Secondary Hypertension presentations.pptx

Briefing

1. Secondary Hypertension Presenter: Dr. Ermiyas Y.[IMR2] Moderator: Dr. Workagegnehu H.[Consultant Internist and Nephrologist]

2. Outline of Presentation Introduction Hypertension in CKD Renovascular hypertension Endocrine causes of hypertension Neurogenic hypertension References

3. Introduction Hypertension is one of the leading causes of the global burden of disease affects more than one billion individuals and causes an estimated 9.4 million deaths per year Hypertension doubles the risk of cardiovascular diseases, including coronary heart disease (CHD), congestive heart failure (CHF), ischemic and hemorrhagic stroke, renal failure, and peripheral arterial disease (PAD)

4. Secondary hy pertension An underlying disorder causing the elevation of blood pressure can be identified Accounts for 5–20% of hypertensive patients a more extensive evaluation should be done in patients who have clinical clues suggesting the possible presence of secondary hypertension Treatment of underlying disorder can lead to partial or complete cure from hypertension

5. Hypertension in CKD R enal disease is the most common cause of secondary hypertension Hypertension is present in >80% of patients with chronic renal failure P revalence increases further as the GFR falls Modification of Diet in Renal Disease Study showed prevalence of hypertension rose from 65 to 95 percent as the GFR fell from 85 to 15 mL/min per 1.73 m2 It may be difficult to determine whether hypertension or renal disease was the initial disorder

6. Factors contributing to the increased prevalence of HTN in CKD Sodium retention Increased activity of the renin-angiotensin system enhanced activity of the sympathetic nervous system Secondary hyperparathyroidism which raises the intracellular calcium concentration Treatment with erythropoietin may increase blood pressure Impaired nitric oxide synthesis and endothelium-mediated vasodilatation

7. Treatment of HTN in CKD Standardized blood pressure measurement Lifestyle interventions for lowering blood pressure Sodium intake- <2gm of sodium or <5gm of salt per day Physical activity- individualized Others: weight loss, reducing alcohol consumption , heart-healthy diet pattern Pharmacologic management of HTN

8. Lifestyle interventions BP Goal

9. Pharmacologic management of HTN

10. Renovascular Hypertension

11. Normal Renovascular anatomy In most individuals, kidney has a single RA with a lumen diameter of 3 to 7 mm . Multiple RAs can occur in about 31%, with bilateral supernumerary arteries in 11% Collaterals to the kidney can maintain renal parenchymal viability in the face of main RA occlusion Introduction

12. Intro… RVH is defined as a syndrome of elevated BP (systolic and/or diastolic) produced by any condition that leads to reduced perfusion of the kidneys is a potentially curable form of hypertension occurs in less than 1 % of patients with mild hypertension may be as high as 10 to 40 % in patients with acute, severe, or refractory hypertension

13. Intro… The most common cause of RVH is RA stenosis RA fibromuscular dysplasia (FMD ) and atherosclerotic disease are the two most common causes of RVH Other common causes include: Takayasu arteritis (TA), aortic coarctation

14. Pathogenesis Central to the pathogenesis of RVH is activation of the RAAS with release of renin from the juxtaglomerular apparatus In the absence of RAAS blockade, systemic arterial pressures increase until renal perfusion is restored A fall in renal perfusion pressure sufficient to activate the RAAS occurs with a relatively severe stenosis( at least 60 to 80% reduction in diameter)

15. Mechanism of hypertension 1-clip–2-kidney hypertension 1-clip–1-kidney hypertension

16. Distinguishing features from 1° HTN

17. Fibromuscular Dysplasia[FMD] FMD is a noninflammatory , nonatherosclerotic arteriopathy characterized by arterial medial smooth muscle cell proliferation and fibrosis Leads to development of arterial stenosis, occlusion, aneurysm, dissection, and arterial tortuosity most common cause of RVH in children and young adults Primarily involves renal and cerebral arteries

18. Epidemiology RAs are involved with FMD in 65% to 80% of cases(can be bilateral in 25% to 35% of adult cases) Cerebrovascular involvement is present in up to 65% of adult cases with renovascular FMD Among adults, more common in women [90 percent of FMD cases are in women] Prevalence is estimated to be 4 in 1000 Familial FMD occurs in approximately 10% of patients

