Kidney and Hypertension in Diabetes Mellitus


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Ethical considerations

Recently, data from normal patients identified those with elevated blood pressure outside of the office but normal ones within it. Self- and home-based blood pressure measurement HBP. Equally important is the notation that those who engage in HBP adhere to their antihypertensive regimens more fully.

Based on the Ohasama Study, blood pressure measurements taken in the morning and evening yield additional prognostic information in this regard. To most closely simulate ABPM, obtain blood pressure readings twice weekly during initial drug titration, before breakfast, and after the evening meal. After blood pressure has stabilized, obtain readings every 1—2 weeks. Finally, blood pressure cuffs should be calibrated with an accurate, physician-approved oscillometric or, if available, mercury-based blood pressure—measuring device, which are still used in the United States, albeit less frequently due to restrictions governing the use of elemental mercury.

Hypertensive DKD patients, especially African Americans, harbor tremendous risk for kidney failure, 2 and intensive therapy is unequivocally protective. Thus, attaining and maintaining recommended blood pressure goals is a clinical mandate. However, DKD patients frequently require three to four agents to achieve blood pressure goals. Angiotensin-converting enzyme ACE inhibitors and angiotensin 2 receptor blocker ARB combinations, especially with diuretics or calcium channel blockers CCBs , make financial and prescriptive sense i.

CCBs are divided into dihydropyridine and nondihydropyridine classes. Nifedipine and felodipine are examples of the former, and diltiazem and verapamil are examples of the latter. ACE inhibitors are the cornerstone of antihypertensive, renoprotective, cardiovascular, risk-modifying therapy in diabetes; they retard progression of DKD and reduce proteinuria in type 1 and type 2 diabetes. Some posit that ACE inhibitors confer special cardiovascular protective and antiproteinuric effects, whereas others contend that attainment of blood pressure targets is the key to success for any antihypertensive class of drugs.

ARBs have the largest data set for slowing progression of renal disease in type 2 diabetes. ARBs in both trials reduced development of heart failure but not of cardiovascular mortality. An IDNT post hoc analysis revealed improved cardiovascular outcomes by achieving systolic blood pressure readings near mmHg.

Therefore, maximally tolerated doses of anti-RAAS drugs are the rule, not the exception. Combination therapy composed of an ACE inhibitor and an ARB generally offers a small additive blood pressure—reducing effect of 2—4 mmHg and a synergistic proteinuria-reducing effect. Most DKD patients are volume expanded, necessitating sodium restriction and diuretic treatment. The importance of the diuretic component is underscored by the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ALLHAT , in which equivalent protection against coronary heart disease death and nonfatal myocardial infarction was shown in comparisons among mildly hypertensive diabetic subjects and nondiabetic subjects treated with ACE inhibitor, amlodipine, or the diuretic chlorthalidone.

African Americans had significantly lower blood pressure and superior outcomes with diuretic monotherapy at the expense of worsened glycemic control, hyperuricemia with or without gout, hypokalemia, and hyponatremia. The nondihydropyridine CCBs diltiazem and verapamil are lipid- and glucose-neutral agents and may reduce proteinuria. Dihydropyridine CCBs, such as amlodipine and nifedipine, increase proteinuria when used alone, 32 but this adverse effect is abrogated during concurrent ACE inhibitor or ARB administration.

Notably, amlodipine increased heart failure compared to chlorthalidone, when used alone in patients with diabetes in the ALLHAT. Beta blockers are used with other drugs and are indicated in patients who have had myocardial infarctions. Their track record in primary prevention of cardiovascular events in hypertension is inferior to other agents including diuretics, and this observation prompted the British Health Service to remove them from its list of first-line antihypertensive agents. The beta blocker carvedilol is a combined nonselective beta- and alpha-1 adrenergic inhibitor and is now available as a generic.

This agent is associated with improved survival in heart failure. Collaborative management by an advanced nurse practitioner, a nurse with expertise in hypertension, and a physician has been shown to improve blood pressure control in diabetic hypertensive patients. The latter is highly important because DKD, in the presence of ongoing tobacco use, can sound the death knell for the kidneys and obviates the antihypertensive effects of many blood pressure—reducing drugs.

