Pathophysiology Of Kidney Disease And Hypertension Pdf
File Name: pathophysiology of kidney disease and hypertension .zip
- Hypertension in Chronic Kidney Disease: Navigating the Evidence
- Current Strategies for Management of Hypertensive Renal Disease
- Hypertension in Diabetic Nephropathy: Epidemiology, Mechanisms, and Management
Tedla, A. Brar, R. Browne, C.
Hypertension in Chronic Kidney Disease: Navigating the Evidence
Chronic kidney disease CKD is an increasingly prevalent condition globally and is strongly associated with incident cardiovascular disease CVD. Control of hypertension is important in those with CKD as it leads to slowing of disease progression as well as reduced CVD risk.
Existing guidelines do not offer a consensus on optimal blood pressure BP targets. Therefore, an understanding of the evidence used to create these guidelines is vital when considering how best to manage individual patients. Patients with CKD and hypertension will often require a combination of antihypertensive medications to achieve target BP.
Managing hypertension in the context of haemodialysis and following kidney transplantation presents further challenges. Novel therapies may enhance treatment in the near future. Hypertension is both a cause and effect of CKD and contributes to its progression [ 7 — 9 ].
As eGFR declines, the incidence and severity of hypertension increase [ 5 ]. When both exist together the risks of CVD morbidity and mortality are substantially increased [ 10 ]. A number of mechanisms contribute to the development of hypertension in CKD and these influence its management Fig.
Increase in sympathetic tone, brought about by afferent signals generated by functionally declining kidneys, contributes to the development of hypertension in CKD [ 15 ]. As eGFR declines there is an upregulation of the renin—angiotensin—aldosterone system RAAS which promotes salt and water retention [ 16 ].
This is compounded by an increased salt sensitivity of BP [ 17 ]. Increased arterial stiffness is also seen throughout the spectrum of CKD [ 19 ], is implicated in the development of hypertension [ 20 ], and is an independent risk factor for CVD events [ 21 ]. Once hypertension has developed, several factors, including increased oxidative metabolism, with resultant relative renal hypoxia, may drive further progression of BP and CKD [ 22 , 23 ].
Pathogenesis and management flow-chart of hypertension in chronic kidney disease. This is controlled by several factors including diurnal variations in autonomic function, salt excretion and the RAAS [ 24 ]. For management of hypertension to be effective, accurate BP measurements are essential. In practice, the treatment of hypertension is often based on clinic or office BP recordings [ 27 ].
These may be inaccurate due to lack of repeat measurements, diurnal variation in BP and white-coat hypertension [ 28 ]. Thus, this snapshot of BP may not accurately define the clinical problem. In order to identify these and institute treatment accordingly, more robust methods of measuring BP should be used. Home BP monitoring is an alternative strategy that is less resource intensive. Those who obtain home readings demonstrate better overall BP control than those who do not [ 30 ].
Current hypertension guidelines reflect this, with the American College of Cardiology ACC guidelines supporting out-of-office BP measurement to confirm the diagnosis of hypertension and for titration of BP-lowering medication in all patients [ 31 ]. To ensure accuracy, only validated home BP devices should be used [ 32 ]. Proteinuria is an important marker of renal damage and is incrementally and independently associated with CKD progression and incident CVD [ 10 ].
The most practical way to measure proteinuria is with a protein-to-creatinine ratio PCR obtained from a spot urine sample. Total daily proteinuria can be obtained via a h urine collection or extrapolated from a PCR or ACR measurement [ 35 ]. Although h urine collection remains the gold standard method for quantification of proteinuria, susceptibility to patient and sampling errors can lead to inaccuracies [ 36 ]. Relationship between measurement methods are not exact and will depend on multiple variables.
In addition to its antihypertensive effects, the impact of a drug on proteinuria is an important consideration when managing hypertension in CKD. Thus, these medications are considered first-line therapy for those with proteinuric CKD [ 31 ]. Guidelines offer the treating clinician a rapid, evidence-based, expert opinion regarding the management of certain conditions.
