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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: Jul 2015. | This topic last updated: Aug 26, 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" and "Overview of kidney disease in HIV-positive patients" and "Primary care of the HIV-infected adult".)

DIALYSIS

Trends in permanent arteriovenous fistula usage at hemodialysis initiation (June 2015)

Excessive numbers of patients continue to initiate hemodialysis with catheters in spite of the 1997 National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (K-DOQI) recommendations that primary arteriovenous (AV) fistula be constructed in at least 50 percent of all new patients electing to receive hemodialysis as their initial form of renal replacement therapy (Fistula first). A review of the United States Renal Data System identified 510,000 patients, of whom 83 percent initiated hemodialysis with a catheter, 14 percent with an AV fistula, and 3.4 percent with an AV graft [5]. Functioning permanent access at initiation of hemodialysis was associated with lower mortality rates compared with those initiating hemodialysis with a catheter, including patients using a temporary catheter while awaiting maturation of an AV access. (See "Arteriovenous fistulas and grafts for chronic hemodialysis access", section on 'Recommended strategy for chronic hemodialysis access'.)

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 [6]. 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) [7]. 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'.)

HYPERTENSION

Chlorthalidone and indapamide for hypertension treatment (July 2015)

Two meta-analyses compared thiazide-like diuretics (chlorthalidone and indapamide) with hydrochlorothiazide for the treatment of hypertension.

In a meta-analysis of 14 trials that compared the blood pressure reduction with one of three dose levels of hydrochlorothiazide (low, intermediate, high) to a corresponding dose level of one of the thiazide-like diuretics, systolic pressure reduction was greater with chlorthalidone and indapamide (by 3.6 and 5.1 mmHg, respectively) [8].

In a multiple-treatment (network) meta-analysis of 21 trials that indirectly compared thiazide-type diuretics (such as hydrochlorothiazide) with thiazide-like diuretics (such as chlorthalidone) by evaluating their efficacy against placebo or common comparator drugs, thiazide-like diuretics significantly lowered the relative risk of cardiovascular events by 12 percent and heart failure by 21 percent [9].

If a diuretic is chosen for treatment of hypertension, we suggest chlorthalidone or indapamide rather than hydrochlorothiazide.

(See "Choice of drug therapy in primary (essential) hypertension: Recommendations", section on 'Thiazide-like versus thiazide-type diuretics'.)

Renal denervation in patients with resistant hypertension (July 2015)

An open-label randomized trial (DENERHTN) compared stepped antihypertensive therapy alone with stepped antihypertensive therapy plus renal denervation in 106 patients with confirmed resistant hypertension despite therapy with indapamide, amlodipine, and ramipril (or irbesartan if allergic to angiotensin converting [ACE] enzyme inhibitors) [10]. Stepped antihypertensive therapy consisted of spironolactone, bisoprolol, prazosin, and rilmenidine added (in that order) at monthly intervals as needed. At six months, the change in 24-hour ambulatory systolic pressure decreased significantly more in the denervation group (-15.4 versus -9.5 mmHg). However, there was no sham intervention, and the baseline blood pressure was higher in the denervation group, suggesting that the results could be due in part to regression to the mean. Given the negative findings from SYMPLICITY-HTN-3 (a blinded trial), further studies are needed before renal denervation can be widely recommended for resistant hypertension. (See "Treatment of resistant hypertension", section on 'Catheter-based radiofrequency ablation of renal sympathetic nerves'.)

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 [11]. 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 [12]. 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 [13]. 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 [14]. 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 [15]. 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'.)

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 [16]. 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'.)

