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What's new in nephrology and hypertension
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What's new in nephrology and hypertension

Disclosures: Alice M Sheridan, MD Nothing to disclose. John P Forman, MD, MSc Nothing to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2015. | This topic last updated: Jun 25, 2015.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

ACUTE AND CHRONIC KIDNEY DISEASE

Remote ischemic preconditioning protects against ischemic acute kidney injury (June 2015)

Remote ischemic preconditioning (RIPC) is a method by which the induction of transient ischemia of an organ (usually an upper arm) protects against subsequent ischemic injury of another organ. A randomized trial including 240 patients has suggested a protective benefit of RIPC on the incidence of acute kidney injury (AKI) [1]. Increases in urinary biomarkers following RIPC were associated with reduced AKI in this trial. The benefit of RIPC on renal outcomes, morbidity, and mortality needs to be studied in other multicenter trials before it is used clinically. The safety of repeated episodes of transient ischemia has not been conclusively demonstrated. (See "Possible prevention and therapy of postischemic (ischemic) acute tubular necrosis", section on 'Remote ischemic preconditioning'.)

Diagnostic criteria for hepatorenal syndrome (April 2015)

The International Club of Ascites has altered their diagnostic criteria for hepatorenal syndrome [2]. The new criteria recognize that, in such patients, acute kidney injury can sometimes be characterized by small absolute increases in serum creatinine. (See "Hepatorenal syndrome", section on 'Diagnosis'.)

Resolution of hepatorenal syndrome after liver transplantation (March 2015)

Resolution of type 1 hepatorenal syndrome was examined in 62 patients undergoing liver transplantation at a single center over a 10 year period [3]. Of these, resolution of hepatorenal syndrome occurred in 47 patients (76 percent). The remaining patients either died or required long-term dialysis. The mean duration of dialysis prior to liver transplantation was the only significant predictor of resolution (10 days among those who resolved versus 25 days among those who did not). (See "Hepatorenal syndrome", section on 'Improving hepatic function'.)

HIV infection and chronic kidney disease (February 2015)

The HIV Medicine Association of the Infectious Diseases Society of America has updated its guidelines for the management of chronic kidney disease in patients infected with HIV [4]. They recommend screening for kidney disease with serum creatinine measurement and urinalysis at baseline and during use of antiretroviral therapy. The guidelines also discuss indications for nephrology referral and selection of antiretroviral regimens in the setting of renal impairment. The discussion in UpToDate is generally consistent with these guidelines. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient", section on 'Tenofovir-emtricitabine' and "Overview of kidney disease in HIV-positive patients" and "Primary care of the HIV-infected adult".)

DIALYSIS

Cinacalcet and calciphylaxis in hemodialysis patients (June 2015)

Calciphylaxis (calcific uremic arteriolopathy, CUA) is a serious disorder that afflicts hemodialysis patients and is characterized by systemic medial calcification of arterioles resulting in ischemia and subcutaneous necrosis. An analysis of adverse event reports collected during the Evaluation of Cinacalcet (EVOLVE) trial suggested that the use of cinacalcet may reduce the risk of calciphylaxis [5]. However, our confidence in these results is limited, due to a high drop-out rate in the cinacalcet group and a high rate of crossover in the placebo group: nearly 20 percent of patients in the placebo group ended up taking commercially available cinacalcet. Additionally, although cinacalcet reduced the risk of hyperparathyroidism, the decrease in the risk of CUA appears to have been unrelated to cinacalcet's effect on parathyroid hormone (PTH). Further study is needed before providing recommendations regarding the use of cinacalcet to prevent calciphylaxis in high-risk individuals. (See "Calciphylaxis (calcific uremic arteriolopathy)", section on 'Epidemiology and risk factors' and "Management of secondary hyperparathyroidism and mineral metabolism abnormalities in dialysis patients", section on 'Efficacy studies'.)

Drug-eluting balloon angioplasty for hemodialysis arteriovenous access stenosis (March 2015)

Drug-eluting balloons (DEB) have been used in angioplasty with the aim of preventing restenosis due to neointimal hyperplasia, which is a major concern. Outcomes using DEBs for the treatment of stenotic hemodialysis arteriovenous (AV) access lesions have been mixed and not as favorable as with coronary or peripheral arterial lesions. In a small trial of 40 patients with hemodialysis AV access stenosis, the cumulative primary patency at one year was higher following DEB (paclitaxel) angioplasty compared with plain balloon angioplasty (7 of 20 versus 1 of 20 patients) [6]. Primary patency was greater with DEB for AV grafts (AVG), but the difference in patency rates for AV fistulas (AVF) was not statistically significant. Larger trials are warranted to confirm the observed benefit and to further evaluate possible differences between the response of AVGs versus AVFs. (See "Percutaneous angioplasty for the treatment of venous stenosis affecting hemodialysis access grafts", section on 'Drug-eluting balloon'.)

