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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: Jan 2016. | This topic last updated: Feb 01, 2016.

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

suPAR and decreased eGFR after cardiac catheterization (November 2015)

The soluble urokinase-type plasminogen activator receptor (suPAR) is a membrane protein that has been implicated in the pathogenesis of glomerular diseases including focal and segmental glomerulosclerosis (FSGS) and diabetic nephropathy. Plasma suPAR concentrations were measured in individuals enrolled in a prospective registry of patients undergoing cardiac catheterization [1]. Patients were excluded who had congenital heart disease, severe valvular heart disease, severe anemia, a recent blood transfusion, myocarditis or an active inflammatory condition, or cancer. A higher suPAR concentration at baseline was associated with a greater annual decline in eGFR among patients with baseline eGFR <60 mL/min/1.73 m2. A role for suPAR as a biomarker of chronic kidney disease requires further study in other cohorts [2]. (See "Screening for chronic kidney disease", section on 'Other biomarkers'.)

Effect of finerenone in diabetic nephropathy (October 2015)

Mineralocorticoid receptor antagonists (MRAs) reduce proteinuria in patients with diabetic nephropathy, whether used alone or in combination with an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Finerenone, an investigational nonsteroidal MRA that may be associated with less hyperkalemia than other MRAs, was evaluated in a phase 2 dose-finding trial of 823 patients with type 2 diabetes treated with an ACE inhibitor or ARB [3]. A dose-dependent effect was observed at 90 days, with albuminuria reductions ranging from 21 to 38 percent at doses ranging from 7.5 mg/day to 20 mg/day. The incidence of hyperkalemia with finerenone treatment was low (1.5 percent); acute reductions in glomerular filtration rate were mild and were reversible after cessation of the study drug. The long-term effects of MRAs, including finerenone, in patients with diabetic nephropathy is unknown, and they should not be routinely used in these patients until such data are available. (See "Treatment of diabetic nephropathy", section on 'Mineralocorticoid receptor antagonism'.)

Terlipressin versus midodrine and octreotide for hepatorenal syndrome (July 2015)

Terlipressin, a vasopressin analog, is used for the treatment of hepatorenal syndrome, but is not approved for use in the United States. In a trial that randomly assigned 49 patients with hepatorenal syndrome to terlipressin plus albumin or to midodrine and octreotide plus albumin, the rate of complete response (a decrease in serum creatinine to less than 1.5 mg/dL [133 micromol/L] at 14 days) was significantly greater with terlipressin plus albumin (56 versus 5 percent) [4]. However, the partial response rate was greater with midodrine and octreotide plus albumin, and mortality rates did not differ; in addition, the dose of midodrine used was lower than often employed in clinical practice, and blood pressures were lower in the group who received midodrine and octreotide plus albumin. Thus, despite this and other limited trials showing benefit from terlipressin, it remains unclear whether this therapy is superior to the combination of midodrine and octreotide. (See "Hepatorenal syndrome", section on 'Terlipressin plus albumin where available'.)

DIALYSIS

Venous thromboembolism risk with central versus peripheral insertion of central venous catheters (January 2016)

There is accumulating evidence that peripherally-inserted central venous catheters (PICCs) are associated with a greater risk for upper extremity deep vein thrombosis (UEDVT) compared with centrally-inserted central venous catheters (CICCs). The Medical Inpatients and Thrombosis (MITH) Study evaluated catheter use in 299 venous thromboembolism cases compared with controls without venous thromboembolism at a single institution [5]. Central catheter use was associated with a 14-fold increased risk for UEDVT, without a significantly increased risk for pulmonary embolism. PICCs were associated with a higher cumulative risk compared with CICCs (8.1 versus 4.8 per 1000 admissions). Given the higher risk for UEDVT with PICCs, we generally avoid them in patients for whom maintaining vascular patency and integrity for long-term vascular access options (eg, future hemodialysis access) is essential. (See "Catheter-related upper extremity venous thrombosis", section on 'Peripheral versus central insertion' and "Overview of central venous access".)

