What's new in nephrology and hypertension

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

Plant-based diets and clinical outcomes in nondialysis CKD (April 2024)

Few studies have examined the association between dietary patterns and outcomes in patients with chronic kidney disease (CKD). In a prospective cohort study that included over 2500 individuals with nondialysis CKD followed for a median of 12 years, study participants with the highest adherence to overall plant-based diets and to healthy plant-based diets had a 26 and 21 percent lower risk of mortality, respectively, compared with those with the lowest adherence [1]. However, an unhealthy plant-based diet (characterized by high intakes of fruit juices, refined grains, sweets, and desserts) was associated with modestly increased risks of mortality and CKD progression. These data suggest that most patients with nondialysis CKD should consume a diet rich in fruits, vegetables, nuts, legumes, and whole grains. (See "Dietary recommendations for patients with nondialysis chronic kidney disease", section on 'Overview'.)

DIALYSIS

Prior abdominal surgery and successful peritoneal dialysis (March 2024)

Many patients with end-stage kidney disease and a history of abdominal surgery are not viewed as candidates for peritoneal dialysis (PD) because postoperative peritoneal adhesions may prevent successful PD. In a retrospective cohort study of over 850 patients undergoing their first PD catheter insertion who were followed for a median of 12 months, patients with a history of abdominal surgery had a similar incidence of complications leading to abandonment of the catheter, or to interruption or termination of PD, as patients without prior abdominal surgery (22 and 18 percent, respectively) [2]. These and other data suggest that prior abdominal surgery should not be considered a contraindication to PD and support our individualized approach to PD in such patients. (See "Evaluating patients for chronic peritoneal dialysis and selection of modality", section on 'Peritoneal scarring'.)

Increasing advance care planning for patients on dialysis (February 2024)

Although patients on dialysis have high morbidity and mortality, advance care planning (ACP) is often not well integrated into the care of this population. In a cluster randomized trial conducted in 42 dialysis clinics that included nearly 430 patients on dialysis paired with a surrogate decision-maker, patient-surrogate pairs received either a 45- to 60-minute ACP discussion led by a dialysis clinic health care worker (eg, registered nurse or social worker) or usual care [3]. After two weeks, patient-surrogate pairs in the ACP group had greater congruence on end-of-life care goals and lower patient decisional conflict compared with those in the usual care group. Strategies that involve patient caregivers and dialysis unit staff can increase uptake of ACP among patients on dialysis. (See "Kidney palliative care: Principles, benefits, and core components", section on 'Advance care planning'.)

Lack of efficacy of insomnia therapies for patients on dialysis (February 2024)

Although insomnia may affect nearly half of patients on dialysis, relatively few studies have evaluated the efficacy of commonly used insomnia therapies in this population. In a trial in which over 120 patients on hemodialysis with insomnia were randomly assigned to treatment with cognitive behavior therapy for insomnia (CBT-I), trazodone, or placebo for six weeks, there were no significant differences in the change in Insomnia Severity Index scores from baseline among the three groups after 7 or 25 weeks, but serious cardiovascular events were more frequent in the trazodone group [4]. The inclusion of patients with obstructive sleep apnea and other factors may have masked a potential benefit of CBT-I. Based on these data and previous studies reporting associations between the use of hypnotic medications and adverse outcomes in patients on dialysis, we prefer nonpharmacologic therapy for the treatment of insomnia in patients with end-stage kidney disease; more studies are needed to delineate the role of CBT-I in these patients. (See "Sleep disorders in end-stage kidney disease", section on 'Treatment'.)

Severe hypocalcemia with denosumab therapy in dialysis-treated patients (February 2024)

Denosumab use is not restricted in individuals with osteoporosis who have advanced kidney disease. However, concerns remain regarding the risk of severe hypocalcemia in such patients. In a cohort study of 2804 female patients (aged ≥65 years) with osteoporosis and undergoing dialysis, severe hypocalcemia (serum calcium <7.5 mg/dL [1.9 mmol/L] or hypocalcemia requiring emergency care) occurred in a higher proportion of patients who initiated denosumab compared with those who initiated an oral bisphosphonate (12-week weighted cumulative incidence 41.1 versus 2 percent, respectively) [5]. Denosumab also was associated with a higher incidence of very severe hypocalcemia (serum calcium <6.5 mg/dL [1.6 mmol/L]). A boxed warning about risk of severe hypocalcemia in individuals with advanced kidney disease, especially patients on dialysis, has been added for brand name denosumab (Prolia) [6], underscoring the need for greater caution and increased monitoring during treatment. (See "Denosumab for osteoporosis", section on 'Hypocalcemia'.)

Taurolidine catheter locks for the prevention of hemodialysis catheter-related bloodstream infections (December 2023)

Catheter-related bloodstream infections (CRBSIs) are an important cause of morbidity and mortality in patients on hemodialysis. In a randomized trial of nearly 800 patients on maintenance hemodialysis via a tunneled central venous catheter, a catheter lock solution containing taurolidine, an antimicrobial agent, plus heparin reduced the incidence of CRBSI compared with a heparin control lock solution (2 versus 8 percent) over a mean of 200 days [7]. No trial participants used chlorhexidine-coated catheter caps, which are commonly used to reduce the risk of CRBSI. Based on these results, taurolidine lock solutions are a reasonable alternative to chlorhexidine-coated catheter caps to help prevent CRBSIs in select patients. (See "Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Management and prevention", section on 'Methods we use'.)

