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What's new in nephrology and hypertension

What's new in nephrology and hypertension
Authors:
John P Forman, MD, MSc
Albert Q Lam, MD
Literature review current through: Mar 2022. | This topic last updated: Apr 27, 2022.

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

Predictive model for acute kidney injury following cardiac surgery (March 2022)

A model has been proposed to predict the development of acute kidney injury (AKI) following cardiac surgery. The derivation model used basic metabolic panel laboratory values from over 58,000 adult patients who underwent cardiac surgery [1]. The model had excellent predictive discrimination for moderate to severe AKI within 72 hours after surgery (area under the curve [AUC] 0.876) and similarly performed well in the validation cohort (AUC 0.860). Further data are needed to determine whether such a model improves clinical outcomes before it can be routinely used in the clinical setting. (See "Postoperative complications among patients undergoing cardiac surgery", section on 'Renal dysfunction'.)

Finerenone in patients with type 2 diabetes and less severe diabetic kidney disease (January 2022)

Patients with type 2 diabetes and diabetic kidney disease (DKD) should generally be treated with an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) plus a sodium-glucose cotransporter 2 (SGLT2) inhibitor. Finerenone, a nonsteroidal selective mineralocorticoid receptor antagonist (MRA), was shown to slow the progression of kidney function loss in a large trial of patients with type 2 diabetes and severe DKD. In a similar trial that tested the effects of this drug in over 7000 patients with less severe DKD, finerenone, compared with placebo, reduced the risk of heart failure hospitalization and nonsignificantly lowered the rate of kidney failure and all-cause mortality; the benefit from finerenone was similar in those treated and not treated with an SGLT2 inhibitor [2]. As a result of these two trials, some experts add finerenone, where available, to SGLT2 therapy provided the patient has a normal serum potassium while taking an ACE inhibitor or ARB. (See "Treatment of diabetic kidney disease", section on 'Type 2 diabetes: Treat with additional kidney-protective therapy'.)

Daprodustat for anemia treatment in nondialysis chronic kidney disease (November 2021)

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF PHIs) are a novel class of oral erythropoiesis-stimulating agents (ESAs) that are being evaluated for treatment of anemia in patients with chronic kidney disease (CKD). In a trial of nearly 4000 patients with nondialysis CKD and anemia that compared the safety and efficacy of the HIF PHI daprodustat with darbepoetin, hemoglobin concentrations increased more with daprodustat at approximately two years [3]. However, major cardiovascular events (a composite of death, nonfatal stroke, and nonfatal myocardial infarction) were also more frequent with daprodustat, a difference that was statistically significant during the active treatment period but not by the end of post-treatment follow-up. Although these data indicate that anemia can be effectively treated with daprodustat, they raise some safety concerns about this drug. (See "Treatment of anemia in nondialysis chronic kidney disease", section on 'Investigational agents'.)

DIALYSIS

Patency of early cannulation versus standard arteriovenous grafts (April 2022)

Early cannulation arteriovenous (AV) grafts reduce the time to first cannulation, which is important to reduce use of hemodialysis catheters and associated complications. Comparison of early cannulation grafts with standard grafts has only been evaluated in observational studies. Now, a trial that randomly assigned nearly 500 patients to standard or early cannulation AV grafts reported similar patency rates at 6 and 12 months without significant differences in complication rates [4]. For patients in whom an AV graft is the best hemodialysis access and the need for chronic hemodialysis is imminent, these results support the use of an early cannulation AV grafts. (See "Arteriovenous graft creation for hemodialysis and its complications", section on 'Early cannulation grafts'.)

Daprodustat for anemia in patients on dialysis (January 2022)

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF PHIs) are a novel class of oral erythropoiesis-stimulating agents (ESAs) that are being evaluated for treatment of anemia in patients with chronic kidney disease (CKD). In a trial that compared the efficacy and safety of the HIF PHI daprodustat and an injectable ESA (epoetin or darbepoetin) in over 2900 patients on dialysis, the mean change in hemoglobin concentration was 0.28 g/dL with daprodustat and 0.10 g/dL with ESA therapy over a median of 2.5 years [3]. Rates of major adverse cardiovascular events were similar between the treatment groups, as were rates of other adverse events. While these data suggest that daprodustat can effectively treat anemia in patients on dialysis, this drug is not yet approved for use outside of Japan. (See "Treatment of anemia in dialysis patients", section on 'Investigational agents'.)