GLOMERULAR DISEASE AND VASCULITIS

Immunosuppressive therapy in IgA nephropathy (December 2015)

Glucocorticoid monotherapy may be beneficial in patients with IgA nephropathy who have persistent proteinuria >1 g/day despite nonimmunosuppressive therapy, provided that such patients do not have extensive chronic fibrosis on kidney biopsy. In the STOP-IgA trial, 162 patients with IgA nephropathy and persistent proteinuria >0.75 g/day despite six months of nonimmunosuppressive therapy were assigned to continue nonimmunosuppressive therapy alone or to receive immunosuppressive therapy (glucocorticoids alone or combined with cyclophosphamide and azathioprine, depending upon the level of kidney function) [6]. At three years, the protein-to-creatinine ratio decreased to <0.2 g/g in 11 percent of patients who received nonimmunosuppressive therapy alone, 31 percent of those who received glucocorticoid monotherapy, and 11 percent of those who received combination immunosuppression. However, the change in estimated glomerular filtration rate (GFR) was not different between the groups, and immunosuppression led to more adverse events. Various trial limitations may have impacted these results and thus, UpToDate has not altered its recommendation to use immunosuppressive therapy in selected patients with IgA nephropathy and persistent proteinuria despite nonimmunosuppressive therapy. (See "Treatment and prognosis of IgA nephropathy", section on 'Glucocorticoids as sole immunosuppressive/anti-inflammatory therapy'.)

HYPERTENSION

Olmesartan enteropathy (January 2016)

Olmesartan, an angiotensin receptor blocker (ARB), can produce a "sprue-like enteropathy" characterized by severe chronic diarrhea and weight loss, occurring months to years after initiation of the drug. The largest experience comes from a French cohort of over 4 million patients who initiated therapy with olmesartan, a different ARB, or an angiotensin converting enzyme (ACE) inhibitor [7]. Compared with users of ACE inhibitors, intestinal malabsorption severe enough to cause hospitalization occurred substantially more often among patients taking olmesartan for one to two years (adjusted risk ratio 3.7) and among those taking olmesartan for more than two years (adjusted risk ratio 10.6). Risk was not increased in users of other ARBs. Although a large number of patients (ie, 12,550) needed to be treated with olmesartan for two or more years to produce one additional case of enteropathy requiring hospitalization, less severe but still clinically significant cases of enteropathy may have been more frequent. Patients starting olmesartan should be cautioned about the possibility of developing diarrhea and weight loss. The drug should be stopped if these symptoms occur and another cause is not identified. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers", section on 'Enteropathy with olmesartan'.)

SPRINT trial on goal blood pressure (November 2015, Modified December 2015)

Goal blood pressure in most hypertensive patients had been <140/90 mmHg, or <150/90 mmHg in older adults. The potential benefit of lowering the systolic blood pressure goal in nondiabetic older adults with risk factors for cardiovascular disease or with chronic kidney disease was evaluated in the Systolic Blood Pressure Intervention Trial (SPRINT), a multicenter, randomized, open-label trial performed in 9361 hypertensive patients in the United States [8]. Patients were randomly assigned to a standard treatment group (target systolic pressure <140 mmHg) or an intensive treatment group (target systolic pressure <120 mmHg); the diastolic goal in both groups was <90 mmHg. Blood pressure during the trial was measured using automated oscillometric blood pressure (AOBP) and not using manual (ausculatory) blood pressure (perhaps more commonly used in routine practice), typically yielding readings 5 to 10 mm lower than with manual measurement. In the SPRINT trial, consecutive automated blood pressure readings were taken with the patient at rest and averaged. After a median of 3.26 years, intensive as compared with standard treatment reduced the rate of the primary end point, a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular death (5.2 versus 6.8 percent), and also reduced mortality (3.3 versus 4.5 percent). Intensive treatment increased the rates of acute kidney injury, syncope, and hyponatremia, but not orthostatic hypotension or falls resulting in hospitalization.

As a result of the SPRINT trial, UpToDate now recommends lower systolic pressure goals (depending on the method of measurement) for nondiabetic adults 50 years and older at high risk for cardiovascular events, and suggests such goals for patients with diabetes. Goals for other groups, including those with proteinuric chronic kidney disease, have not changed based upon the SPRINT data. A trial examining goal blood pressure for patients with diabetes is likely to report findings for this population in 2016. (See "What is goal blood pressure in the treatment of hypertension?", section on 'Benefit according to overall cardiovascular risk' and "Goal blood pressure in patients with cardiovascular disease or at high risk".)

