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.
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
Diagnostic criteria for hepatorenal syndrome (April 2015)
The International Club of Ascites has altered their diagnostic criteria for hepatorenal syndrome . 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 . 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 . 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".)
Combination ACE inhibitor plus ARB no benefit in autosomal dominant polycystic kidney disease (November 2014)
Combination therapy with an angiotensin converting enzyme (ACE) inhibitor and an angiotensin receptor blocker (ARB) provides no benefit to patients with many forms of chronic kidney disease, but this has not been shown among patients with autosomal dominant polycystic kidney disease (ADPKD). Lisinopril plus placebo was compared with lisinopril plus telmisartan in a large randomized trial of ADPKD patients with reduced estimated glomerular filtration rate (eGFR) . There was no difference between groups in the composite endpoint of death, end-stage renal disease, or 50 percent reduction in estimated GFR. (See "Hypertension in autosomal dominant polycystic kidney disease", section on 'Angiotensin-converting enzyme inhibitor plus angiotensin receptor antagonist'.)
Blood pressure target in autosomal dominant polycystic kidney disease (November 2014)
The optimal blood pressure target for patients with autosomal dominant polycystic kidney disease (ADPKD) is not known. A low blood pressure target (defined as <95/60 to 110/75 mmHg) was compared with a standard blood pressure target (defined as 120/70 to 130/80 mmHg) in a large randomized trial . Patients in the low blood pressure target group had a lower rate of increase in total kidney size. However, side effects including lightheadedness and dizziness were more common in the low target group. (See "Hypertension in autosomal dominant polycystic kidney disease", section on 'Blood pressure goal'.)
Long-term effect of intensive glycemic control on macrovascular outcomes in type 2 diabetes (October 2014)
The ADVANCE trial randomly assigned 11,140 patients with long-standing type 2 diabetes to either standard therapy or modified release gliclazide plus other drugs as required to achieve an A1C of <6.5 percent, and found no benefit of intensive therapy on the primary composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke after a median of five years. Of the 10,082 surviving trial participants, 8494 enrolled in a post-trial monitoring study . A 2000-patient random subset of the surviving cohort that agreed to participate in the post-trial monitoring study had periodic laboratory testing for A1C, fasting blood glucose, serum creatinine, blood pressure, and weight. Mean A1C, which had been significantly different during the trial, became similar by the first post-trial visit and remained similar throughout the monitoring period (7.2 and 7.4 percent in the original intensive and standard groups, respectively). After a median total follow-up of 9.9 years, similar to the findings in the randomized trial, there was no benefit of intensive therapy on macrovascular outcomes. (See "Glycemic control and vascular complications in type 2 diabetes mellitus", section on 'ADVANCE'.)
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) . 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
THSD7A as a novel antigen in idiopathic membranous nephropathy (November 2014)
Approximately 70 to 80 percent of patients with primary (idiopathic) membranous nephropathy (MN) have a positive test for anti-phospholipase A2 receptor (PLA2R) antibodies. Thrombospondin type-1 domain-containing 7A (THSD7A) is, like PLA2R, a transmembrane protein expressed on podocytes. THSD7A may be the responsible antigen in approximately 10 percent of patients with idiopathic MN who are negative for anti-PLA2R antibodies. The association of THSD7A with membranous nephropathy was examined in a study of 154 patients with anti-PLA2R-negative idiopathic MN, 74 patients with anti-PLA2R-positive idiopathic MN, 76 patients with other glomerular disease, and 44 healthy controls . Autoantibodies specific for THSD7A were identified in sera from 15 of 154 patients with anti-PLA2R-negative idiopathic MN, but not in the sera from other individuals. (See "Causes and diagnosis of membranous nephropathy", section on 'Thrombospondin type-1 domain-containing 7A'.)
Rituximab as maintenance therapy in ANCA-associated vasculitis (November 2014)
Azathioprine and methotrexate are conventionally considered the preferred drugs for maintenance therapy in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). The Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis (MAINRITSAN) trial compared rituximab with azathioprine as maintenance therapy in 115 patients who had achieved remission after induction therapy with cyclophosphamide and glucocorticoids . Major relapse rates at 28 months were lower for rituximab (5 versus 29 percent). Rates of adverse events were also similar. However, the dosing of azathioprine in this trial was not consistent with the practice of many experts, and this may have contributed to the excess relapse rate. In addition, most patients had GPA, a positive PR3-ANCA, and were newly diagnosed rather than relapsed patients. It is not clear whether or not these data apply to other groups of patients with ANCA-associated vasculitis or to patients induced with rituximab rather than cyclophosphamide. Thus, either rituximab or azathioprine (or methotrexate although it was not evaluated in this trial) can be used as maintenance therapy in patients with GPA or MPA while awaiting further data to confirm these findings. (See "Maintenance immunosuppressive therapy in granulomatosis with polyangiitis and microscopic polyangiitis", section on 'Rituximab'.)
