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What's new in nephrology and hypertension

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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2014. | This topic last updated: Nov 25, 2014.

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.


Renal prognosis in patients with type 1 diabetes and nephropathy (October 2014)

Historically, the majority of patients with type 1 diabetes who develop severely increased albuminuria (urine albumin excretion >300 mg per day, formerly "macroalbuminuria" or "overt nephropathy") progressed to end-stage renal disease (ESRD). However, with modern management, severely increased albuminuria may regress, and rates of ESRD may be less than 20 percent at 10 years. In the DCCT/EDIC type 1 diabetes cohort, 123 patients developed severely increased albuminuria that was persistent at two consecutive study visits [1]. During the subsequent 10 years, 58 percent of these patients regressed to <300 mg of albuminuria per day, and 12 percent regressed to <30 mg per day. The 10-year rates of reduced estimated glomerular filtration rate (eGFR, <60 mL/min/1.73 m2) and ESRD in these patients with severely increased albuminuria were 34 and 18 percent, respectively. Lower HbA1c and blood pressure values were associated with a greater frequency of albuminuria regression and a lower incidence of reduced eGFR and ESRD. Thus, even patients who develop overt nephropathy can avoid progressive renal impairment. (See "Overview of diabetic nephropathy", section on 'Type 1 diabetes'.)

Fenoldopam does not improve outcomes in cardiac surgery patients with early acute kidney injury (October 2014)

Fenoldopam, a dopamine receptor-1 agonist, has been studied for the prevention and treatment of acute kidney injury (AKI) following cardiac surgery with inconsistent results from small studies. A large multicenter randomized trial compared fenoldopam to placebo in 667 patients admitted to an intensive care unit with acute kidney injury (AKI) following cardiac surgery [2]. Compared with placebo, there was no decrease in the need for renal replacement therapy or in 30-day mortality in patients who received fenoldopam. However, hypotension occurred more frequently in the fenoldopam group compared with placebo. We agree with the 2012 KDIGO guidelines that fenoldopam not be used to treat acute kidney injury. (See "Possible prevention and therapy of postischemic (ischemic) acute tubular necrosis", section on 'Fenoldopam'.)

Smoking and asbestos exposure increase risk of retroperitoneal fibrosis (September 2014)

Exposure to asbestos and tobacco smoke may result in a multiplicative increase in the risk of retroperitoneal fibrosis. This was suggested by a case control study that matched patients with idiopathic retroperitoneal fibrosis with control patients of similar age, sex, and geographic region [3]. Both smoking alone and asbestos alone increased the risk of retroperitoneal fibrosis. However, the combination of smoking and asbestos was associated with a much greater increase in risk (about eight- to 12-fold) than that conferred by either smoking (about threefold) or asbestos exposure (about fourfold) alone. (See "Clinical manifestations and diagnosis of retroperitoneal fibrosis", section on 'Etiology and risk factors'.)

Elevated troponin levels and mortality in chronic kidney disease (September 2014)

A large meta-analysis examined the diagnostic and prognostic capability of cardiac troponins T (cTnT) and I (cTnI) among chronic kidney disease (CKD) patients [4-6]. Both cTnT and cTnI were shown to have low specificity for the diagnosis of acute myocardial infarction (AMI) [5]. However, among CKD patients who did not have AMI, elevated cTnT was associated with a threefold increase in all-cause mortality and cTnI was associated with a 2.7-fold increase in all-cause mortality [4]. (See "Serum cardiac biomarkers in patients with renal failure", section on 'Troponins' and "Serum cardiac biomarkers in patients with renal failure", section on 'Use of troponins in prognosis'.)

Left ventricular end-diastolic pressure-guided fluid administration may decrease risk of contrast nephropathy (June 2014)

A randomized trial tested the benefit of a fluid replacement protocol guided by left ventricular end-diastolic pressure (LVEDP) among patients with chronic kidney disease (CKD) and other risk factors for contrast-induced acute kidney injury (AKI) [7]. The trial included 350 patients, all of whom received intravenous isotonic saline 3 mL/kg for one hour prior to cardiac catheterization, after which the rate of fluid administration was adjusted based upon LVEDP in the intervention group, while the control group received 1.5 mL/kg/hour. Contrast-induced AKI (defined as >0.5 mg/dL or >25 percent increase in serum creatinine between one and four days after the procedure) occurred less frequently in the LVEDP. These findings suggest that, among patients who are undergoing cardiac catheterization, an aggressive fluid strategy based upon LVEDP may provide benefit, although this approach should be confirmed in other centers with larger numbers of patients before it can be recommended. (See "Prevention of contrast-induced nephropathy", section on 'Left ventricular end-diastolic pressure'.)


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 [8]. 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 remission. 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 (MMF), 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 MMF, and prednisone was compared with high-dose cyclophosphamide and prednisone in 368 Chinese patients with LN [9]. At 24 weeks, the rate of complete remission, 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 remission; 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 remission. 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'.)

