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      Evaluating the Contribution of the Cause of Kidney Disease to Prognosis in CKD: Results From the Study of Heart and Renal Protection (SHARP)

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          Abstract

          Background

          The relevance of the cause of kidney disease to prognosis among patients with chronic kidney disease is uncertain.

          Study Design

          Observational study.

          Settings & Participants

          6,245 nondialysis participants in the Study of Heart and Renal Protection (SHARP).

          Predictor

          Baseline cause of kidney disease was categorized into 4 groups: cystic kidney disease, diabetic nephropathy, glomerulonephritis, and other recorded diagnoses.

          Outcomes

          End-stage renal disease (ESRD; dialysis or transplantation) and death.

          Results

          During an average 4.7 years' follow-up, 2,080 participants progressed to ESRD, including 454 with cystic kidney disease (23% per year), 378 with glomerulonephritis (10% per year), 309 with diabetic nephropathy (12% per year), and 939 with other recorded diagnoses (8% per year). By comparison with patients with cystic kidney disease, other disease groups had substantially lower adjusted risks of ESRD (relative risks of 0.28 [95% CI, 0.24-0.32], 0.40 [95% CI, 0.34-0.47], and 0.29 [95% CI, 0.25-0.32] for glomerulonephritis, diabetic nephropathy, and other recorded diagnoses, respectively). Albuminuria and baseline estimated glomerular filtration rate were associated more weakly with risk of ESRD in patients with cystic kidney disease than the 3 other diagnostic categories ( P for interaction, <0.001 and 0.01, respectively). Death before ESRD was uncommon in patients with cystic kidney disease, but was a major competing risk for participants with diabetic nephropathy, whose adjusted risk of death was 2-fold higher than that of the cystic kidney disease group (relative risk, 2.35 [95% CI, 1.73-3.18]).

          Limitations

          Exclusion of patients with prior myocardial infarction or coronary revascularization.

          Conclusions

          The cause of kidney disease has substantial prognostic implications. Other things being equal, patients with cystic kidney disease are at much higher risk of ESRD (and much lower risk of death before ESRD) than other patients. Patients with diabetic nephropathy are at particularly high risk of death prior to reaching ESRD.

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          Relation between kidney function, proteinuria, and adverse outcomes.

          Brenda R. Hemmelgarn, Braden J. Manns, Anita Lloyd … (2010)
          The current staging system for chronic kidney disease is based primarily on estimated glomerular filtration rate (eGFR) with lower eGFR associated with higher risk of adverse outcomes. Although proteinuria is also associated with adverse outcomes, it is not used to refine risk estimates of adverse events in this current system. To determine the association between reduced GFR, proteinuria, and adverse clinical outcomes. Community-based cohort study with participants identified from a province-wide laboratory registry that includes eGFR and proteinuria measurements from Alberta, Canada, between 2002 and 2007. There were 920 985 adults who had at least 1 outpatient serum creatinine measurement and who did not require renal replacement treatment at baseline. Proteinuria was assessed by urine dipstick or albumin-creatinine ratio (ACR). All-cause mortality, myocardial infarction, and progression to kidney failure. The majority of individuals (89.1%) had an eGFR of 60 mL/min/1.73 m(2) or greater. Over median follow-up of 35 months (range, 0-59 months), 27 959 participants (3.0%) died. The fully adjusted rate of all-cause mortality was higher in study participants with lower eGFRs or heavier proteinuria. Adjusted mortality rates were more than 2-fold higher among individuals with heavy proteinuria measured by urine dipstick and eGFR of 60 mL/min/1.73 m(2) or greater, as compared with those with eGFR of 45 to 59.9 mL/min/1.73 m(2) and normal protein excretion (rate, 7.2 [95% CI, 6.6-7.8] vs 2.9 [95% CI, 2.7-3.0] per 1000 person-years, respectively; rate ratio, 2.5 [95% CI, 2.3-2.7]). Similar results were observed when proteinuria was measured by ACR (15.9 [95% CI, 14.0-18.1] and 7.0 [95% CI, 6.4-7.6] per 1000 person-years for heavy and absent proteinuria, respectively; rate ratio, 2.3 [95% CI, 2.0-2.6]) and for the outcomes of hospitalization with acute myocardial infarction, end-stage renal disease, and doubling of serum creatinine level. The risks of mortality, myocardial infarction, and progression to kidney failure associated with a given level of eGFR are independently increased in patients with higher levels of proteinuria.
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            Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts.