FLUID, ELECTROLYTES, AND ACID-BASE BALANCE

Fluid resuscitation with saline or buffered crystalloid in adults (March 2022, Modified March 2022)

The choice between normal saline (NS) and a buffered salt solution (BSS) for initial fluid resuscitation in adults is debated. Recent large trials have failed to show superiority of one over the other [5-7]. In a new meta-analysis of six randomized trials with low risk of bias in nearly 35,000 adults requiring fluid resuscitation, BSS led to small and statistically nonsignificant reductions in both 90-day mortality (risk ratio [RR] 0.96, 95% CI 0.91-1.01) and acute kidney injury (RR 0.96, 95% CI 0.89-1.02) compared with NS [8]. Many of the trials had limitations including poor recruitment, low volumes of administered fluid, and unavailable data. In addition, the two types of fluids have differing advantages and disadvantages depending on blood chemistries and volume status. We suggest that the choice between fluids be individualized and re-evaluated following initial resuscitation. (See "Treatment of severe hypovolemia or hypovolemic shock in adults", section on 'Choosing between 0.9 percent saline and buffered crystalloid'.)

GLOMERULAR DISEASE AND VASCULITIS

FAT1-associated membranous nephropathy in hematopoietic cell transplant recipients (April 2022)

Membranous nephropathy (MN) is the most common form of the nephrotic syndrome in hematopoietic cell transplant (HCT) recipients. A new study has found that between 83 and 100 percent of patients with HCT-associated MN have antibodies directed against a novel glomerular target antigen, protocadherin FAT1 (FAT1) [9]. Although additional studies are needed to determine the cause of the alloimmune response to FAT1 in HCT recipients, these findings suggest that FAT1-associated MN may be a unique subset of MN in these patients. (See "Kidney disease following hematopoietic cell transplantation", section on 'Pathology and pathogenesis'.)

Macrophage infiltration and response to immunosuppression in IgA nephropathy (December 2021)

In patients with IgA nephropathy (IgAN), immunosuppressive therapy is generally reserved for those who are at high risk for disease progression; however, tools to identify which patients are likely to benefit from treatment are lacking. In a study of over 600 Chinese patients with IgAN at high risk for disease progression who received immunosuppressive therapy for a median of 18 months, higher levels of macrophage infiltration within glomeruli on kidney biopsy were associated with a markedly increased probability of response to immunosuppression when compared with lower levels [10]. Combining the intensity of macrophage infiltration with clinical and histologic data accurately predicted the response to immunosuppression. While these findings may help identify patients who will benefit from immunosuppressive therapy, additional validation in other patient populations is needed. (See "IgA nephropathy: Treatment and prognosis", section on 'Immunosuppressive therapy in high-risk patients'.)

Anti-nephrin antibodies in minimal change disease (November 2021)

Minimal change disease (MCD) is a common cause of the nephrotic syndrome in children and adults, but the underlying pathogenesis remains unclear. In a recent study of over 60 adults and children with biopsy-proven MCD and no known genetic basis, circulating autoantibodies targeting nephrin, an essential component of the glomerular slit diaphragm, were identified in approximately one-third of patients with active disease [11]. Punctate immunoglobulin G (IgG) deposits colocalized with nephrin in the kidney biopsies of patients who were serologically positive for anti-nephrin antibodies, whereas no deposits were present in those who were serologically negative. These findings suggest a possible autoimmune etiology for MCD in a subset of patients. (See "Minimal change disease: Etiology, clinical features, and diagnosis in adults", section on 'Role of B cells'.)

HYPERTENSION

Effect of regular acetaminophen use on blood pressure (March 2022)

Nonsteroidal anti-inflammatory drugs have well-established effects on blood pressure; however, there are fewer data about the effects of acetaminophen. In a crossover trial of approximately 100 patients with treated hypertension, regular acetaminophen (at maximum dose, 1 g four times daily) given for two weeks increased both systolic and diastolic blood pressure as compared with placebo (by 5/2 mmHg) [12]. These results, in addition to those of a prior trial, suggest that acetaminophen may have adverse effects on blood pressure in patients with hypertension. (See "NSAIDs and acetaminophen: Effects on blood pressure and hypertension", section on 'Effects of acetaminophen on blood pressure'.)