Often criticised for a lack of flexibility, however, they are seen by some as unhelpful due to the complexities involved in clinical decision-making. Guidelines governing the management of patients with CKD are relatively few in relation to other conditions of similar prevalence. This may, in part, reflect the relative dearth of high-quality clinical trials in CKD.
Despite this, guidelines outlining optimal treatment for CKD patients with hypertension are important, particularly as many of these patients are jointly managed in primary care. To understand the differences between these guidelines one must consider the evidence used to create them Fig. Timeline of landmark randomised trials comparing standard with intensive blood pressure control.
However, no such benefit was seen in those without proteinuria [ 40 ]. The addition of a CCB did reduce BP; however, this did not translate into improved renoprotection [ 48 ]. Guidelines published in the wake of these landmark studies reflected these results, suggesting lower targets only for those with significant proteinuria. However, these studies did not consider the potential benefits of intensive BP control on cardiovascular endpoints.
Despite a sustained difference in attained BP between the standard and intensive treatment groups, the risk of death from CVD did not differ significantly.
There was, however, a reduced risk of stroke with intensive BP control. The intensive treatment group demonstrated a statistically significant reduction in the primary outcome, a composite of MI, acute coronary syndrome, stroke, heart failure or death from CVD.
A reduction in the secondary outcome of death from any cause was also significant. The effect size was so large the trial was stopped prematurely after three of its projected 5-year duration. Despite this, there was no effect on renal outcomes, including the rate of eGFR decline. It should be noted that the method of BP measurement used may have a significant impact on the outcome of any trial.
This may be why such a low target BP was found to be beneficial. Notably, the risk of developing acute kidney injury AKI was increased in the intensive treatment group. Additionally, in those with normal renal function at baseline, the risk of developing CKD during the study was higher with intensive treatment. An analysis by Zhang et al. Accordingly, guidelines vary.
Perhaps this could be interpreted as a prioritisation of cardiovascular protection over renoprotection by the Americans, and vice versa by the Europeans. Examining the available evidence allows understanding of the rationale behind these decisions and thus a basis on which to create individualised treatment plans that take into account CVD risk, rate of projected eGFR decline, co-morbidities and other patient characteristics. BP goals are likely to change as an individual ages or develops more advanced disease.
Achieving BP targets is challenging. Results in those with CKD suggest that it may be even more challenging to achieve BP goals than in the general hypertension population [ 55 ]. Despite treatment with non-pharmacological interventions and multiple antihypertensive agents, the majority of CKD patients fail to reach target BP [ 56 ]. There are a number of non-pharmacological treatments for hypertension in the context of CKD. A study by Slagman et al.
There are some in whom the effects of dietary sodium have little impact on BP. In practice, dietary sodium restriction can be difficult to achieve. Urinary sodium measurements by Slagman et al. The benefits of a multidisciplinary approach have also been demonstrated in CKD. A systematic review by Santschi and colleagues [ 62 ] has shown improved attainment of BP goals in hypertensive patients following the introduction of community pharmacists.
Despite the benefits of non-pharmacological interventions in CKD, antihypertensive medications are usually also required [ 56 ].
The choice of drug should therefore consider the balance of risk reduction required by the individual. Combination drug therapy is frequently needed to achieve BP targets [ 64 ], and thus the risks of polypharmacy need also be considered.
ACE inhibitors and angiotensin II receptor antagonists blockers ARBs have both cardioprotective and renoprotective properties and are therefore of particular value in patients with CKD [ 42 ]. Importantly, however, these agents offer a BP-independent reduction in proteinuria in both diabetic and non-diabetic CKD and are therefore generally accepted as first-line management of hypertension in patients with proteinuric CKD [ 39 , 64 — 66 ]. A systematic review carried out by Casas and colleagues [ 67 ] demonstrated that the improved renal outcomes associated with RAAS blockade are most likely due to a BP-lowering effect only, and could therefore be mirrored by other antihypertensives if the same reduction in BP was achieved.