Abatacept in patients with proliferative lupus nephritis (November 2014)
CTLA4-Ig (abatacept) is a fusion protein that competitively inhibits CD28-B7 T cell costimulation. In the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study (ACCESS), 134 patients with proliferative lupus nephritis (half also had membranous lupus) were treated with cyclophosphamide and glucocorticoids and were randomly assigned to also receive abatacept or placebo . All patients received azathioprine after the conclusion of cyclophosphamide until week 24. The complete response rate at 24 weeks was 33 percent with abatacept and 31 percent with placebo. The total response rate at 24 weeks (complete or partial) was 59 percent in both groups. At one year, 64 percent of patients in the abatacept group and 68 percent in the placebo group had a complete or partial response. Adverse events were similar between the two groups. Thus, these data do not support the use of abatacept in the initial treatment of proliferative lupus nephritis. (See "Therapy of diffuse or focal proliferative lupus nephritis", section on 'Costimulatory blockade with CTLA4-Ig'.)
Combination tacrolimus and mycophenolate mofetil in patients with lupus nephritis (November 2014)
Cyclophosphamide or mycophenolate mofetil, in combination with glucocorticoids, are the preferred agents for initial therapy in patients with focal or diffuse proliferative lupus nephritis (LN). A "multitarget" regimen that combined tacrolimus, low-dose mycophenolate mofetil, and prednisone was compared with high-dose cyclophosphamide and prednisone in 368 Chinese patients with LN . At 24 weeks, the rate of complete response, defined as 24-hour urine protein excretion of 0.4 g or less, serum albumin of 3.5 g/dL or more, normal serum creatinine, and absence of an active urine sediment, was greater in the multitarget group (46 versus 26 percent) as was the overall response rate (complete or partial response; 84 versus 63 percent). Serious adverse events, particularly infections, were more common with multitarget therapy (7 versus 3 percent), as was dropout due to adverse events (6 versus 2 percent). The study was limited by the lack of long-term follow-up of kidney function and by the fact that tacrolimus can reduce proteinuria through a hemodynamic mechanism (which may be unrelated to immunologic recovery). Since all of the patients in this trial had a normal serum creatinine at baseline, proteinuria reduction without immunological recovery could have been classified as a response. Pending further data, we do not advise this multitarget regimen as induction therapy for most patients with proliferative lupus nephritis. (See "Therapy of diffuse or focal proliferative lupus nephritis", section on 'Tacrolimus'.)
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 . 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 . 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 . 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 . 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 . 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'.)
Cardiovascular risk and benefit of antihypertensive therapy (October 2014)
Although the severity of hypertension or magnitude of cardiovascular risk do not affect the relative risk reduction of major cardiovascular events with antihypertensive therapy, the absolute benefit of antihypertensive therapy is greater in patients with more severe hypertension or greater overall cardiovascular risk. In a meta-analysis of 11 randomized trials comparing antihypertensive therapy with placebo, patients were risk-stratified according to their estimated five-year risk of having a major cardiovascular event . In patients with the highest overall cardiovascular risk (ie, five-year risk >21 percent), the absolute risk reduction was 3.8 percent (number needed to treat, 26 patients for five years). In patients with the lowest overall cardiovascular risk (ie, five-year risk approximately 6 percent), the absolute risk reduction was 1.4 percent (number needed to treat, 71 patients for five years). (See "What is goal blood pressure in the treatment of hypertension?", section on 'Benefit according to overall cardiovascular risk'.)
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) [17,18]. 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 [19,20]. 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'.)
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 . 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'.)
Sirolimus and mortality in kidney transplant recipients (December 2014)
The mechanistic target of rapamycin (mTOR) inhibitor, sirolimus, is commonly used for immunosuppression among transplant recipients, and may be associated with a decreased risk of malignancy. A systematic review and meta-analysis of randomized trials demonstrated a decreased risk of malignancy but an increased risk of death associated with sirolimus among kidney and kidney pancreas transplant recipients . (See "Mechanistic target of rapamycin (mTOR) inhibitors in renal transplantation", section on 'Mortality'.)