Any use of alternative or over-the-counter medications should be evaluated. Dietary instructions must emphasize the central importance of limiting sodium to 2, mg daily to potentiate the action of antihypertensive and antiproteinuric agents. Weight reduction is important, and vigilance for aggravating factors of hypertension is advised.

There are minimal data regarding the frequency of additional secondary causes of hypertension in patients with preexistent CKD, with the exception of obstructive sleep apnea. Evaluation of medications that may aggravate hypertension Table 1. Sleep apnea or sleep deprivation Polycystic ovary syndrome Primary aldosteronism in any of its several forms Persistent hypokalemia, hypernatremia, or metabolic alkalosis are clues to the diagnosis. Weight loss and exercise are potent blood pressure—reducing activities, if practiced consistently.

The choice of additional antihypertensives is limited by a general lack of evidence base in patients with CKD. Recent data involving long-acting nitrates for the treatment of isolated systolic hypertension is promising, but a well-informed recommendation cannot be proffered. Unfortunately, none of these medications has a CVD risk reduction database.

A careful review of the indications and side effects of these agents before prescribing is necessary, or referral to a hypertension specialist or a physician familiar with these medications is obligatory. These drugs are undergoing study as agents for additional control of proteinuria in CKD Stages 1 and 2. Reversible and mild GFR reductions have been documented.

Notably, spironolactone has effectively treated resistant hypertension in patients with normal or near-normal kidney function. At a minimum, frequent and careful follow-up of serum potassium levels must be carried out in such circumstances. Patients should return for follow-up twice monthly until the goal blood pressure is achieved and monthly for 3 months thereafter. Medication reconciliation, financial considerations, and practices that increase drug adherence should be reviewed.


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Referral to a hypertension specialist is encouraged when blood pressure control requires more than 4—6 months because data from several recent trials show decreased cardiovascular events in patients when blood pressure targets are attained within 6 months. Lastly, parameters such as proteinuria should be monitored in conjunction with electrolytes, BUN, and serum creatinine. Control of hypertension in DKD requires a collaborative network among patients, primary care providers, endocrinologists, and nephrolgists. Careful blood pressure measurement, a multiple risk factor modification strategy, and persistent and judicious RAAS blockade in combination with diuretics and add-ons should result in good blood pressure control in a majority of patients.

Engaging patients and their families through HBP, lifestyle modification, and collaboration with clinic nurses, advanced practice nurses, and clinical pharmacists will facilitate success, thereby reducing the extraordinarily high CVD risk burden of DKD and retarding progression to kidney failure. She is a consultant for HomeMedics. These companies make pharmaceutical products or monitoring devices for the treatment of hypertension. We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail.

We do not capture any email address. Skip to main content. Diabetes Spectrum Jan; 21 1: Abstract In Brief Diabetes is associated with markedly increased cardiovascular risk, a risk compounded with imposition of chronic kidney disease CKD. Pathophysiology of Hypertension Hypertension in CKD is marked by extracellular fluid volume expansion, sympathetic nervous system activation, and vasoconstrictor accumulations of endothelin and asymmetric dimethylarginine, an endogenous nitric oxide inhibitor. Evaluation of Hypertensive Patients A careful patient history includes the following: View inline View popup Download powerpoint.

High Blood Pressure and Diabetic Kidney Disease

Blood pressure measurement modalities Office-based blood pressure measurement OBP. Initial considerations Hypertensive DKD patients, especially African Americans, harbor tremendous risk for kidney failure, 2 and intensive therapy is unequivocally protective. Diuretic agents Most DKD patients are volume expanded, necessitating sodium restriction and diuretic treatment.

CCBs The nondihydropyridine CCBs diltiazem and verapamil are lipid- and glucose-neutral agents and may reduce proteinuria. Beta blockers Beta blockers are used with other drugs and are indicated in patients who have had myocardial infarctions. Resistant Hypertension There are minimal data regarding the frequency of additional secondary causes of hypertension in patients with preexistent CKD, with the exception of obstructive sleep apnea.