Consequently, although ACE inhibitors may be used as first-line agents in those with hypertension and non-proteinuric CKD, CCBs and thiazide or thiazide-like diuretics should also be considered as alternative first-line choices in this population [ 46 ].
It has therefore been hypothesised that the addition of an ARB to those already established on ACE inhibition might improve cardiovascular and renal outcomes. Combination therapy was associated with an increased incidence of adverse effects with no significant reduction in the primary outcome of death from CVD, MI, stroke or heart failure. Notably, these studies included subjects at high risk of renal vascular disease, in whom GFR is to some extent dependent on a functional RAAS.
Whether this translates to a greater cardiovascular and renal benefit is currently unclear. A rise in serum creatinine is often seen after initiation of RAAS blockade due to a reduction in intraglomerular pressure [ 70 ].
The significance of this transient fall in eGFR is unclear. In contrast, after a mean follow-up period of 3. An observational study by Ahmed et al. Until results from this trial are available, the question of whether or not to initiate or continue RAAS blockade in those with advanced CKD remains uncertain.
Diuretic therapy can reduce volume expansion and has been shown to improve left ventricular mass index and arterial stiffness in those with CKD [ 76 , 77 ]. Thus, diuretics are frequently used as part of combination drug therapy in CKD and offer antihypertensive and cardioprotective effects [ 76 ]. In non-proteinuric CKD, monotherapy with a thiazide such as bendroflumethiazide or a thiazide-like diuretic such as indapamide may have a role and should be considered as a potential for first-line therapy [ 43 ].
Treatment with a diuretic may also reverse the loss of physiological nocturnal dip in BP described in CKD [ 78 ]. Loop diuretics such as furosemide are valuable, although higher doses are often required in those with a lower eGFR as the tubular mechanism of action of these drugs relies first on glomerular filtration. The combination of a loop and thiazide diuretic is particularly powerful, and care should be taken to avoid fluid depletion. Diuretics should generally be avoided in patients with polycystic kidney disease due to accelerated cyst growth and loss of excretory function associated with their use [ 79 ].
Mineralocorticoid receptor antagonists blockers such as spironolactone effectively reduce BP in CKD but run the risk of exacerbating hyperkalaemia [ 80 ].
These agents have been demonstrated to improve systolic and diastolic function in early CKD and therefore may be of particular value in patients with concomitant left ventricular dysfunction [ 81 ]. It is unclear whether this effect is due to BP lowering alone.
In hypertensive patients without CKD, spironolactone is more effective than bisoprolol or doxazosin at reducing BP when used as a fourth-line add-on therapy [ 83 ]. Dihydropyridine CCBs such as amlodipine can be used as first-line therapy in non-proteinuric CKD, either alone or in combination. Non-dihydropyridine CCBs such as verapamil have a superior effect on proteinuria reduction and are as effective as dihydropyridine CCBs in terms of BP control [ 84 ].
Current Strategies for Management of Hypertensive Renal Disease
Annual incidence rates for end-stage renal disease, adjusted for age, race, and sex, to Annual incidence rate for end-stage renal disease by renal diagnosis, adjusted for age, race, and sex, to DM indicates diabetes mellitus; HTN, hypertension. Arch Intern Med. The incidence of hypertensive end-stage renal disease continues to increase annually.
Chronic kidney disease CKD is defined as persistent kidney damage accompanied by a reduction in the glomerular filtration rate GFR and the presence of albuminuria. The rise in incidence of CKD is attributed to an aging populace and increases in hypertension HTN , diabetes, and obesity within the U. CKD is associated with a host of complications including electrolyte imbalances, mineral and bone disorders, anemia, dyslipidemia, and HTN. It is well known that CKD is a risk factor for cardiovascular disease CVD , and that a reduced GFR and albuminuria are independently associated with an increase in cardiovascular and all-cause mortality. Multiple guidelines discuss the importance of lowering blood pressure BP to slow the progression of renal disease and reduce cardiovascular morbidity and mortality. Hypertension is one of the leading causes of CKD due to the deleterious effects that increased BP has on kidney vasculature.
