-pressure control in most patients with ADPKD and stage 3 chronic kidney disease. The addition of an ARB did not alter the decline in the estimated GFR. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; HALT-PKD [Study B] ClinicalTrials.gov number, NCT01885559.).

Rationale and design of the TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and its Outcomes) 3-4 Study.

BACKGROUND Current management of autosomal dominant polycystic kidney disease (ADPKD) is focused on treating disease complications, not on slowing cyst development or preventing progression to kidney failure. Tolvaptan, a selective vasopressin V2 (vasopressin 2) receptor antagonist, has been proved to inhibit kidney cyst growth and preserve kidney function in multiple animal models of polycystic kidney disease. The TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) 3-4 Study will examine the long-term effectiveness and safety of tolvaptan in patients with ADPKD. We report baseline characteristics and revised power calculations for the trial. STUDY DESIGN A prospective, 3-year, multicenter, double-blind, placebo-controlled trial of tolvaptan, a selective V2 receptor antagonist. Primary outcome is total kidney volume percentage of change from baseline for tolvaptan relative to placebo. Secondary outcome parameters include time to ADPKD-associated complications (kidney function decrease, blood pressure control, renal pain, and albuminuria) and safety end points. SETTING & PARTICIPANTS This trial includes patients with ADPKD with relatively preserved kidney function (baseline estimated creatinine clearance ≥60 mL/min), aged 50 years or younger, and with total kidney volume measured using magnetic resonance imaging ≥750 mL. INTERVENTION Administration of placebo or tolvaptan, dose titrated to tolerance. OUTCOMES Number of subjects enrolled and baseline characteristics. MEASUREMENTS Total kidney volume, kidney function, albuminuria, kidney pain, and vital signs. RESULTS 1,445 patients with ADPKD were enrolled between March 2007 and January 2009. Preliminary baseline median total kidney volume was 1.46 L, and estimated creatinine clearance was 105 ± 34 mL/min. A prespecified blinded sample-size recalculation at two-thirds enrollment confirmed the likely power of the study to detect 20% differences from placebo in the primary and key secondary end points at P < 0.05. LIMITATIONS This is a preselected ADPKD population chosen for its risk of progression to kidney failure and may not represent the general ADPKD population. If study results are positive with regard to the primary end point, positive effects on other secondary clinical outcomes will be required to assess overall benefit. CONCLUSIONS This randomized trial is the largest clinical study of a proposed ADPKD intervention to date. It targets patients with ADPKD with early disease who are projected to have rapid cyst growth and accelerated outcomes. Blockade of vasopressin V2 receptor is hypothesized to inhibit cyst growth, thereby delaying additional adverse clinical outcomes.

Inflammation, Oxidative Stress, and Insulin Resistance in Polycystic Kidney Disease

BACKGROUND AND OBJECTIVES Most deaths in autosomal dominant polycystic kidney disease (ADPKD) are attributable to cardiovascular disease (CVD). We examined novel CVD biomarkers in different stages of ADPKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We recruited 50 hypertensive subjects with ADPKD with estimated GFR (eGFR) of >60 ml/min per 1.73 m(2); 52 hypertensive subjects with ADPKD with eGFR of 25 to 60 ml/min per 1.73 m(2); 42 normotensive subjects with ADPKD and eGFR of >60 ml/min per 1.73 m(2); and 50 healthy controls. We assayed serum C-reactive protein and IL-6 as markers of inflammation; plasma 8-epi-prostaglandin F(2α (8-epi-PGF2α)) and superoxide dismutase (SOD) as markers of oxidative stress; and homeostasis model assessment (HOMA) as a measure of insulin resistance. RESULTS The hypertensive ADPKD eGFR of 25 to 60 group had higher levels of C-reactive protein and IL-6 than controls, normotensive ADPKD with eGFR of >60, and hypertensive ADPKD with eGFR of >60. The normotensive ADPKD eGFR >60, hypertensive ADPKD eGFR >60, and hypertensive ADPKD eGFR 25 to 60 groups had higher 8-epi-PGF(2α) and lower SOD than controls, with no difference between the ADPKD groups. There was no difference in HOMA levels between any of the groups. Adjustment for age, race, gender, and body mass index did not alter these relationships. CONCLUSIONS Inflammation and oxidative stress are evident early in ADPKD even with preserved kidney function. Inflammation exhibits a graded relationship with levels of kidney function, whereas oxidative stress demonstrates a threshold effect. These pathways may be therapeutic targets for CVD risk mitigation.

Performance of Creatinine-Based GFR Estimating Equations in Solid-Organ Transplant Recipients

BACKGROUND Accurate assessment of kidney function is important for the management of solid-organ transplant recipients. In other clinical populations, glomerular filtration rate (GFR) most commonly is estimated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine or the 4-variable MDRD (Modification of Diet in Renal Disease) Study equation. The accuracy of these equations compared with other GFR estimating equations in transplant recipients has not been carefully studied. STUDY DESIGN Diagnostic test study. SETTING & PARTICIPANTS Solid-organ transplant recipients longer than 6 months posttransplantation from 5 clinical populations (N=3,622, including recipients of kidney [53%], liver [35%], and other or multiple organs [12%]). INDEX TEST Estimated GFR (eGFR) using creatinine-based GFR estimating equations identified from a systematic review of the literature. Performance of the CKD-EPI creatinine and the MDRD Study equations was compared with alternative equations. REFERENCE TEST Measured GFR (mGFR) from urinary clearance of iothalamate or plasma clearance of iohexol. MEASUREMENTS Error (difference between mGFR and eGFR) expressed as P30 (proportion of absolute percent error <30%) and mean absolute error. RESULTS We identified 26 GFR estimating equations. Mean mGFR was 55.1±22.7 (SD) mL/min/1.73 m(2). P30 and mean absolute error for the CKD-EPI and the MDRD Study equations were 78.9% (99.6% CI, 76.9%-80.8%) for both and 10.6 (99.6% CI, 10.1-11.1) versus 11.0 (99.6% CI, 10.5-11.5) mL/min/1.73 m(2), respectively; these equations were more accurate than any of the alternative equations (P <0.001 for all pairwise comparisons for both measures). They performed better than or as well as the alternative equations in most subgroups defined by demographic and clinical characteristics, including type of transplanted organ. LIMITATIONS Study population included few nonwhites and people with solid-organ transplants other than liver and kidneys. CONCLUSIONS The CKD-EPI creatinine and the MDRD Study equations perform better than the alternative creatinine-based estimating equations in solid-organ transplant recipients. They can be used for clinical management.