Anti-PLA2R autoantibody testing for primary membranous nephropathy (July 2014)

Autoantibodies against the phospholipase A2 receptor (anti-PLA2R) are present in the great majority of patients with primary (idiopathic) membranous nephropathy (MN); serologic tests for anti-PLA2R are highly sensitive and specific for a diagnosis of primary MN [10-14]. The US Food and Drug Administration (FDA) has approved two commercially available tests for anti-PLA2R, including an indirect immunofluorescence assay and an enzyme-linked immunosorbent assay

Testing for anti-PLA2R is particularly useful in nephrotic patients who cannot undergo kidney biopsy, since a positive test essentially rules out other causes of nephrotic syndrome (such as minimal change disease or focal segmental glomerulosclerosis). In addition, a positive test in someone diagnosed with MN by kidney biopsy may help distinguish primary from secondary MN. (See "Causes and diagnosis of membranous nephropathy", section on 'Laboratory testing'.)

Prophylactic anticoagulation in membranous nephropathy (May 2014)

The decision to administer prophylactic anticoagulation to patients with nephrotic syndrome due to membranous nephropathy depends upon balancing the risks of thromboembolism and anticoagulation-associated bleeding. An online tool was created that estimates thromboembolism and bleeding risk using data from two large glomerular disease cohorts [15]. In patients with membranous nephropathy and nephrotic syndrome who do not have a contraindication to anticoagulation, the potential benefits of prophylactic anticoagulation are likely to outweigh the potential harms in those with a low bleeding risk and a serum albumin <3.0 mg/dL (30 g/L); and in those with an intermediate bleeding risk and a serum albumin <2.0 mg/dL (20 g/L). In contrast, the potential harms are likely to outweigh the benefits in patients who have a high bleeding risk, regardless of the serum albumin. (See "Renal vein thrombosis and hypercoagulable state in nephrotic syndrome", section on 'Approach to prophylactic anticoagulation'.)


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 [16]. 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'.)

Long-term effect of antihypertensive therapy in diabetic patients (October 2014)

The ADVANCE trial randomly assigned 11,000 diabetic patients to a fixed combination of perindopril-indapamide or placebo for approximately four years. The trial included both patients with and without hypertension, and concomitant therapy with other blood pressure medication during the trial was at the discretion of the patient's physician. 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 [17]. 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 after completion of the trial 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 significantly lower among those in the treatment group (hazard ratio 0.91, 95% CI 0.84-0.99). 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'.)


Initial imaging in patients with suspected nephrolithiasis (September 2014)

Computerized tomography (CT) and ultrasonography as initial imaging strategies were compared in a large multicenter randomized trial [18]. Patients presenting to an emergency department (ED) with suspected nephrolithiasis (but without signs of another serious diagnosis) were assigned to initial imaging with a non-contrast helical CT scan, ultrasonography performed by a radiologist, or ultrasonography performed at the bedside by an ED physician. Subsequent evaluation and care was at the discretion of the treating clinicians. The sensitivity for stone detection was lower for ultrasonography than CT scan (54 percent if performed by an ED physician or 57 percent performed by a radiologist compared with 88 percent for CT). A CT scan was performed in 41 percent of patients who initially underwent ultrasonography while 5 percent of patients who initially had a CT subsequently had ultrasonography. Despite the lower sensitivity of ultrasonography, the rates of important missed diagnoses that resulted in complications, such as pyelonephritis with sepsis or diverticular abscess, were similar (0.5 percent with ultrasonography versus 0.3 percent with CT). Serious adverse events and return visits to the ED after discharge were also similar. Patients assigned to receive an initial CT were exposed to more than twice as much radiation during the initial ED visit than those assigned ultrasonography although, because many patients assigned ultrasonography ultimately underwent CT, the differences in cumulative radiation exposure at six months were less dramatic. While we previously suggested a non-contrast helical CT scan as the test of choice for most patients with suspected nephrolithiasis, we now consider that both CT and ultrasonography are acceptable initial imaging modalities in patients with suspected nephrolithiasis who have a low clinical suspicion for an alternative serious diagnosis. In such patients, ultrasonography leads to less radiation exposure than CT and equivalent overall outcomes. (See "Diagnosis and acute management of suspected nephrolithiasis in adults", section on 'Tests of choice: Non-contrast CT scan or ultrasonography'.)

Alpha blocker therapy to facilitate kidney stone passage (May 2014)

Several medical interventions have been used to increase the passage rate of ureteral stones, including antispasmodic agents, calcium channel blockers, and alpha blockers. In a meta-analysis of 32 trials that enrolled 5864 patients, ureteral stone passage occurred more frequently with alpha blocker therapy versus conservative treatment alone (77 versus 52 percent); in addition, stone passage occurred an average of three days faster with alpha blocker therapy [19]. In four trials that compared tamsulosin (an alpha blocker) with nifedipine (a calcium channel blocker), the stone passage rate was significantly higher with tamsulosin. We suggest treatment with tamsulosin (0.4 mg once daily) for four weeks to facilitate spontaneous stone passage in patients with stones ≤10 mm in diameter. (See "Diagnosis and acute management of suspected nephrolithiasis in adults", section on 'Facilitating stone passage'.)