19. Pathophysiology Unknown Numerous disturbances in vascular collagen and structural processes can result in the FMD angiographic phenotypes No unifying genetic mutation has been identified F actors implicated in the etiology of FMD include: cigarette smoking hormonal influences vascular trauma or stretching of the RA during development

20. Classification Angiographic appearance- most commonly used Multifocal FMD (more common) "string of beads“ appearance corresponds pathologically to medial fibroplasia and to perimedial fibroplasia Focal FMD (less common) circumferential or tubular stenosis appearance corresponds pathologically to intimal fibroplasia FMD generally involves the segment of RA beyond the first 2 cm from the ostium

21. Multifocal FMD Focal FMD

22. Clinical presentation Disease manifestations may result from the following mechanisms: Ischemia related to stenosis Dissection and occlusion of major arteries (renal infarction, stroke, myocardial infarction) Rupture of aneurysms Embolization of intravascular thrombi from dissection or aneurysms

23. Atherosclerotic Renal Artery Stenosis[ARAS] the most common cause of RVH in patients over the age of 50 occurs in patients with more generalized atherosclerosis associated with increased cardiovascular and mortality risk is a contributor to the development of end stage renal disease (ESRD) in up to 22% of incident ESRD

24. Epidemiology bilateral in 20% to 40% of patients usually involves the aortic orifice or the proximal main renal artery Estimates of prevalence vary widely A progressively higher rate in older patients Predictors of RA stenosis include:  history of hypertension  history of smoking  presence of CKD  the presence of abdominal bruits  coexisting peripheral vascular or coronary artery disease

25. Some patients will experience progressive RA luminal narrowing and develop RVH Progression is defined as greater than 25% further luminal diameter narrowing or progression to vascular occlusion progression in 30% over 3 years , more common in those with more than 60% stenosis Total occlusion is rare, reported in only 3%

26. Clinical presentation

27. Diagnosis of RVH INDICATIONS FOR TESTING clinical findings suggest a cause of secondary hypertension rather than primary hypertension patient does not appear to have another cause of secondary hypertension Renal revascularization or another intervention would be planned or considered if a significant stenotic lesion is found

28. Invasive testing indications Only for those patients who are thought to have a high likelihood of benefiting from the procedure Short duration of HTN before diagnosis of RVH Failure to medically control the BP Intolerance to optimal medical therapy Progressive kidney function impairment due to RVD Suspected FMD in young person-attempt to limit need for life long anti-HTN use Recurrent flash pulmonary edema or heart failure

29. Testing options Conventional direct angiography- gold standard to define the RA anatomy Noninvasive screening options : Duplex Doppler ultrasonography Computed tomographic angiography (CTA) Magnetic resonance angiography (MRA)

30. Duplex Ultrasound Measures -peak systolic velocity[PSV], renal aortic ratio[RAR], acceleration time and index, and intrarenal resistive index Normal PSV in RA is 120-160cm/s PSV > 200-220cm/s and RAR>3.5 indicate RAS of >60% narrowing The higher the PSV, the more severe the stenosis Resistive index- combined with Duplex US it predicts outcome after revascularization

31. Duplex US… Advantages relatively inexpensive and carries no risk most effective in detecting lesions of the main RA near the ostium monitoring for progression and changes in kidney size preferred test for evaluating for restenosis of a stented RA segment Limitations time consuming technically difficult little functional information regarding the kidney beyond the vascular lesion

32. MRA Advantage excellent visualization of the arteries and functional information about the kidneys avoiding radiation exposure Limitation interobserver variability overestimate luminal narrowing interference by motion and breathing artifact limited sensitivity for middle and distal vascular lesions and small accessory vessels Risk of NSF with gadolinium use

33. CTA Advantage imaging definition nearly equal to that of conventional angiography highly sensitive for identifying lesions in the mid and branch vessels[FMD] Limitation requires significantly more contrast

34. Tests of limited utility no longer considered suitable for initial testing Plasma renin activity[PRA] Peripheral venous PRA elevated in only 50 to 80 % of patients with RVH limited value for the diagnosis of RVH Measurement of renal vein renin Captopril renogram provides functional information regarding the size and excretory capacity of the kidney high negative predictive value for the presence of RVH when completely normal