Antihypertensive effect of chlorthalidone in advanced chronic kidney disease (November 2021)

It is a commonly held belief that thiazide diuretics are not effective in patients with advanced chronic kidney disease (CKD); however, several studies indicate that thiazide diuretics are effective in such patients. In a randomized trial of 160 patients with advanced CKD (estimated GFR 15 to 29 mL/min/1.73 m2) and uncontrolled hypertension despite antihypertensive therapy, chlorthalidone substantially reduced 24-hour ambulatory blood pressure (by 10.5/3.9 mmHg) compared with placebo [13]. Hypokalemia, hyponatremia, and dizziness were more common with chlorthalidone. These data confirm findings from other studies and indicate that thiazide diuretics can be effective in controlling blood pressure among patients with advanced CKD. (See "Thiazides versus loop diuretics in the treatment of hypertension", section on 'Patients with chronic kidney disease'.)

TRANSPLANTATION

Additional COVID-19 vaccine primary series dose for immunocompromised individuals (August 2021, Modified February 2022)

COVID-19 vaccines are less effective among patients with certain immunocompromising conditions than in the general population; additional vaccine doses have been associated with improved effectiveness in this population. We agree with recommendations from the Advisory Committee on Immunization Practices (ACIP) in the United States that individuals with such conditions (table 1) receive an additional mRNA vaccine dose as part of their primary COVID-19 vaccine series (eg, following two doses of an mRNA vaccine or one dose of Ad26.COV2.S vaccine) (figure 1) [14,15]. This additional primary series dose is distinct from the booster dose, which such patients should additionally receive, although at a shorter interval than recommended for the general population. (See "COVID-19: Vaccines", section on 'Immunocompromised individuals'.)

Mode of delivery and pregnancy outcomes in kidney transplant recipients (January 2022)

Most pregnant kidney transplant recipients will undergo a cesarean delivery, but there is no clear evidence to support its routine use. In a registry study of over 1400 female kidney transplant recipients with live births, approximately two-thirds underwent a trial of labor (most with a vaginal delivery) and one-third had a scheduled cesarean birth [16]. Compared with scheduled cesarean birth, a trial of labor was not associated with an increase in severe maternal morbidity and was associated with lower odds of neonatal morbidity. Among kidney transplant recipients, vaginal birth is the preferred mode of delivery, and cesarean birth should be reserved for patients with obstetric indications only. (See "Kidney transplantation in adults: Sexual and reproductive health after kidney transplantation", section on 'Mode of delivery'.)

Fourth dose of COVID mRNA vaccine in solid organ transplant recipients (January 2022)

In solid organ transplant recipients, a third dose of a COVID-19 mRNA vaccine appears to improve the immune response; however, many have a weak response even after three prior doses. Data from three independent case series suggest that a fourth dose of an mRNA vaccine may increase antibody levels in some of these patients [17-19]. In the largest of these studies, approximately half of the 92 kidney transplant recipients who received a fourth dose mounted an appropriate serologic response (antispike IgG titer >143 binding antibody units); however, similarly robust responses were not seen across all studies. Among patients who did not respond to previous doses, the likelihood of response to additional doses was low. Administration of more than three doses of mRNA vaccine is not routinely performed; for patients who are unable to respond to multiple vaccine doses, other strategies may be required to achieve immunity. (See "COVID-19: Issues related to solid organ transplantation", section on 'Vaccination'.)

Neutralization of SARS-CoV-2 variants in transplant recipients after three doses of mRNA vaccine (December 2021)

In transplant recipients, administration of a third COVID-19 mRNA vaccine dose has been shown to improve the immune response without causing short-term adverse events; however, data on vaccine immunogenicity against SARS-CoV-2 variants are limited. In a secondary analysis of a recent randomized trial, sera obtained from participants after receipt of the third vaccine dose had greater ability to neutralize wild-type SARS-CoV-2 and Alpha, Beta, and Delta variants when compared with sera obtained after the second dose and sera from participants who received placebo [20]. The third dose was well tolerated; no cases of rejection were reported, and graft function remained stable in all patients for three months after the third dose. These findings support administering a three-dose primary vaccine series among transplant recipients and other immunocompromised patients. (See "COVID-19: Issues related to solid organ transplantation", section on 'Vaccination'.)