TRANSPLANTATION

Retrieval of kidneys under hypothermic versus normothermic conditions (August 2015)

The standard protocol for management of deceased-donor kidneys mandates that retrieval of organs be done under normothermic conditions. Therapeutic hypothermia (or targeted temperature management) may decrease the risk of delayed graft function. This was shown in a study in which 370 organ donors (resulting in 572 kidney transplants) were randomly assigned after declaration of brain death to organ retrieval under normothermic or hypothermic conditions [17]. Delayed graft function occurred less frequently in the hypothermic compared with the normothermic group, even after adjusting for donor type, creatinine, and age; kidney cold ischemia time; and organ procurement agency. The long-term effects of hypothermia on graft survival or acute rejection were not tested by this trial. However, these data suggest an inexpensive and safe intervention that may increase graft survival. (See "Deceased and living donor renal allograft recovery", section on 'Therapeutic hypothermia'.)

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 [18]. 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

Long-term patiromer therapy for hyperkalemia in chronic kidney disease (July 2015)

Patiromer is an investigational agent that appears promising for long-term control of hyperkalemia in patients with chronic kidney disease. It is a spherical, nonabsorbable organic polymer, formulated as a powder for suspension, which binds potassium in the colon in exchange for calcium. In a phase II, open-label dose-finding trial (AMETHYST-DN), 306 diabetic patients with an estimated glomerular filtration rate (eGFR) of 15 to 59 mL/min/1.73 m2 and either mild or moderate hyperkalemia were randomly assigned to a range of initial patiromer doses [19]. At four weeks, the change in serum potassium from baseline ranged from -0.35 mEq/L with a dose of 4.2 g twice daily to -0.97 mEq/L with a dose of 12.6 g twice daily. At 52 weeks, serum potassium concentrations remained in the normal range with continued patiromer therapy. Discontinuation of patiromer resulted in an increase in the serum potassium within three days. The most common treatment-related side effects included constipation and hypomagnesemia. Severe hypomagnesemia (a serum magnesium <1.2 mg/dL) developed in 13 patients. (See "Treatment and prevention of hyperkalemia in adults", section on 'Patiromer'.)

International consensus on management of IgG4-related disease (July 2015)

The optimal treatment for immunoglobulin G4-related disease (IgG4-RD) has not been established, nor have randomized trials been performed to inform treatment approaches. Nonetheless, broad international consensus has been achieved among experts on several major management strategies [20]. These include the importance of biopsy confirmation of the diagnosis to exclude malignancy and other disorders that may mimic IgG4-RD; the need to treat symptomatic patients, sometimes urgently, as well as some asymptomatic patients; use of glucocorticoids as first-line therapy; use of maintenance therapy in certain patients; and retreatment strategies for patients who relapse after successful remission induction. Consensus was not reached on the use of steroid-sparing immunosuppressive agents from the start of treatment, and largely reflects different practice styles between countries. (See "Overview of IgG4-related disease", section on 'Diagnostic studies' and "Overview of IgG4-related disease", section on 'Treatment principles and observations'.)

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'.)

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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. Malas MB, Canner JK, Hicks CW, et al. Trends in incident hemodialysis access and mortality. JAMA Surg 2015; 150:441.
  6. 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.
  7. 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.
  8. Roush GC, Ernst ME, Kostis JB, et al. Head-to-head comparisons of hydrochlorothiazide with indapamide and chlorthalidone: antihypertensive and metabolic effects. Hypertension 2015; 65:1041.
  9. Olde Engberink RH, Frenkel WJ, van den Bogaard B, et al. Effects of thiazide-type and thiazide-like diuretics on cardiovascular events and mortality: systematic review and meta-analysis. Hypertension 2015; 65:1033.
  10. Azizi M, Sapoval M, Gosse P, et al. Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial. Lancet 2015; 385:1957.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. Pickard R, Starr K, MacLennan G, et al. Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial. Lancet 2015; 386:341.
  17. Niemann CU, Feiner J, Swain S, et al. Therapeutic Hypothermia in Deceased Organ Donors and Kidney-Graft Function. N Engl J Med 2015; 373:405.
  18. 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.
  19. Bakris GL, Pitt B, Weir MR, et al. Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease: The AMETHYST-DN Randomized Clinical Trial. JAMA 2015; 314:151.
  20. Khosroshahi A, Wallace ZS, Crowe JL, et al. International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease. Arthritis Rheumatol 2015; 67:1688.
  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.
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