DIABETES AND KIDNEY DISEASE-DIABETIC NEPHROPATHY

Clinic Follow-up Patients should return for follow-up twice monthly until the goal blood pressure is achieved and monthly for 3 months thereafter. Summary and Conclusions Control of hypertension in DKD requires a collaborative network among patients, primary care providers, endocrinologists, and nephrolgists. Prevalence of chronic kidney disease in the United States.

Preserving renal function in adults with hypertension and diabetes: Am J Kidney Dis Prospective Diabetes Study Group: Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med Jacob J , Tsao PS: Asymmetrical dimethylarginine in renal disease: Am J Nephrol Relationship between arterial hypertension and renal damage in chronic kidney disease: Pathophysiology of hypertensive renal damage: Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: Intensive therapy reduced both microvascular and macrovascular disease.

The main issues for optimal management of diabetic nephropathy are listed in Table I. For BP attainment and optimal reductions in very high albuminuria, a low protein 0. Several randomized trials have demonstrated improvements in BP with dietary sodium restriction, with associated reductions in cardiovascular disease end points. Patients with CKD are generally less able to excrete a sodium load, making the potential benefit even greater, although there is little data available.

This is a change from prior guidelines that suggested lower, more aggressive, BP goals. Importantly, the prior recommendations were not based on a large body of randomized-control trial evidence. Following recent publication of these guidelines, a monumental meta-analysis of outcome trials involving anti-hypertensive therapy in patients with type 2 diabetes was published. Interestingly, this meta-analysis also assessed CKD progression end points and changes in albuminuria.

Consistent with current Kidney Disease: However, the new development of albuminuria, or worsening of already present albuminuria, was reduced with a mmHg decrease in systolic BP. The difference between these two end points i. Successful implementation of concurrent non-pharmacologic therapy may permit later reduction in the dose or number of antihypertensive agents. There is no optimal "one size fits all" approach to attain BP control goals, as each approach needs to be tailored to the patient phenotype and genotype.

However, certain objectives and strategies are clear. In almost all cases of advanced CKD, a minimum of two medications will be needed initially.

However, more recent data suggests that addition of a diuretic or CCB as a second agent is appropriate. Properly dosed diuretics are mandatory earlier in the treatment regimen when the patient has evidence of edema or is non-adherent with a low sodium diet. However, achieving the BP goal within 3 - 4 months is more important than the regimen used to achieve this goal. The diuretic chosen should be appropriate for level of eGFR, i.

A general evidence-based approach put forth by an international consensus panel to treat blood pressure in CKD with severely increased proteinuria, and further updated in a position paper by the American Society of Hypertension is shown in Figure 1. The evidence for earlier forms of CKD with low levels of albuminuria or normoalbuminuria should focus on blood pressure control as there is no class of antihypertensive agent that is superior to any other for achieving this goal.

High Blood Pressure and Diabetic Kidney Disease | Joslin Diabetes Center

However, per recent guidelines, ACE inhibitors or angiotensin receptor blockers ARB are the best-tolerated single agents. Current evidence indicates that in type 1 diabetes, ACE inhibitors are recommended as part of a therapeutic regimen to achieve BP goals; similar observations are seen in type 2 diabetes with both classes of RAS inhibitors. Long-term follow-up studies indicate that serum creatinine elevation in this setting actually correlates with slower progression of kidney disease when followed over seven or more years.

This has been observed by multiple investigators and is in the National Kidney Foundation guidelines for treatment of people with advanced kidney disease. Combination therapy is ultimately required in almost all patients with advanced CKD, as the algorithm in Figure 2 suggests. In patients with severely increased albuminuria and hypertension, the clinician's focus should be on treating both. These two events are not necessarily related.

Among patients with advanced proteinuric CKD, current evidence does not support the use of combined blockade of the renin-angiotensin system with both an ACE inhibitor and an angiotensin receptor blocker ARB.

Author’s contributions

Use of aldosterone blockade in advanced proteinuric CKD is particularly useful as it lowers BP more than the other RAS agents in obese patients, either alone or in combination, and provides greater anti-proteinuric effects. This reduction is not solely related to further blood pressure reduction. However, recent prospective randomized trials demonstrate excellent safety and efficacy of new oral non-absorbed potassium.