            Ron T. Gansevoort, Kunihiro Matsushita, Marije van der Velde … (2011)
            Both a low estimated glomerular filtration rate (eGFR) and albuminuria are known risk factors for end-stage renal disease (ESRD). To determine their joint contribution to ESRD and other kidney outcomes, we performed a meta-analysis of nine general population cohorts with 845,125 participants and an additional eight cohorts with 173,892 patients, the latter selected because of their high risk for chronic kidney disease (CKD). In the general population, the risk for ESRD was unrelated to eGFR at values between 75 and 105 ml/min per 1.73 m(2) but increased exponentially at lower levels. Hazard ratios for eGFRs averaging 60, 45, and 15 were 4, 29, and 454, respectively, compared with an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log ESRD risk without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 30, 300, and 1000 mg/g were 5, 13, and 28, respectively, compared with an albumin-to-creatinine ratio of 5. Albuminuria and eGFR were associated with ESRD, without evidence for multiplicative interaction. Similar associations were found for acute kidney injury and progressive CKD. In high-risk cohorts, the findings were generally comparable. Thus, lower eGFR and higher albuminuria are risk factors for ESRD, acute kidney injury and progressive CKD in both general and high-risk populations, independent of each other and of cardiovascular risk factors.
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              Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study.

              Lawrence G Hunsicker, Sharon G. Adler, Arlene Caggiula … (1997)
              The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and strict blood pressure control on the decline in glomerular filtration rate (GFR) in 840 patients with diverse renal diseases. We describe a systematic analysis to determine baseline factors that predict the decline in GFR, or which alter the efficacy of the diet or blood pressure interventions. Univariate analysis identified 18 of 41 investigated baseline factors as significant (P < 0.05) predictors of GFR decline. In multivariate analysis, six factors--greater urine protein excretion, diagnosis of polycystic kidney disease (PKD), lower serum transferrin, higher mean arterial pressure, black race, and lower serum HDL cholesterol--independently predicted a faster decline in GFR. Together with the study interventions, these six factors accounted for 34.5% and 33.9% of the variance between patients in GFR slopes in Studies A and B, respectively, with proteinuria and PKD playing the predominant role. The mean rate of GFR decline was not significantly related to baseline GFR, suggesting an approximately linear mean GFR decline as renal disease progresses. The 41 baseline predictors were also assessed for their interactions with the diet and blood pressure interventions. A greater benefit of the low blood pressure intervention was found in patients with higher baseline urine protein. None of the 41 baseline factors were shown to predict a greater or lesser effect of dietary protein restriction.
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                Author and article information

                Contributors
                Martin J. Landray
                Journal
                Journal ID (nlm-ta): Am J Kidney Dis
                Journal ID (iso-abbrev): Am. J. Kidney Dis
                Title: American Journal of Kidney Diseases
                Publisher: W.B. Saunders
                ISSN (Print): 0272-6386
                ISSN (Electronic): 1523-6838
                Publication date PMC-release: 1 July 2014
                Publication date (Print): July 2014
                Volume: 64
                Issue: 1
                Pages: 40-48
                Affiliations
                [1 ]Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
                [2 ]North Bristol NHS Trust, Bristol, United Kingdom
                [3 ]National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
                [4 ]First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic
                [5 ]University of British Columbia, Vancouver, BC, Canada
                Author notes
                [∗ ]Address correspondence to Martin J. Landray, PhD, FRCP, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, United Kingdom. sharpclinical@ 123456ctsu.ox.ac.uk
                [∗]

                A list of the members of the SHARP Collaborative Group appears in the Acknowledgements.

                Article
                Publisher ID: S0272-6386(14)00025-0
                DOI: 10.1053/j.ajkd.2013.12.013
                PMC ID: 4068325
                PubMed ID: 24613056
                SO-VID: cb57c340-bbc1-46fa-beb0-a32dd46561be
                Copyright © © 2014 National Kidney Foundation, Inc. All rights reserved.
                History
                Date received : 13 September 2013
                Date accepted : 29 December 2013
                Categories
                Subject: Original Investigation
                Subject: Pathogenesis and Treatment of Kidney Disease

                ScienceOpen disciplines: Nephrology
                Keywords: kidney disease etiology,disease trajectory,end-stage renal disease (esrd),disease progression,prognosis,cystic kidney disease,risk factor
                Data availability:
                ScienceOpen disciplines: Nephrology
                Keywords: kidney disease etiology, disease trajectory, end-stage renal disease (esrd), disease progression, prognosis, cystic kidney disease, risk factor

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