GLOMERULAR DISEASE AND VASCULITIS

Rapid test for complement-mediated thrombotic microangiopathy (April 2015)

Primary thrombotic microangiopathies (TMAs) are rare, potentially life-threatening conditions that cause microangiopathic hemolytic anemia, thrombocytopenia, and variable degrees of renal failure and other organ damage. A critical assessment must be made between thrombotic thrombocytopenic purpura (TTP) and complement-mediated TMA, because appropriate therapy for TTP involves urgent plasma exchange, and therapy for complement-mediated TMA involves the therapeutic antibody eculizumab. Both of these therapies are costly and have significant toxicities, and generally they cannot be given concurrently. A rapid test using complement-sensitive cells has been developed, and in a small cohort of adult patients with known diagnoses of TTP or complement-mediated TMA, this testing was effective in correctly identifying the diagnosis [7]. Further study is required to establish the usefulness of this testing in the evaluation of patients with a suspected TMA. (See "Diagnosis of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults", section on 'Evaluation'.)

HYPERTENSION

Mortality in frail older adults taking combination antihypertensive therapy (May 2015)

In a cohort of 1127 frail nursing home residents from France and Italy (aged 80 years and older), the two-year mortality rate (32 percent) was highest among those who were treated with two or more antihypertensive drugs and had a systolic pressure less than 130 mmHg [8]. Mortality was lower (about 20 percent) among individuals who had higher blood pressures despite taking two or more antihypertensive drugs, and among those taking fewer medications regardless of blood pressure. Increased mortality for those who had a systolic pressure less than 130 mmHg while being treated with two or more drugs may have been due to a higher prevalence in this group of heart failure (35 versus 14 percent) and coronary heart disease (35 versus 18 percent). (See "Treatment of hypertension in the elderly patient, particularly isolated systolic hypertension", section on 'Problem of frailty'.)

Iliac arteriovenous anastomosis for resistant hypertension (April 2015)

Creation of an arteriovenous anastomosis between large vessels shunts a substantial amount of blood into the high-capacity, low-resistance venous system, which can decrease total systemic vascular resistance and therefore decrease blood pressure. This approach was examined in an open-label trial of 83 adults with resistant hypertension [9]. At six months, percutaneous placement of an iliac arteriovenous anastomosis significantly lowered office systolic pressure (27 versus 4 mmHg) and 24-hour ambulatory systolic pressure (14 versus 1 mmHg) compared with usual care. Venous stenosis presenting as unilateral lower extremity edema occurred in 12 patients (29 percent) who underwent the anastomosis; 13 other adverse events occurred in the treatment group, including one iliac artery dissection and one deep venous thrombosis. The effects on cardiac output and central hemodynamics, as well as the long-term safety of the procedure, were not assessed. Blinded studies (eg, using a sham control) with longer follow-up are required before iliac arteriovenous anastomosis can be recommended to treat patients with resistant hypertension. (See "Treatment of resistant hypertension", section on 'Central arteriovenous anastomosis'.)

Chronic hypertension may increase risk of congenital anomalies (March 2015)

Children of women with chronic hypertension, either treated or untreated, appear to be at increased risk of congenital malformations, particularly cardiac malformations. In a recent study, the risk of congenital heart disease was increased by 50 percent in offspring of women with untreated hypertension compared with offspring of normotensive controls, which corresponds to 1.4 additional cases of congenital heart disease per 100 pregnancies in women with hypertension [10]. This suggests that factors associated with hypertension or hypertension itself increases the risk for congenital malformations independent of antihypertensive drug therapy. (See "Management of hypertension in pregnant and postpartum women", section on 'Antihypertensive therapy'.)

Long-term effect of antihypertensive therapy in diabetic patients (October 2014, MODIFIED March 2015)

A randomized trial and a meta-analysis have evaluated the treatment of hypertension in patients with diabetes.