35. Advantages Limitations

36. Diagnostic algorithm with suspicion of RAS

37. Treatment of FMD Options of management of HTN Medical treatment Revascularization Management algorithm of FMD

38. Revascularization Indication for revascularization recent-onset hypertension, particularly younger patients with focal FMD resistant hypertension despite compliance with an appropriate three-drug regimen unable to tolerate antihypertensive medications or who are noncompliant with their medication regimen Hypertensive children with renal artery FMD Adult with bilateral FMD or unilateral RA FMD to a single functioning kidney with unexplained progressive renal insufficiency due to IRD

39. P ercutaneous renal artery angioplasty (PTRA) is the treatment of choice, usually done without stenting High cure rate of HTN Complete cure [ normalization of BP without the need for medications] occurs in 35% to 45% of cases In over 85% of cases of FMD treated with PTRA, BP is improved with reduction in the number of antihypertensive medications

40. Predictors of response to intervention include: lower preintervention systolic BP younger age at treatment shorter duration of hypertension, and a positive pretreatment captopril renogram

41. Inadequate initial treatment or restenosis is most common with the string of beads angiographic variant can require more than one procedure intimal and adventitial variants of FMD are associated with higher rates of PTRA failure may require surgical revascularization for optimal management

42. Surgical revascularization The two main indications for surgery include: revascularization in children with focal FMD (usually intimal fibroplasia) if FMD is associated with renal artery aneurysm(s)

43. Medical treatment Choice of anti hypertension ACEI/ARBs are 1 st line Add thiazide diuretic or long acting CCB-if BP remains uncontrolled BP goal Same as other hypertensive patients Major potential complications Decline in eGFR Hyperkalemia

44. Patient monitoring Medical treatment alone : Follow up Serum Cr, and electrolytes- 1-2 weeks after initiation of ACEI/ARBs Serum Cr and Duplex ultrasound every 12 month Revascularization : Serum Cr and Duplex US at 1 st visit post procedure, then Q 6 month for 2 years and then yearly if stable If patient develops worsening/new HTN, unexplained increase in Cr, Duplex US should be done[if equivocal or poor quality do CTA]

45. Treatment of atherosclerotic RAS Options of management Medical treatment Revascularization Management algorithm of ARAS

46. Medical management 1 st line treatment of choice A ddressing all cardiovascular and renal risk factors: HTN- RAAS blockers Control DM Treat CKD complications-anemia, MBD Statins Anti platelets Smoking Cessation

47. Revascularization Percutaneous Renal artery stenting [PTRS] is the standard practice currently

48. Surgical revascularization Reserved for patients: failing best medical treatment and endovascular treatment is not feasible concomitant aortic disease that is not amenable to endovascular treatment considered in patients with total occlusion of the RA and abrupt loss of GFR for retrieval of kidney function

49. Takayasu Arteritis A rare inflammatory disorder involving renal vasculature causing RVH usually presents between the ages of 25 and 41 years but can also present in childhood Pathophysiology is unclear T heories include autoimmunity and hypersensitivity response to a variety of proposed antigens, including heat shock protein and Mycobacterium tuberculosis

50. Clinical presentation most often presents as RVH should be considered in any child or young adult with hypertension and/or asymmetric peripheral pulses or bruits Prodromal illness- precedes identification of RAS in 50% of cases After this active inflammatory phase, vascular stenoses can lead to sequelae depending on sites of involvement

51. Diagnosis requires arteriographic narrowing or occlusion of a vascular territory of the aorta, its branches, or large arteries not attributable to atherosclerosis, middle aortic syndrome, or FMD Distinguishable feature is presence of inflammatory thickening or edema of the vascular wall seen on imaging Treatment Corticosteroids or other immunomodulatory therapy during the inflammatory phase medical or interventional treatment to reduce organ ischemic injury

52. Coarctation of Aorta occurs in about 1 in 1550 births and accounts for about one third of all causes of RVH in infants Clinical presentation In previously undiagnosed adults, the classic presenting sign is hypertension Carotid bruit, palpable intercostal pulses radio-femoral pulse delay a harsh systolic blowing murmur is heard best over the posterior thorax Diagnosis MRA or CTA is necessary to confirm coarctation in adults

53. Treatment- endovascular or surgical repair Indications for the treatment of coarctation in adults: upper limb hypertension and a greater than 20 mm Hg systolic BP gradient across the stenosis with evidence of significant collateral flow Success rates in terms of cure of hypertension range from 69% to 80%, with highest chance for cure and best survival data when treated in childhood under the age of 10