New guidelines on screening and diagnosis of hypertension (October 2015)

New guidelines from the United States Preventive Services Task Force (USPSTF) and the Canadian Hypertension Education Program (CHEP) have been released and suggest that, in nearly all patients who have an elevated blood pressure measured in the office, out-of-office blood pressure readings should be obtained to confirm the diagnosis [9,10]. For out-of-office blood pressure measurement, 24-hour ambulatory blood pressure monitoring (ABPM) is preferred, and home blood pressure monitoring is an acceptable alternative if ABPM is not possible. These guidelines are consistent with our recommendations for confirming elevated blood pressure readings. (See "Overview of hypertension in adults", section on 'Diagnosis'.)

Spironolactone in resistant hypertension (October 2015)

The effect of spironolactone in patients with resistant hypertension has been evaluated in several randomized trials. The best data come from the PATHWAY-2 trial, a randomized crossover study comparing spironolactone (25 to 50 mg/day) with placebo, doxazosin, or bisoprolol in 285 patients with resistant hypertension (mean clinic blood pressure 157/90 mmHg and mean home blood pressure 148/84 mmHg despite therapy with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, a calcium channel blocker, and a diuretic) [11]. Spironolactone significantly reduced mean home systolic pressure at 12 weeks (by 10, 5, and 6 mmHg compared with placebo, doxazosin, and bisoprolol, respectively). Spironolactone (or another mineralocorticoid receptor antagonist) is the treatment of choice in patients with resistant hypertension. (See "Treatment of resistant hypertension", section on 'Mineralocorticoid receptor antagonists'.)

PEDIATRIC NEPHROLOGY

Early volume expansion in STEC-hemolytic uremic syndrome (January 2016)

Fluid management of patients with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) has been based on assessment of intravascular volume, which can be increased or decreased. However, a prospective Italian study of 38 children with STEC-HUS from 2012 and 2014 compared with historical controls from 2006 to 2009 reported that routine early volume expansion targeted to increase body weight by 10 percent improved outcome (lower rate of renal replacement therapy, shorter hospital course, and shorter duration of intensive care) [12]. Although these results are promising, further investigation is needed due to the potential bias from the use of historical controls and the relatively small number of patients and adverse events in the study. Until confirmatory data are available, we recommend assessment of intravascular volume status and renal function, with administration of fluids to rapidly correct documented volume depletion. We recommend not routinely providing volume expansion, especially if there is evidence of increased intravascular volume. (See "Treatment and prognosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) in children", section on 'Fluid management'.)

TRANSPLANTATION

Estimation of ESRD risk for kidney donor candidates (December 2015)

To improve the evaluation and selection of living kidney donors, a Kidney Disease Improving Global Outcomes (KDIGO) work group and the Chronic Kidney Disease-Prognosis Consortium (CKD-PC) developed a risk prediction model for end stage renal disease (ESRD) in the absence of donation [13]. The model was based on a meta-analysis of seven general population cohorts combined with an analysis of the incidence of ESRD in a low-risk segment of the United States (US) population. The observed incidence of ESRD at 15 years among US kidney donors was 3.5 to 5.3 times the projected risks for healthy persons in the absence of donation, and varied according to sex and race. An online risk tool was developed to project ESRD risk (in the absence of donation) for donor candidates. Further research is needed to validate these results, and to extend the models to non-US populations and other racial groups. (See "Risk of live kidney donation", section on 'End-stage renal disease'.)

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 [14]. 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'.)

OTHER NEPHROLOGY

Tenofovir alafenamide as part of a coformulated antiretroviral regimen (November 2015)

Tenofovir is a preferred nucleoside to use in a combination antiretroviral regimen for the treatment of HIV infection. Until recently, tenofovir was available only as tenofovir-disoproxil fumarate (TDF), which has been associated with renal toxicity and decreased bone mineral density. As of November 2015, a newer formulation, tenofovir alafenamide (TAF), is available in the United States as part of a single tablet co-formulation, elvitegravir-cobicistat-emtricitabine-TAF (ECF-TAF) [15]. This combination agent is as effective as elvitegravir-cobicistat-emtricitabine-TDF (ECF-TDF) in suppressing HIV RNA with fewer adverse renal and bone effects [16]. ECF-TAF can be used for patients with reduced kidney function (estimated glomerular filtration rate [eGFR] ≥30 mL/min/m2), unlike ECF-TDF, which should only be used in patients with an eGFR >70 mL/min/m2. ECF-TAF is considered a recommended regimen by the United States Department of Health and Human Services [17]. TAF is not yet available as a single agent or in other combinations. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient", section on 'Preferred regimens'.)