The ADVANCE trial randomly assigned 11,000 diabetic patients to a fixed combination of perindopril-indapamide or placebo for approximately four years. Patients in the perindopril-indapamide group had lower rates of cardiovascular mortality (3.8 versus 4.6 percent) and all-cause mortality (7.3 versus 8.5 percent). A post-trial, open-label cohort (8500 patients) were followed for an additional six years [11]. Blood pressures between the treatment and placebo groups, which were different during the trial (135/74 versus 140/76 mmHg), became similar within six months of the trial completion and remained similar throughout the cohort phase. Compared with those originally assigned placebo, those who had received perindopril-indapamide had a lower death rate during the cohort phase (15.3 versus 16.7 percent), as well as a lower incidence of major cardiovascular events (13.3 versus 14.2 percent). Combining both the trial and cohort phases together (approximately 10 years of follow-up), all-cause mortality was lower among those in the treatment group. Thus, blood pressure lowering is associated with long-term benefits on mortality and cardiovascular disease in diabetic patients. (See "Treatment of hypertension in patients with diabetes mellitus", section on 'ADVANCE trial'.)

A meta-analysis of 40 trials examined the effect of antihypertensive therapy in 100,354 diabetic patients [12]. Follow-up ranged from six months to more than eight years, with most trials following patients for two years or longer. Compared with placebo, antihypertensive therapy reduced the rates of mortality, total cardiovascular disease, myocardial infarction, and stroke. For most outcomes, the benefit of antihypertensive therapy was limited to those whose initial systolic pressures were greater than 140 mmHg. The risk of stroke, but not other outcomes, was reduced by antihypertensive therapy in patients with lower initial systolic pressures. Some trials compared one antihypertensive drug with another. For most outcomes, no class of drugs was superior or inferior to the others. However, beta-blockers increased the risk of stroke compared with other agents. In general, the results of this meta-analysis support recommendations by UpToDate regarding the treatment of hypertension in diabetic patients. (See "Treatment of hypertension in patients with diabetes mellitus", section on 'Meta-analysis'.)

Target diastolic blood pressure in pregnancy (February 2015)

In pregnant women with chronic (preexistent) or gestational hypertension, the effect of less-tight versus tight control of hypertension on pregnancy complications is unclear. A randomized trial that assigned pregnant women with gestational or chronic hypertension to diastolic blood pressure treatment targets of 85 or 100 mmHg reported similar maternal, fetal, and neonatal outcomes in both groups [13]. More women in the 100 mmHg target group developed severe hypertension, although this was not associated with an increase in transient ischemic attack or stroke. The trial was not powered to exclude a clinically important increase in fetal growth restriction in the 85 mmHg target group. For these reasons, we continue to suggest a diastolic pressure target of 90 to 100 mmHg for pregnant women with hypertension without end-organ damage. (See "Management of hypertension in pregnant and postpartum women", section on 'Blood pressure goal'.)

Antihypertensive therapy provides benefit in mild hypertension (January 2015)

The benefit of antihypertensive drug therapy has been questioned in patients with mild hypertension (systolic 140 to 159 mmHg and/or diastolic 90 to 99 mmHg) and no preexisting cardiovascular disease. A meta-analysis including 15,266 such patients reported that, compared with placebo or a less intensive regimen, antihypertensive therapy or a more intensive regimen for five years produced significantly lower rates of all-cause mortality (3.9 versus 4.8 percent) and stroke (1.6 versus 2.1 percent), and similar rates of myocardial infarction [14]. Thus, low-risk patients with mild hypertension and no preexisting cardiovascular disease who fail to reduce their blood pressure with lifestyle modification should receive antihypertensive therapy. (See "Hypertension: Who should be treated?", section on 'Low-risk patients'.)

NEPHROLITHIASIS

Tamsulosin or nifedipine for acute nephrolithiasis (May 2015)

Meta-analyses of randomized trials have found that therapy with an alpha blocker or calcium channel blocker ("medical expulsive therapy" or MET) in patients with small ureteral calculi increases both the likelihood and speed of stone passage. A subsequent trial randomly assigned 1167 adult patients presenting with ureteric colic caused by small stones (10 mm or less) to four weeks of therapy with tamsulosin, nifedipine, or placebo [15]. The primary endpoint, which was the need for further intervention (such as lithotripsy) within four weeks, and all secondary endpoints (including days until stone passage and pain), were assessed by self-administered questionnaires at four weeks; follow-up imaging was not routinely performed. There was no benefit from tamsulosin or nifedipine for any endpoint. However, patients with small stones infrequently require intervention, and self-reported stone passage is likely to be inaccurate. These concerns seriously limit the usefulness of this trial. For patients with stones ≤10 mm in diameter, we consider MET an option to facilitate spontaneous stone passage. (See "Diagnosis and acute management of suspected nephrolithiasis in adults", section on 'Facilitating stone passage'.)