54. Endocrine causes of Hypertension

55. Introduction Endocrine causes for hypertension may be present in more than 12% of all hypertension cases frequently occurs in the absence of clear signs and symptoms or abnormalities in routine biochemical tests Is often remains undiagnosed diagnosis may offer the chance for cure of hypertension

56. Primary aldosteronism[PA] It is a potentially curable form of hypertension Prevalence varies from <2 to ~15% of hypertensive individuals Excess aldosterone production is independent of the renin-angiotensin system consequences are sodium retention , hypertension , hypokalemia , low PRA , cardiovascular disease , and kidney damage

57. Pathogenesis of Aldosterone-Dependent Hypertension

58. Etiologies of PA Can be sporadic or familial Sporadic PA The two most common causes of sporadic primary aldosteronism are aldosterone-producing adenoma[APA]- typically unilateral and is < 3cm in diameter bilateral adrenal hyperplasia Together account for 90 % of PA

59. Other less common causes: bilateral adrenocortical hyperplasia (idiopathic hyperaldosteronism) adrenal carcinoma ectopic malignancies

60. Familial PA- 4 types Familial hypertension type I (FH-I) [ glucocorticoid-remediable aldosteronism (GRA)] crossover between the CYP11B1 and CYP11B2 genes transmitted in an autosomal dominant pattern Should be considered in children or young adults with refractory hypertension or a family history of hypertension at a young age or history of premature hemorrhagic stroke Genetic testing Low dose corticosteroids dramatically improves BP control

61. Epidemiology primary aldosteronism is more common than previously thought Accounts for 2- 15 % of hypertensive patients Higher rate in patients with treatment resistant hypertension typically of 20% to 40% and as high as 67% in some studies Usually in 2 nd to 5 th decade of life

62. Clinical manifestation Most patients are asymptomatic and have no distinguishing characteristics from essential hypertension If symptomatic HTN is usually mild to moderate , sometimes may be refractory frank or easily provoked hypokalemia- prevalence of PA may reach up to 40-50% Clues for secondary hypertension If left untreated, it is associated with increased cardiovascular events and a variety of neuropsychiatric disorders

63. Diagnosis Who to screen for PA? patient with refractory hypertension patient with spontaneous or easily provoked hypokalemia adrenal adenoma on abdominal imaging in patients under the age of 40 years screening for primary aldosteronism is recommended before initiating antihypertensive therapy with MR blockers If already started- withhold for 2-4 weeks before testing

64. Aldosterone to renin ratio[ARR] a useful screening test obtained in ambulatory patients in the morning elevated aldosterone value in combination with an elevated ARR strongly suggests primary aldosteronism A ratio >30:1 in conjunction with a PA concentration >555 pmol /L (>20 ng/dL) has a sensitivity of 90% and a specificity of 91% for an aldosterone-producing adenoma.

65. Confirmatory testing Used if diagnosis of PA is in doubt

66. Imaging Adrenal CT should be done in all patients diagnosed with PA HRCT can identify tumors as small as 0.3cm and is positive for adrenal tumor in 90% of the time. Most APAs are large enough (>1 cm) to be identified by CT nonfunctional adrenal adenomas are common especially in Age>40 Adrenal hyperplasia, as a cause of primary aldosteronism, is not detectable with current CT or MR imaging techniques

67. Adrenal Vein Sampling Is a definitive test for determining unilateral or bilateral disease should be used in the patient who has a high pretest likelihood of unilateral disease patient with PA known to have an adrenal adenoma patient with severe PA not responsive to medical therapy ratio of adrenal vein aldosterone to adrenal vein cortisol is calculated for each adrenal vein lateralization index: greater than 2.0 supports a diagnosis of an APA( cut-off is not 100% specific)

68. Treatment Two options: Surgical and medical Treatment Surgical[ Adrenalectomy] Adrenalectomy is more effective than medical treatment for unilateral APA 30% to 60% chance of hypertension cure with adrenalectomy Those not cured have a greater than 95% chance for BP improvement Laparoscopic Adrenalectomy is better compared with open surgical approach

