Hypertensive kidney disease (HKD) is believed to be a cause of end-stage renal disease (ESRD) in a significant number of patients living in America. Hypertensive nephrosclerosis or HKD is a vague diagnosis used especially when a patient does not have diabetes, is non-nephrotic, has no renal biopsy and is noted to have irreversible advanced chronic kidney disease (CKD) in the setting of radiologic changes and elevated blood pressures.
The Centers for Disease Control and Prevention estimates that 15% of US adults – 37 million people – have CKD. Data from the American College of Cardiology/American Heart Association (ACC/AHA) estimate that 45% of U.S. adults have hypertension (HTN), which is about 108 million people. Out of this population with HTN, about 45% have uncontrolled BP (140/90 mmHg or higher); this includes about 37 million U.S. adults.
Given that the CDC indicates that 1 in 5 adults with HTN may have CKD, one wonders which came first: the HTN or the CKD? As a provider, paying close attention to this when managing a patient can help contribute toward effectively reducing the incidence of ESRD attributable to HTN.
The Kidney Disease Quality Outcome Initiative (K/DOQI) defines CKD as kidney damage or glomerular filtration rate (GFR) <60ml/min/1.73m2Â for 3 months or more, irrespective of cause.
Guidelines on HTN from the ACC/AHA, 2017 defined hypertension as blood pressure at or above 130/80 mmHg. Stage 1 is defined as systolic blood pressure (SBP) 130-139 mmHg or diastolic blood pressure (DBP) 80-89mmHg. Stage 2 is defined as SBP >140 mmHg or DBP >90mm Hg.2,7
Consider a typical day in the life of a 60-year-old male patient who presents for his medical check-up, and further evaluation reveals a history of HTN for an unknown duration – perhaps three years. Upon conducting a thorough history, it is noted that an incidental diagnosis was made that resulted in putting the patient on one or two anti-hypertensive medications.
After further evaluation of the patient’s laboratory findings, he is referred to the renal clinic due to poor renal function, as depicted by his estimated glomerular filtration rate (eGFR) of 42 mL/min/1.73 m2 Patient denies any acute symptoms but acknowledges a history of cigarette smoking from years ago and mentions he has an appointment with his urologist to follow up on his prostatic disease. (See Figure 1 for the common pathophysiology of HTN leading to CKD/ESRD.)
Genetic predisposition to HTN, especially around variations in genes involved in the renin-angiotensin-aldosterone system, has been described and HTN has been shown to run in families. Inheritance patterns remain unclear. Using blood pressure data systematically acquired across three generations of the Framingham Heart Study, the authors showed that higher blood pressure, not only in parents but also in grandparents, is associated with risk of the same condition in third-generation individuals.1
Genetic association of HTN resulting in excess risk of ESRD in African-American individuals has been attributed to an MYH9 risk haplotype and suggests that hypertension may cause progressive kidney disease only in genetically susceptible individuals.1,9
There are also environmental factors complicating the occurrence of HTN, specifically lifestyle behaviors such as alcohol consumption and smoking, poor diet (high salt intake) and level of physical activity with obesity being of significant importance. Risk factors for HTN include a personal history of cardiovascular disease, diabetes, dyslipidemia, chronic kidney disease and a history of depression.
Blood pressure control can be impacted by problems such as denial and lack of adherence to medical care, especially in underserved populations, contributing to sustained hypertension, masked hypertension or white coat hypertension. Masked, uncontrolled HTN (MUCH) represents normotension in the doctor’s office while having elevated 24-hour ambulatory blood pressure. Confirmation of MUCH diagnosis should rely on ambulatory BP monitoring.2 On the other hand, white coat hypertension describes elevated blood pressure in the clinic but normal 24-hour ambulatory blood pressure, whereas sustained high blood pressure is elevated blood pressure in the clinic and elevated 24-hour ambulatory blood pressure.
Sustained hypertension, white-coat hypertension (found in 10-20% of CKD patients) and masked hypertension (found in 10-30% of CKD patients) have all been associated with an increased risk of death; the strongest association was found with masked hypertension. Among people with hypertension, the loss of the normal fall in night-time BP, called nondipping, diagnosed best by ambulatory BP monitoring (ABPM), is a risk factor for cardiovascular events and can be seen in as many as 80% of people with CKD. Both nocturnal hypertension and nondipping status have also been associated with a higher risk for adverse CV outcomes, as well as CKD progression.
Conversely, multiple approaches to possible mechanisms of hypertension in chronic kidney disease have evolved over the years. (See Figure 2.)