Rituximab for relapsing or steroid-dependent nephrotic syndrome (July 2014)

A randomized trial has confirmed previous observational findings that rituximab, a chimeric anti-CD20 monoclonal antibody that depletes B-cell lymphocytes, is effective in prolonging remission in children with severe nephrotic syndrome [20]. In this study of 48 children with frequently relapsing or steroid-dependent nephrotic syndrome, compared with placebo, four weekly doses of rituximab (375 mg/m2) increased median duration of remission and decreased average daily prednisolone dose. Although rituximab decreased relapse at one year, all patients in both groups relapsed by 19 months. Rituximab has been associated with serious complications, including some that resulted in death. Outside of clinical trials, use of rituximab for nephrotic syndrome should be restricted to children with frequent relapses and significant medication-related adverse effects. (See "Treatment of idiopathic nephrotic syndrome in children", section on 'Rituximab'.)

Prophylactic antibiotics for children with vesicoureteral reflux (May 2014)

The results of the Randomized Intervention for Vesicoureteral Reflux (RIVUR) trial help to clarify treatment options for children with vesicoureteral reflux (VUR). Earlier studies evaluating the effectiveness of prophylactic antibiotics in preventing recurrent urinary tract infection (UTI) or renal scarring have had inconsistent findings and/or were methodologically limited. The RIVUR trial compared daily treatment with trimethoprim-sulfamethoxazole (TMP-SMX) or placebo in 607 children (two months to six years) with grade I to IV VUR diagnosed after a febrile or symptomatic UTI [21]. At the two-year follow-up, the risk of renal scarring was similar, but TMP-SMX reduced the risk of recurrent febrile or symptomatic UTI by 50 percent. These findings support our approach to VUR management. For children with grade III or higher VUR, who are more likely to have recurrent UTI (even with prophylaxis) and renal scarring, we provide prophylactic antibiotics or surgical treatment. For children with grade I or II VUR, who are more likely to have spontaneous resolution, we discuss the risks and benefits of antibiotic prophylaxis versus observation with the family. (See "Management of vesicoureteral reflux", section on 'Antibiotic prophylaxis versus surveillance/placebo trials'.)


Alemtuzumab induction regimen for immunosuppression in renal transplantation (October 2014)

The optimal immunosuppression induction therapy for renal transplant recipients is not known. In a randomized trial that compared a steroid-free regimen of alemtuzumab induction followed by low-dose tacrolimus and mycophenolate with basiliximab induction followed by standard-dose tacrolimus, mycophenolate and steroids, patients who received alemtuzumab had a lower rate of biopsy-proven rejection [22]. There was no difference between groups in transplant failure or infection. These findings require confirmation by additional studies before steroid-free regimens should be considered a routine option for maintenance therapy in transplant recipients. (See "Induction immunosuppressive therapy in renal transplantation in adults", section on 'Alemtuzumab'.)

MTORC inhibitors and antiphospholipid syndrome in kidney transplant recipients (September 2014)

Inhibitors of the mammalian target of rapamycin complex (MTORC) may decrease the recurrence of antiphospholipid syndrome (APS)-associated vascular lesions among kidney transplant recipients [23]. The activation of MTORC signalling pathways was demonstrated in cultured vascular endothelial cells treated with IgG antibodies from patients with APS. Allograft biopsies from transplant recipients with antiphospholipid antibodies who were receiving sirolimus, an MTORC inhibitor, showed decreased hyperplasia of endothelial cells, compared with biopsies from patients with antiphospholipid antibodies who did not receive sirolimus. Additionally, allograft function appeared to be better preserved among APS patients who received sirolimus. (See "Antiphospholipid syndrome and the kidney", section on 'Renal transplantation'.)


Discontinuation of eculizumab therapy for complement-mediated hemolytic uremic syndrome (September 2014)

Eculizumab, a humanized recombinant monoclonal antibody targeting complement protein C5, is an effective therapy for the majority of patients with complement-mediated hemolytic uremic syndrome (HUS), a life-threatening condition. However, it is unknown if discontinuation of eculizumab therapy, an expensive intervention with significant adverse effects, results in a high relapse rate and if lifelong therapy is thus needed. Limited data from a small observational study suggest that discontinuation may be feasible, as 7 of 10 patients remained in remission after eculizumab therapy was stopped [24]. In three patients, relapse occurred within six weeks of stopping therapy, but all three patients completely recovered when therapy was resumed. Additional studies are needed to confirm if eculizumab therapy can be discontinued and, if so, to define the optimal setting. (See "Complement-mediated hemolytic uremic syndrome", section on 'Adverse effects'.)

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