69. Medical Rx[MRAs] For which patients? For Patients who are not candidates for surgical adrenalectomy or who have bilateral aldosterone production treatment options are spironolactone and eplerenone Spironolactone as the preferred initial agent due to its greater treatment efficacy should be started at modest doses[Spironolactone PO 25-50mg/d] and titrated slowly on a 2-4 week basis

70. usually results in dramatically improved BP control Both systolic BP and diastolic BP frequently decrease by about 25 mm Hg over a few weeks to months Side effects are usually easily managed and include: Muscle cramps neuropsychiatric side effects Hyperkalemia Other agents for HTN- if symptoms uncontrolled with high doses of MRAs ENaC inhibitors such as amiloride or triamterene Aldosterone synthase inhibitors are a new treatment option in development

71. Pheochromocytoma Pheochromocytomas and paragangliomas are catecholamine-producing tumors derived from the sympathetic or parasympathetic nervous system Mimic lots of other diseases and diagnosis is frequently delayed or missed altogether secrete norepinephrine, epinephrine, and dopamine

72. Epidemiology Estimated to occur in 2–8 of 1 million persons per year, ~0.1% of hypertensive patients Mean age at diagnosis is 40 years equally common in males and females Classic “ rule of tens ” of Pheochromocytoma ~10% are bilateral 10% are extra-adrenal 10% are metastatic 10% occur in children 10% are malignant

73. Etiology and Pathogenesis Most cases are sporadic( with unknown etiology) and some are familial Sporadic cases are usually unicentric and unilateral familial pheochromocytomas are often multicentric and bilateral Familial tumors typically present at a younger age than sporadic neoplasms several familial disorders associated with adrenal pheochromocytoma( VHL, MEN2, NF1 )

74. Clinical presentation Symptoms occur in 50% of patients and typically paroxysmal C lassic triad : episodes of palpitation, headache, and profuse sweating are typical presence of all three manifestations in association with hypertension makes pheochromocytoma a likely diagnosis Rarely patients may present with pheochromocytoma crisis May have hypertension or hypotension, hyperthermia (temperature >40°C), mental status changes, and other organ dysfunction

75. Hypertension is the dominant sign, classically it is episodic hypertension. 5-15% may have normal BP during episodes of hormone release: anxious and pale, tachycardia and palpitations paroxysms generally last <1 h precipitated by surgery, positional changes, exercise, pregnancy, urination, and medications(TCAs, Opiates, metoclopramide)

76. When to suspect pheochromocytoma? The classic triad symptoms with/without hypertension Hyperadrenergic spells Onset of hypertension at a young age ( eg , <20 years), resistant hypertension, or hypertension with new-onset or atypical diabetes mellitus familial syndromes, family history of pheochromocytoma adrenal incidentaloma with or without hypertension Idiopathic dilated cardiomyopathy

77. Diagnosis

78. Typical pheochromocytoma (adrenal unilateral)

79. Treatment U ltimate therapeutic goal: Complete tumor removal by partial or total adrenalectomy Preoperative preparation BP control BP should be consistently <160/90 mmHg 7 to 21 days of α-adrenoceptor blockade(oral phenoxybenzamine, 0.5–4 mg/kg of body weight) Oral prazosin or intravenous phentolamine can be used to manage paroxysms

80. β-blockade added later (if necessary to control BP and tachycardia) liberal salt intake and hydration to avoid severe orthostasis N.B . β-Blocker monotherapy is contraindicated because unopposed α-adrenergic stimulation can cause hypertensive crisis

81. Surgery should be done with multidisciplinary team laparoscopic approach better acceptance than open adrenalectomy Intraoperative BP control Phentolamine, sodium nitroprusside, and magnesium sulfate hypotension usually responds to volume infusion

82. Postoperative period catecholamine normalization should be documented ACTH test should be used to exclude cortisol deficiency when bilateral adrenal cortex– sparing surgery has been performed Complications should be looked for(Hypotension and hypoglycemia)

83. Follow up life-long biochemical monitoring at least annually and in the event of symptoms suggestive of recurrence BP usually improves with tumor removal but in 25% can remain persistently elevated

84. Cushing syndrome Constellation of clinical features that result from chronic exposure to excess glucocorticoids of any etiology ACTH-dependent - pituitary adenoma (Cushing disease), ectopic secretion of ACTH by nonpituitary tumor ACTH-independent - adrenocortical adenoma, adrenocortical carcinoma, nodular adrenal hyperplasia Iatrogenic - exogenous glucocorticoids