If albuminuria remains severely increased, the addition of non-dihydropyridine calcium channel blockers CCBs: Moreover, guidelines state that dihydropyridine CCBs should not be used as monotherapy in CKD patients with severely increased albuminuria, but always in combination with an RAS inhibitor. Once triple therapy with an RAS inhibitor, CCB, and appropriately dosed diuretic has been tried and the patient is still not reaching their BP goal, other options include referral to a board certified hypertension specialist http: Findings from the GEMINI trial demonstrate benefits in glycemic control and albuminuria reduction compared to metoprolol.

The antihypertensive effects of conventional beta-blockers, as well as their capability to reduce cardiovascular mortality in high-risk patients are well established, but there is no direct evidence that these agents provide additional renoprotective effects. Moreover, the addition of beta-blockers to further lower BP in the setting of advanced CKD with fully dosed RAS blockers is weak, as noted in the COSMOS study, where only a 3-mmHg additional BP reduction was noted on hour ambulatory monitoring when maximal dose carvedilol was added to maximal dose lisinopril.

Newer beta-blockers with vasodilating properties, such as carvedilol and nebivolol, may reduce mortality in patients on dialysis as noted in cross-sectional studies. Moreover, recent findings demonstrate the majority of negative effects of beta-blockers are relegated to atenolol and not others in the class.

These findings suggest that vasodilator beta-blockers could be used in patients with CKD. Additional agents such as clonidine, guanfacine, minoxidil, nitrates, and hydralazine, may be used, but clonidine is not well tolerated and does not have additive BP lowering effects when used with beta-blockers, while the other agents are very sodium retaining and can actually increase BP if not used appropriately with other medications. Lastly, certain combinations of CCBs, such as diltiazem with long-acting nifedipine or amlodipine, have additive BP-lowering effects and are useful as further or fifth-line agents.

Once patients have established diabetic nephropathy, i. The risk of adverse cardiovascular events in this group of patients is significantly higher than age-matched controls without CKD. As well, if aggressive management of BP and other risk factors does not occur early, disease progression will proceed more rapidly. There is no specific role for nurses in such a setting except for diabetes nurse educators, who are critical for helping the patient understand and manage their blood sugars and who can reinforce the physician's message about achieving other related goals, such as BP reduction.

These professionals are useful to ensure adherence with medication and should work with the clinician to communicate a unified message to the patient. These are perhaps the most underutilized and most important members of the team. They can ensure that the patient understands the importance of low protein and low sodium intake as well as help reinforce their impact on outcomes.

Some patients suffer from depression and a therapist can help with coping of this disease and its consequences. Approaches to glucose and blood pressure management are summarized in this paper. What are the genetics of the kidney disease? Journal of Clinical Hypertension. In Standard of Medical Care in Diabetes — ".

Hypertension Management in Diabetic Kidney Disease

Am J Kidney Dis. Journal of the American Society of Nephrology: N Engl J Med. J Am Soc Nephrol. Predictors of 5-year urinary albumin excretion rate patterns in initially normoalbuminuric patients".

Hypertension n Diabetes in relation to CKD by keluqypanece.tk Khanna

Clin J Am Soc Nephrol.

Kidney and Hypertension in Diabetes Mellitus Kidney and Hypertension in Diabetes Mellitus
Kidney and Hypertension in Diabetes Mellitus Kidney and Hypertension in Diabetes Mellitus
Kidney and Hypertension in Diabetes Mellitus Kidney and Hypertension in Diabetes Mellitus
Kidney and Hypertension in Diabetes Mellitus Kidney and Hypertension in Diabetes Mellitus
Kidney and Hypertension in Diabetes Mellitus Kidney and Hypertension in Diabetes Mellitus
Kidney and Hypertension in Diabetes Mellitus Kidney and Hypertension in Diabetes Mellitus
Kidney and Hypertension in Diabetes Mellitus Kidney and Hypertension in Diabetes Mellitus
Kidney and Hypertension in Diabetes Mellitus Kidney and Hypertension in Diabetes Mellitus

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