Primary prevention of chronic kidney disease: blood pressure targets Date written: July 2012 Author: Graeme Turner, Kate Wiggins, David Johnson

GUIDELINES a. We recommend that patients achieve standard BP targets < 140/90 as this reduces mortality and morbidity outcomes. (1A)

UNGRADED SUGGESTIONS FOR CLINICAL CARE Patients in Stages 1-2 CKD should have their blood pressure checked annually Patients in Stages 3A and 3B should have their blood pressure checked 3-6 monthly

IMPLEMENTATION AND AUDIT KCAT education programs for primary health care providers should incorporate the CARI Early CKD Lifestyle Modification recommendations. Primary health care practitioners should regularly audit their practices to ascertain the proportion of their hypertensive patient population that meets the KHA-CARI Early CKD Guideline BP targets for primary prevention of CKD and cardiovascular disease.

BACKGROUND Chronic kidney disease (CKD) is associated with considerable morbidity and increased mortality risk. Biochemical evidence of CKD (reduced estimated GFR, elevated serum creatinine) usually indicates the presence of tubulointerstitial fibrosis within the kidney. Such pathology is irreversible, therefore the aim of treatment in many patients with CKD is to delay progression of disease rather than achieve a cure. In light of this it is clear that implementation of primary prevention measures to avoid development of CKD is a preferable strategy. Whilst much information is available about risk factors for development of CKD (refer to Early CKD CARI Guideline subtopic 2) it is less clear whether risk factor modification prevents development of CKD. One such risk factor is high blood pressure, which evidence shows is associated with an increased incidence of CKD[1-6]. The aim of this guideline was to evaluate currently available clinical evidence of the benefits of treatment of elevated blood pressure in the primary prevention of CKD. In this guideline prevention of CKD is defined as a normal serum creatinine, eGFR above 60 mL/minute and absence of urinary albumin, protein or haematuria.

SEARCH STRATEGY Databases searched: Text words for chronic kidney disease were combined with MeSH terms and text words for high blood pressure. The search was carried out in Medline (1966 – August 2009). No language restrictions were placed on the search. The conference proceedings of the American Society of Nephrology from 1994-2008 were also searched for trials. A search update was conducted in Medline (2009 – May 2012) using the same MeSH terms and text words. Date of search/es: August 2009; May 2012 ________________________________________________________________________________________________________________________ Early Chronic Kidney Disease July 2012 Page 1 of 7

WHAT IS THE EVIDENCE? Blood Pressure in primary progression of kidney disease Two meta-analyses addressing blood pressure targets and the risk of developing kidney disease were identified. Arguedas et al. [7] looked at treatment blood pressure targets for hypertension. Current targets of >140-160/90-100 mmHg were historically set by professional consensus. They identified 7 RCT’s of which 5 reported the risk of developing end stage kidney disease. In these trials the incidence of end stage renal disease was similar between patients randomized to “lower” or “standard (>140160/90-100)” blood pressure targets. The meta-analysis by Hsu [8] of 10 RCT’s found that among patients with non-malignant hypertension treatment of patients with antihypertensive drug therapy did not lower the risk of renal dysfunction. Findings from epidemiological and observational studies are somewhat conflicting to the above 2 mentioned meta-analysis [7, 8]. Hsu et al. [9] reviewed the data for the 316,675 Kaiser Permanente participants without kidney disease at baseline. They showed an increased risk of kidney disease as blood pressure increased above 120/80 mm Hg with a RR of 1.63 at 120-129/80-84 mm Hg increasing to a RR of 4.25 at BP>210/120. Schaeffner et al. [10] prospectively followed the Physicians Health Study participants who did not have kidney disease at baseline. They also found an increasing odds ratio of kidney disease as blood pressure increased above 120/75 mm Hg. In the meta-analysis reviewed there were no negative outcomes reported in the lower target groups. Current evidence supports treatment of hypertension to traditional targets and further research is required to investigate the benefits of treating hypertension to lower targets in the primary prevention of kidney disease.

SUMMARY OF EVIDENCE Evidence regarding the role of blood pressure in the primary prevention of kidney disease suggests that treatment of hypertension is beneficial. Targets for treatment of hypertension should be traditional targets of less than 140-160/90-100 from a kidney perspective. Treatment of hypertension in established kidney disease is covered in a separate guideline and has lower blood pressure targets.

WHAT DO THE OTHER GUIDELINES SAY? Kidney Disease Outcomes Quality Initiative: [11] GUIDELINE 7. Association of Level of GFR with Hypertension (p.124) • Blood pressure should be closely monitored in all patients with chronic kidney disease. • Treatment of high blood pressure in chronic kidney disease should include specification of target blood pressure levels, non-pharmacologic therapy, and specific antihypertensive agents for the prevention of progression of kidney disease and development of cardiovascular disease (R) JNC-VI recommends a goal blood pressure of