85. Epidemiology incidence of endogenous Cushing syndrome is 5 to 10 cases per 1 million population per year Cushing disease and cortisol-secreting adrenal tumors: 4X more common in females Overall, iatrogenic Cushing’s is the most common cause Among endogenous Cushing’s syndrome- Pituitary adenoma is the most common cause(90%) Primary, adrenal cause accounts for Only 10% of patients

86. Mechanisms of HTN Hypertension is present in 80% of patients Mechanisms: enhanced pressor responsiveness to catecholamines and Ang II heightened cardiac inotropic sensitivity to β-adrenergic stimulation increased plasma volume cardiovascular inflammatory, hypertrophic, and fibrotic changes from cardiac and vascular mineralocorticoid receptor activation

87. Clinical manifestations

88. Diagnosis

89. Treatment Tumor Removal Adrenal adenoma-unilateral adrenalectomy Cushing’s disease: endoscopic transsphenoidal approach E ctopic ACTH syndrome- locate tumor and remove M edical therapy - antiglucocorticoid (metyrapone and ketoconazole) in patients with very severe, overt Cushing's to rapidly control the cortisol excess until surgery is done metastasized, glucocorticoid-producing carcinomas

90. After cure of Cushing syndrome, approximately 30% of patients have persistent hypertension Use of antihypertensive agents No evidence supports the use of any antihypertensive class over another

91. HYPOTHYROIDISM HTN is 1.5 to 2 times more common in hypothyroid patients than the general population. P athogenesis of HTN is multifactorial increased total body sodium and peripheral vascular resistance increased aortic stiffness, impaired endothelial function with loss of endothelial-dependent vasodilation Increased plasma catecholamine,cortisol and aldosterone Thyroid replacement therapy cures the HTN in most patients

92. HYPERTHYROIDISM HTN is common in hyperthyroidism- 60% in toxic adenoma and 30% in Graves disease. Mechanism of HTN: Increased cardiac output- by 50% to 300% I ncreased myocardial contractility, tachycardia, decreased peripheral vascular resistance, and Expanded blood volume β- Blockers - first-line therapy for hyperthyroidism-associated HTN. Treatment of hyperthyroidism often normalize the increased SBP

93. Neurogenic Hypertension

94. Hypertension After Spinal Cord Injury Autonomic dysreflexia occurs in up to 70% of persons after spinal injury, most often during the first 2 to 4 months after injury Definition : an increase in SBP by at least 20% associated with a change in heart rate and accompanied by at least one sign (sweating, piloerection, facial flushing) or symptom (headache, blurred vision, stuffy nose) Complications develop if left unrecognized: posterior leukoencephalopathy, ICH, SAH, seizures, arrhythmia, pulmonary edema, retinal hemorrhage, and, rarely, coma or death

95. The spinal cord lesion is typically at or above the sixth thoracic spinal level Uninhibited or exaggerated sympathetic responses to noxious stimuli below the level of the injury lead to diffuse vasoconstriction and hypertension I nciting events : most commonly overdistended urinary bladder and fecal impaction. Others: infections, pressure ulcers, urologic and endoscopic procedures, sympathomimetic medications A compensatory parasympathetic response produces bradycardia and vasodilation above the level of the lesion

96. Clinical Feature A bove the lesion level pulsatile headache, blurred vision, anxiety, nasal congestion, nausea, and sweating Flushed, sweaty skin is due to brainstem parasympathetic activation At and below the lesion : the skin remains pale, cool, and dry. Heart rate can be quite variable from bradycardia to tachycardia. The hallmark physical finding is elevated BP

97. Treatment P reventive measures : proper bowel, bladder, and skin care BP management initial treatments: place patient upright with the legs lowered and remove any possible noxious stimuli Look for and treat common triggers: urinary retention or constipation Pharmacologic treatment : if SBP elevation of 150 mm Hg or greater that persists after the preceding interventions Use rapid-acting, short-lived agents- Nitroglycerine, Prazosin, CCB, ACEI

98. References Harrison’s Principles of Internal Medicine 21 st edition Comprehensive Clinical Nephrology 6 th edition Oxford Textbook of Clinical Nephrology 4 th edition KDIGO 2021 CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF BLOOD PRESSURE IN CHRONIC KIDNEY DISEASE UpToDate

99. Thank you