It can be inferred that kidney disease can be a cause and consequence of hypertension. It is clear that CKD from any source will be aggravated leading to ESRD if concurrent HTN is left uncontrolled. We assess CKD routinely starting with simple renal function parameters (serum creatinine and eGFR) together with investigation for albuminuria (dipstick or urinary albumin creatinine ratio [UACR] in early morning spot urine).3Â Further assessments will be useful if indicators of other secondary causes of hypertension exist.
HTN management begins with lifestyle modifications and pharmacotherapy often starting with an ACE inhibitor, angiotensin-receptor blocker, calcium-channel blocker or thiazide diuretic. In general, ACE inhibitors and ARBs are preferred first-line agents in patients with albuminuria or proteinuria, and diuretics may be useful in combination with ACE inhibitors or ARBs to balance the risk for hyperkalemia and enhance albuminuria or proteinuria reduction. In the absence of albuminuria or proteinuria, the optimal first-line agent for patients with CKD is debated and may be selected based on concurrent indications, including prostatic disease, cause of hypertension, need to treat hyperkalemia or fluid overload.
More recently, a new class of antihyperglycemic medications, the SGLT2 inhibitors, has been shown to be effective in reducing risk for adverse CV and kidney disease outcomes. SGLT2 inhibitors also possess antihypertensive effects that do not appear to be related to glucosuria.4
The Sprint randomized trial indicated that although lower rates of cardiovascular events associated with intensive treatment could result in improved health status, serious adverse events associated with low end-organ perfusion, including symptomatic hypotension, syncope and acute kidney injury, were more common among trial participants who were randomly assigned to intensive hypertension treatment.5, 8 In the Sprint study, which included 28% patients with CKD, treating HTN to a lower target goal of 120mmHg demonstrated no difference in the main kidney outcomes – onset of end-stage renal disease or a 50% decline in glomerular filtration rate.
The African-American Study of Kidney Disease and Hypertension (AASK) evaluated the effects of an intensive blood-pressure target, as compared with a traditional blood-pressure target, on the progression of chronic kidney disease among Black patients with hypertensive chronic kidney disease and showed no effect of blood-pressure control on kidney disease progression.6
Chronic kidney disease and HTN are intertwined in their pathophysiology and are often closely occurring, making it difficult to delineate cause and effect. It becomes important that the healthcare professional screen for one when the other is present and continuously focus on HTN control for patients with CKD to a goal of <130/80 mmHg as recommended by the ACC/AHA guidelines, given the cardiovascular benefits or, perhaps, deterrent effect of end-stage renal disease requiring renal replacement therapy.
References
1. Riyaz S. Patel1, Stefano Masi, and Stefano Taddei; Understanding the role of genetics in hypertension. European Heart Journal(2017)38, 2309–2312.doi:10.1093/eurheartj/ehx273
2. Rajiv Agarwal, Maria K. Pappas and Arjun D. Sinha, Masked Uncontrolled Hypertension in CKD.JASN March 2016,27(3)924-932;DOI:Â https://doi.org/10.1681/ASN.2015030243
3. Thomas Unger, Claudio Borghi, Fadi Charchar, Nadia A. Khan, et al. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension Vol. 75, Issue 6,June 2020;Pages1334-1357Â https://doi.org/10.1161/HypertensionAHA.120.15026
4. Elaine Ku, Benjamin J. Lee, Jenny Wei, and Matthew R. Weir. Hypertension in CKD: Core Curriculum 2019 Am J Kidney Dis. 74(1): 120-131. Published online March 19, 2019. doi: 10.1053/ j.ajkd.2018.12.044
5. The SPRINT Research Group. A randomized trial of intensive versus standard blood pressure control. N Engl J Med 2015;373:2103-2116
6. Lawrence J. Appel, Jackson T. Wright, Tom Greene, et al.Intensive Blood-Pressure Control in Hypertensive Chronic Kidney Disease.N Engl J Med Sep 2, 2010.; 363:918-929.DOI: 10.1056/NEJMoa0910975
7. Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults Hypertension. 2018;71(19):e13–115.
8. Glenn M. Chertow, Srinivasan Beddhu, Julia B. Lewis, Robert D. Toto and Alfred K. Cheung, Managing Hypertension in Patients with CKD: A Marathon, Not a SPRINT JASN January 2016, 27 (1) 40-43; DOI:Â https://doi.org/10.1681/ASN.2015101125
9. Hypertension-Associated Kidney Disease: Perhaps no More. Barry I. Freedman and John R. Sedor; JASN November 2008, 19 (11) 2047-2051; DOI:Â https://doi.org/10.1681/ASN.2008060621
10. Manuel T. Velasquez : Management of Hypertension in Chronic Kidney Disease. Chronic Renal Disease 2015, Pages 634-645.ScienceDirect https://doi.org/10.1016/B978-0-12-411602-3.00052-4