REFERENCES

  1. Demirjian S, Bashour CA, Shaw A, et al. Predictive Accuracy of a Perioperative Laboratory Test-Based Prediction Model for Moderate to Severe Acute Kidney Injury After Cardiac Surgery. JAMA 2022; 327:956.
  2. Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes. N Engl J Med 2021; 385:2252.
  3. Singh AK, Carroll K, Perkovic V, et al. Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis. N Engl J Med 2021; 385:2325.
  4. Tawfik AM, Zidan MH, Salem A, Salem A. A randomized controlled study of early versus standard cannulation of arteriovenous grafts in hemodialysis patients. J Vasc Surg 2022; 75:1047.
  5. Zampieri FG, Machado FR, Biondi RS, et al. Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial. JAMA 2021.
  6. Zampieri FG, Machado FR, Biondi RS, et al. Effect of Slower vs Faster Intravenous Fluid Bolus Rates on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial. JAMA 2021; 326:830.
  7. Finfer S, Micallef S, Hammond N, et al. Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults. N Engl J Med 2022; 386:815.
  8. Hammond N, Zampieri F, Di Tanna G, Garside T et. Balanced Crystalloids versus Saline in Critically Ill Adults — A Systematic Review with Meta-Analysis. NEJM Evidence 2022; https://doi.org10.1056/EVIDoa2100010.
  9. Sethi S, Madden B, Casal Moura M, et al. Hematopoietic Stem Cell Transplant-Membranous Nephropathy is Associated with Protocadherin FAT1. J Am Soc Nephrol 2022.
  10. Xie D, Zhao H, Xu X, et al. Intensity of Macrophage Infiltration in Glomeruli Predicts Response to Immunosuppressive Therapy in Patients with IgA Nephropathy. J Am Soc Nephrol 2021.
  11. Watts AJB, Keller KH, Lerner G, et al. Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology. J Am Soc Nephrol 2022; 33:238.
  12. MacIntyre IM, Turtle EJ, Farrah TE, et al. Regular Acetaminophen Use and Blood Pressure in People With Hypertension: The PATH-BP Trial. Circulation 2022; 145:416.
  13. Agarwal R, Sinha AD, Cramer AE, et al. Chlorthalidone for Hypertension in Advanced Chronic Kidney Disease. N Engl J Med 2021; 385:2507.
  14. CDC - An Additional Dose of mRNA COVID-19 Vaccine Following a Primary Series in Immunocompromised People. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-08-13/02-COVID-Dooling-508.pdf (Accessed on August 14, 2021).
  15. Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Authorized in the United States. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html (Accessed on February 24, 2022).
  16. Yin O, Kallapur A, Coscia L, et al. Mode of Obstetric Delivery in Kidney and Liver Transplant Recipients and Associated Maternal, Neonatal, and Graft Morbidity During 5 Decades of Clinical Practice. JAMA Netw Open 2021; 4:e2127378.
  17. Alejo JL, Mitchell J, Chiang TP, et al. Antibody Response to a Fourth Dose of a SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series. Transplantation 2021; 105:e280.
  18. Kamar N, Abravanel F, Marion O, et al. Assessment of 4 Doses of SARS-CoV-2 Messenger RNA-Based Vaccine in Recipients of a Solid Organ Transplant. JAMA Netw Open 2021; 4:e2136030.
  19. Caillard S, Thaunat O, Benotmane I, et al. Antibody Response to a Fourth Messenger RNA COVID-19 Vaccine Dose in Kidney Transplant Recipients: A Case Series. Ann Intern Med 2022; 175:455.
  20. Kumar D, Ferreira VH, Hall VG, et al. Neutralization of SARS-CoV-2 Variants in Transplant Recipients After Two and Three Doses of mRNA-1273 Vaccine : Secondary Analysis of a Randomized Trial. Ann Intern Med 2022; 175:226.
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