PEDIATRIC NEPHROLOGY

Duration of initial steroid therapy in children with idiopathic nephrotic syndrome (January 2015)

Children with idiopathic nephrotic syndrome (NS) are usually responsive to an initial empirical course of corticosteroid therapy. However, the optimal duration of initial therapy to reduce the risk and frequency of subsequent relapses remains uncertain. Previous systematic reviews showed that initial prednisone therapy of at least three to seven months, compared to shorter courses, reduced the risk of relapses. But, two recent randomized trials report prolonged initial prednisolone therapy (six months) did not reduce the frequency of later relapses compared to shorter course (two to three months) [16,17]. Of note, there are no trials that directly compare prednisone and prednisolone as first-line treatment for NS, and it is unknown whether the dosing used for these studies was equivalent. Our current approach, when corticosteroid therapy is initiated to treat children with NS, is to administer therapy for at least two to three months. (See "Treatment of idiopathic nephrotic syndrome in children", section on 'Length of therapy and risk of relapse'.)

Genetic testing for sporadic steroid-resistant nephrotic syndrome (January 2015)

Genetic testing may be useful in children with sporadic steroid-resistant nephrotic syndrome (SRNS) who do not have a family history of SRNS or evidence of syndromic nephrotic syndrome due to a genetic mutation (eg, Denys-Drash syndrome and WT1 mutation). This was illustrated in two studies that reported that a third of patients with sporadic SRNS were identified as having a genetic condition associated with SRNS that is not responsive to immunosuppressive therapy [18,19]. As a result, we suggest genetic testing in patients who do not respond to steroid therapy and in whom renal biopsy findings are consistent with a diagnosis of idiopathic NS (eg, minimal change disease or focal segmental glomerulosclerosis). Genetic screening for this selective group of patients who have a high likelihood of a genetic condition would avoid unnecessary exposure to other immunosuppressive agents for those with an underlying genetic condition. (See "Steroid-resistant idiopathic nephrotic syndrome in children", section on 'Genetic testing'.)

TRANSPLANTATION

Kidney transplantation from HIV-positive deceased donors into HIV-positive recipients (February 2015)

As is the case for most other patients with end stage renal disease (ESRD), kidney transplantation is superior to other forms of renal replacement therapy for HIV-positive patients with ESRD. In countries where dialysis is a limited resource, kidney transplantation is life-saving. However, kidney transplantation is limited by a shortage of available organs. In a case series from South Africa, 27 carefully selected and treated HIV-positive patients underwent transplantation with kidneys from HIV-positive deceased donors [20]. Patient and allograft survival at 1, 3 and 5 years was comparable to reported patient and allograft survival of HIV-positive patients who received kidneys from HIV-negative donors. (See "Solid organ transplantation in HIV-infected individuals", section on 'Renal transplantation'.)

OTHER NEPHROLOGY

Combination renin-angiotensin system inhibition in diabetic patients (June 2015)

Several randomized trials that directly compared dual versus single renin-angiotensin system inhibition in diabetic patients found that dual therapy produced no benefit and an increase in adverse effects. Findings are similar in a subsequent network meta-analysis [21]. In this analysis in patients with diabetes and hypertension, dual therapy with an angiotensin-converting enzyme (ACE) inhibitor plus an angiotensin II receptor blocker (ARB) was superior to placebo in preventing end-stage renal disease, but monotherapy with either an ACE inhibitor or an ARB, also compared with placebo, produced similar benefits while dual therapy produced more adverse effects. Combination renin-angiotensin system inhibition with an ACE inhibitor and ARB or direct renin inhibitor is not recommended in diabetic patients. (See "Treatment of hypertension in patients with diabetes mellitus", section on 'Avoid combination renin-angiotensin system inhibition'.)