Levofloxacin does not decrease BK virus infection in kidney transplant recipients (December 2014)
BK virus infection causes allograft failure in kidney transplant recipients and has few effective therapies. The prophylactic effect of the quinolone antibiotic, levofloxacin, on BK viral infection was studied in a randomized placebo-controlled trial including recipients of kidney allografts transplanted between 2011 and 2013 . Compared with placebo, levofloxacin did not decrease the risk of BK infection, allograft rejection, or patient or allograft survival. (See "Management of BK virus-induced (polyomavirus-induced) nephropathy in kidney transplantation", section on 'Quinolone antibiotics'.)
Risk of gestational hypertension or preeclampsia in kidney donors (November 2014)
The assessment of risk conferred by living kidney donation is critically important in determining the suitability of individual donor candidates. A retrospective cohort study demonstrated an increased risk of gestational hypertension or preeclampsia compared with well-matched nondonors . Women of childbearing age who wish to donate a kidney should be advised of this increased risk. (See "Evaluation of the living kidney donor and risk of donor nephrectomy", section on 'Maternal and fetal outcomes'.)
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 . 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'.)
Trimethoprim-sulfamethoxazole and sudden death (December 2014)
While trimethoprim-sulfamethoxazole (TMP-SMX) has generally been felt to be well tolerated, a case-control study found an association between sudden death, possibly due to hyperkalemia, and prescription of TMP-SMX among older patients who were also receiving an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) .Those who received TMP-SMX had an increased seven-day risk of sudden death compared with those who received amoxicillin (adjusted odds ratio 1.38, 95% CI 1.09-1.76). However, other factors that affected the choice of antibiotic may have confounded these results, and higher quality evidence is needed to determine whether this association is causal. (See "Trimethoprim-sulfamethoxazole: An overview", section on 'Life threatening effects'.)
Patiromer for hyperkalemia in patients with chronic kidney disease (November 2014)
Patiromer is a nonabsorbable organic polymer, formulated as a powder for oral suspension, which binds potassium in the colon in exchange for calcium. In OPAL-HK, a phase III randomized placebo-controlled trial, 243 outpatients with chronic kidney disease and persistent hyperkalemia while receiving a stable dose of an ACE inhibitor or ARB were treated with either 4.2 or 8.4 g of patiromer twice daily for four weeks . The mean decrease in serum potassium was 0.6 and 1.2 meq/L with lower and higher doses, respectively; approximately 75 percent of patients achieved the target serum potassium of 3.8 to 5.0 meq/L. Patients whose baseline serum potassium was 5.5 meq/L or greater and who achieved the target serum potassium during the initial four-week period were randomly assigned to patiromer or placebo for another eight weeks. Serum potassium remained the same in patients continuing patiromer and increased by 0.7 meq/L in those assigned placebo. Serious adverse events were rare. The long-term efficacy and safety of patiromer are unknown, as are the effects in patients with acute hyperkalemia or end-stage renal disease. Patiromer is an investigational drug at this time. (See "Treatment and prevention of hyperkalemia in adults", section on 'Patiromer'.)
Zirconium cyclosilicate for hyperkalemia (November 2014)
Sodium zirconium cyclosilicate (ZS-9) is an orally administered inorganic, nonabsorbable crystalline compound that exchanges both sodium and hydrogen ions for potassium throughout its intestinal transit. The efficacy of ZS-9 in chronically hyperkalemic outpatients was evaluated in two nearly identical phase III randomized placebo-controlled trials [28,29]. ZS-9 doses of 5 to 10 g thrice daily reduced the mean serum potassium by 0.3 to 0.6 meq/L as compared with placebo. Edema was more common with higher doses of ZS-9, although serious adverse events were similar. The steepest decline in serum potassium occurred during the first four hours of therapy. This suggests an acute effect on intestinal potassium secretion, rather than simply a reduction in potassium absorption. Neither trial evaluated the long-term efficacy and safety of ZS-9, and neither studied patients with acute hyperkalemia or end-stage renal disease. ZS-9 is not currently approved or available for clinical use. (See "Treatment and prevention of hyperkalemia in adults", section on 'Zirconium cyclosilicate'.)
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