Hypertension in Diabetic Nephropathy: Epidemiology, Mechanisms, and Management
With chronic kidney disease CKD , kidneys become damaged over time or cannot clean the blood as well as healthy kidneys. Diabetes and high blood pressure are the major causes of CKD in adults. Other risk factors include heart disease, obesity, a family history of CKD, past damage to the kidneys, and older age. Keep kidneys healthy by managing blood sugar and blood pressure. If kidney damage is severe and kidney function is very low, dialysis or a kidney transplant is needed for survival.
Голос Дэвида точно вел ее, управляя ее действиями. Она бросилась к лестнице и начала подниматься к кабинету Стратмора. За ее спиной ТРАНСТЕКСТ издал предсмертный оглушающий стон. Когда распался последний силиконовый чип, громадная раскаленная лава вырвалась наружу, пробив верхнюю крышку и выбросив на двадцать метров вверх тучу керамических осколков, и в то же мгновение насыщенный кислородом воздух шифровалки втянуло в образовавшийся вакуум. Сьюзан едва успела взбежать на верхнюю площадку лестницы и вцепиться в перила, когда ее ударил мощный порыв горячего ветра.
Он шарахался из стороны в сторону, не выпуская Сьюзан из рук, стараясь не дать Стратмору возможности выстрелить. Движимый страхом, он поволок Сьюзан к лестнице. Через несколько минут включат свет, все двери распахнутся, и в шифровалку ворвется полицейская команда особого назначения. - Мне больно! - задыхаясь, крикнула Сьюзан.
DIABETES AND KIDNEY DISEASE-DIABETIC NEPHROPATHY
Главный криптограф АНБ испробовала все - подмену букв, шифровальные квадраты, даже анаграммы. Она пропустила эти слова через компьютер и поставила перед ним задачу переставить буквы в новую фразу. Выходила только абракадабра. Похоже, не один Танкадо умел создавать абсолютно стойкие шифры. Ее мысли прервал шипящий звук открываемой пневматической двери. В Третий узел заглянул Стратмор. - Какие-нибудь новости, Сьюзан? - спросил Стратмор и тут же замолчал, увидав Грега Хейла.
Она не могла припомнить, чтобы когда-то отменялось дежурство, но Стратмор, очевидно, не хотел присутствия непосвященных. Он и мысли не допускал о том, что кто-то из сотрудников лаборатории узнает о Цифровой крепости. - Наверное, стоит выключить ТРАНСТЕКСТ, - предложила Сьюзан. - Потом мы запустим его снова, а Филу скажем, что ему все это приснилось. Стратмор задумался над ее словами, затем покачал головой: - Пока не стоит.
Сьюзан остановилась, собираясь с духом. Звук выстрела продолжал звучать у нее в голове. Горячий пар пробивался через люк подобно вулканическим газам, предшествующим извержению. Проклиная себя за то, что не забрала у Стратмора беретту, она пыталась вспомнить, где осталось оружие - у него или же в Третьем узле. Когда глаза Сьюзан немного привыкли к темноте, она посмотрела на дыру, зияющую в стеклянной стене. Свечение мониторов было очень слабым, но она все же разглядела вдали Хейла, лежащего без движения там, где она его оставила. Стратмора видно не .
Он ничего не спрашивал про ТРАНСТЕКСТ. - Нет.
Расход энергии даже чуть выше обычного: более полумиллиона киловатт-часов с полуночи вчерашнего дня. - И что все это. - Не знаю. Все это выглядит довольно странно.
Когда я вернулся, немца уже не. - Вы не знаете, кто он. - Какой-то турист. - Вы уверены.
Попробовал пошевелиться и ощутил резкую боль. Попытался что-то сказать, но голоса не. Зато был другой голос, тот, что звал .