Icatibant for ACE-inhibitor associated angioedema (February 2015)

Angiotensin-converting enzyme (ACE) inhibitors cause episodic, bradykinin-mediated angioedema in less than 1 percent of recipients, but this accounts for approximately one-third of angioedema cases presenting to emergency departments in countries where these medicines are widely used. The most common approach to management of severe episodes affecting the airway has been discontinuation of the ACE inhibitors and supportive care, which may involve intubation and even tracheotomy. Icatibant, a bradykinin receptor antagonist approved for use in hereditary angioedema, has now been shown to be effective for ACE inhibitor-associated angioedema [22]. In a randomized trial of 27 adults presenting to the emergency department with angioedema of the upper aerodigestive tract while taking an ACE inhibitor, patients received one dose of icatibant or standard therapy (an intravenous glucocorticoid plus an antihistamine). Symptoms in the icatibant group resolved in a median of 8 hours, compared with 27 hours in the glucocorticoid/antihistamine group, and icatibant was well tolerated. Icatibant is most likely to be effective if given in the first few hours of an angioedema attack when the swelling is still increasing. (See "ACE inhibitor-induced angioedema", section on 'Icatibant'.)

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REFERENCES

  1. Zarbock A, Schmidt C, Van Aken H, et al. Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial. JAMA 2015; 313:2133.
  2. Angeli P, Ginès P, Wong F, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol 2015; 62:968.
  3. Wong F, Leung W, Al Beshir M, et al. Outcomes of patients with cirrhosis and hepatorenal syndrome type 1 treated with liver transplantation. Liver Transpl 2015; 21:300.
  4. Lucas GM, Ross MJ, Stock PG, et al. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2014; 59:e96.
  5. Floege J, Kubo Y, Floege A, et al. The Effect of Cinacalcet on Calcific Uremic Arteriolopathy Events in Patients Receiving Hemodialysis: The EVOLVE Trial. Clin J Am Soc Nephrol 2015; 10:800.
  6. Kitrou PM, Katsanos K, Spiliopoulos S, et al. Drug-eluting versus plain balloon angioplasty for the treatment of failing dialysis access: final results and cost-effectiveness analysis from a prospective randomized controlled trial (NCT01174472). Eur J Radiol 2015; 84:418.
  7. Gavriilaki E, Yuan X, Ye Z, et al. Modified Ham test for atypical hemolytic uremic syndrome. Blood 2015; 125:3637.
  8. Benetos A, Labat C, Rossignol P, et al. Treatment With Multiple Blood Pressure Medications, Achieved Blood Pressure, and Mortality in Older Nursing Home Residents: The PARTAGE Study. JAMA Intern Med 2015; 175:989.
  9. Lobo MD, Sobotka PA, Stanton A, et al. Central arteriovenous anastomosis for the treatment of patients with uncontrolled hypertension (the ROX CONTROL HTN study): a randomised controlled trial. Lancet 2015; 385:1634.
  10. Bateman BT, Huybrechts KF, Fischer MA, et al. Chronic hypertension in pregnancy and the risk of congenital malformations: a cohort study. Am J Obstet Gynecol 2015; 212:337.e1.
  11. Zoungas S, Chalmers J, Neal B, et al. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl J Med 2014; 371:1392.
  12. Emdin CA, Rahimi K, Neal B, et al. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA 2015; 313:603.
  13. Magee LA, von Dadelszen P, Rey E, et al. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med 2015; 372:407.
  14. Sundström J, Arima H, Jackson R, et al. Effects of blood pressure reduction in mild hypertension: a systematic review and meta-analysis. Ann Intern Med 2015; 162:184.
  15. Pickard R, Starr K, MacLennan G, et al. Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial. Lancet 2015.
  16. Sinha A, Saha A, Kumar M, et al. Extending initial prednisolone treatment in a randomized control trial from 3 to 6 months did not significantly influence the course of illness in children with steroid-sensitive nephrotic syndrome. Kidney Int 2015; 87:217.
  17. Yoshikawa N, Nakanishi K, Sako M, et al. A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment. Kidney Int 2015; 87:225.
  18. Giglio S, Provenzano A, Mazzinghi B, et al. Heterogeneous genetic alterations in sporadic nephrotic syndrome associate with resistance to immunosuppression. J Am Soc Nephrol 2015; 26:230.
  19. Sadowski CE, Lovric S, Ashraf S, et al. A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol 2015; 26:1279.
  20. Muller E, Barday Z, Mendelson M, Kahn D. HIV-positive-to-HIV-positive kidney transplantation--results at 3 to 5 years. N Engl J Med 2015; 372:613.
  21. Palmer SC, Mavridis D, Navarese E, et al. Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis. Lancet 2015; 385:2047.
  22. Baş M, Greve J, Stelter K, et al. A randomized trial of icatibant in ACE-inhibitor-induced angioedema. N Engl J Med 2015; 372:418.
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