Thrombotic microangiopathy caused by a defect in cobalamin metabolism (September 2015)

A number of thrombotic microangiopathies (TMAs) must be considered in a patient with microangiopathic hemolytic anemia (MAHA) and thrombocytopenia, including thrombotic thrombocytopenic purpura (TTP) and Shiga toxin-mediated hemolytic uremic syndrome (ST-HUS). A recent case report describes a previously healthy 18-year-old who presented with MAHA, thrombocytopenia, and renal failure with negative testing for TTP and ST-HUS [18]. He was found to have cobalamin C deficiency, with elevated plasma homocysteine and methylmalonic acid (MMA) levels and a mutation in MMACHC, a gene involved in cobalamin (vitamin B12) metabolism. Treatment with vitamin B12, betaine, and folinic acid resulted in a dramatic recovery. His brother had died of a similar syndrome at the same age. Patients with unexplained MAHA and thrombocytopenia should be evaluated for this disorder, which has an unknown prevalence and for which a safe and inexpensive therapy is readily available [19]. (See "Approach to the patient with suspected TTP, HUS, or other thrombotic microangiopathy (TMA)", section on 'Overview of primary TMA syndromes'.)

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REFERENCES

  1. Hayek SS, Sever S, Ko YA, et al. Soluble Urokinase Receptor and Chronic Kidney Disease. N Engl J Med 2015; 373:1916.
  2. Skorecki KL, Freedman BI. A suPAR Biomarker for Chronic Kidney Disease. N Engl J Med 2015; 373:1971.
  3. Bakris GL, Agarwal R, Chan JC, et al. Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial. JAMA 2015; 314:884.
  4. Cavallin M, Kamath PS, Merli M, et al. Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: A randomized trial. Hepatology 2015; 62:567.
  5. Winters JP, Callas PW, Cushman M, et al. Central venous catheters and upper extremity deep vein thrombosis in medical inpatients: the Medical Inpatients and Thrombosis (MITH) Study. J Thromb Haemost 2015; 13:2155.
  6. Rauen T, Eitner F, Fitzner C, et al. Intensive Supportive Care plus Immunosuppression in IgA Nephropathy. N Engl J Med 2015; 373:2225.
  7. Basson M, Mezzarobba M, Weill A, et al. Severe intestinal malabsorption associated with olmesartan: a French nationwide observational cohort study. Gut 2015.
  8. SPRINT Research Group, Wright JT Jr, Williamson JD, et al. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2015; 373:2103.
  9. Siu AL, U.S. Preventive Services Task Force. Screening for High Blood Pressure in Adults: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 2015; 163:778.
  10. Daskalopoulou SS, Rabi DM, Zarnke KB, et al. The 2015 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol 2015; 31:549.
  11. Williams B, MacDonald TM, Morant S, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet 2015; 386:2059.
  12. Ardissino G, Tel F, Possenti I, et al. Early Volume Expansion and Outcomes of Hemolytic Uremic Syndrome. Pediatrics 2016; 137:1.
  13. Grams ME, Sang Y, Levey AS, et al. Kidney-Failure Risk Projection for the Living Kidney-Donor Candidate. N Engl J Med 2015.
  14. 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.
  15. United States Food and Drug Administration. FDA approves new treatment for HIV. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm471300.htm (Accessed on November 16, 2015).
  16. Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet 2015; 385:2606.
  17. HHS Panel on antiretroviral guidelines for adults and adolescents includes a fixed-dose combination of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide among the recommended regimens for antiretroviral treatment-naive individuals with HIV-1 infection. https://aidsinfo.nih.gov/news/1621/evg-c-ftc-taf-statement-from-adult-arv-guideline-panel (Accessed on November 20, 2015).
  18. Grangé S, Bekri S, Artaud-Macari E, et al. Adult-onset renal thrombotic microangiopathy and pulmonary arterial hypertension in cobalamin C deficiency. Lancet 2015; 386:1011.
  19. George JN. Cobalamin C deficiency-associated thrombotic microangiopathy: uncommon or unrecognised? Lancet 2015; 386:1012.
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