FLUID, ELECTROLYTES, AND ACID-BASE BALANCE

Veverimer and chronic kidney disease progression in patients with metabolic acidosis (March 2024)

In patients with chronic kidney disease (CKD) and metabolic acidosis, alkali therapy may slow the decline in kidney function. In a trial in which nearly 1500 patients with CKD and metabolic acidosis were randomly assigned to veverimer (an investigational gastrointestinal acid binder that increases serum bicarbonate) or placebo, 20 percent of patients in each group had CKD progression at two years, defined as a ≥40 percent decline in estimated glomerular filtration rate (eGFR), kidney failure, or death from kidney disease [8]. However, because of an unexpected increase in serum bicarbonate in the placebo arm, the separation in serum bicarbonate concentration between the two groups during the trial was minimal (approximately 1 mEq/L), and therefore this trial could not address whether correction of metabolic acidosis delays progression of CKD. We continue to suggest alkali therapy in patients with CKD and metabolic acidosis. (See "Pathogenesis, consequences, and treatment of metabolic acidosis in chronic kidney disease", section on 'Choice of therapy'.)

Diagnosis of arginine vasopressin deficiency (central diabetes insipidus) versus primary polydipsia (February 2024)

It can be difficult to distinguish arginine vasopressin deficiency (AVP-D) from primary polydipsia in patients who present with polyuria and polydipsia; if reliable plasma copeptin measurements are available, these two disorders can be differentiated by measuring plasma copeptin after hypertonic saline infusion (to induce hypernatremia) or after intravenous arginine infusion. In a trial that compared both approaches, the diagnostic accuracy was higher when combining copeptin measurement with hypertonic saline infusion as compared with arginine infusion (96 versus 74 percent) [9]. Despite the superior accuracy of hypertonic saline infusion, the response to arginine infusion can be used as the initial test because it is easier to perform, generally preferred by patients, and highly accurate if the postarginine copeptin level remains below 3 pmol/L (which is specific for AVP-D) or rises above 5.2 pmol/L (which is highly specific for primary polydipsia). If the postarginine copeptin level is intermediate, then hypertonic saline infusion can be performed. (See "Evaluation of patients with polyuria", section on 'If water restriction is nondiagnostic'.)

GLOMERULAR DISEASE AND VASCULITIS

Antithyroid drugs and ANCA-associated vasculitis (May 2024)

Some cases of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) have been linked to the use of antithyroid drugs (ATD), although data are limited. In a recent retrospective study of 45 patients with ATD-induced AAV, nearly half were positive for myeloperoxidase (MPO)-ANCA, and 33 percent were positive for both MPO-ANCA and proteinase 3 (PR3)-ANCA [10]. Patients were most likely to present with cutaneous manifestations and arthralgias; in 16 percent of cases, discontinuation of the ATD led to resolution of vasculitis, while the remaining patients were treated with an immunosuppressive agent. This study highlights that some patients with ATD-induced AAV may not require immunosuppression, and that ATD-induced AAV should be considered in patients who present with both MPO-ANCA and PR3-ANCA, a combination rarely seen in other forms of AAV. (See "Clinical spectrum of antineutrophil cytoplasmic autoantibodies", section on 'Drug-induced ANCA-associated vasculitis'.)

Sibeprenlimab for IgA nephropathy (December 2023)

A Proliferation-Inducing Ligand (APRIL) is critical for mucosal B cell survival, maturation, and proliferation and has been implicated in the pathogenesis of IgA nephropathy (IgAN). The efficacy and safety of sibeprenlimab, an investigational monoclonal antibody against APRIL, were evaluated in a phase II trial in which over 150 patients with IgAN and persistent proteinuria despite optimized supportive care were randomly assigned to intravenous sibeprenlimab (2, 4, or 8 mg/kg body weight) or placebo once monthly for 12 months [11]. At 12 months, patients receiving sibeprenlimab had a greater, dose-dependent reduction in proteinuria; rates of serious adverse events were similar among the treatment groups. A larger phase III trial is in progress. (See "IgA nephropathy: Treatment and prognosis", section on 'Investigational agents'.)

Sparsentan in patients with IgA nephropathy (December 2023)

Patients with IgA nephropathy (IgAN) generally receive a renin-angiotensin system (RAS) inhibitor to reduce proteinuria, but proteinuria may persist despite maximally tolerated therapy. The efficacy and safety of sparsentan, a dual angiotensin II receptor and endothelin-1 receptor antagonist, were evaluated in a phase 3 trial in which over 400 adults with IgAN and persistent proteinuria despite three months of optimized supportive care were randomly assigned to sparsentan or irbesartan once daily [12,13]. At week 110, patients receiving sparsentan had a greater reduction in proteinuria and a smaller decline in two-year estimated glomerular filtration rate (eGFR) chronic slope; while rates of serious adverse events were similar between the groups, hypotension, dizziness, and acute kidney injury were more frequent with sparsentan. We consider sparsentan as an alternative option to reduce proteinuria in patients with IgAN and persistent proteinuria ≥1 g/day despite optimal treatment with an RAS inhibitor and a sodium-glucose cotransporter 2 (SGLT2) inhibitor for at least three to six months. (See "IgA nephropathy: Treatment and prognosis", section on 'Dual endothelin angiotensin receptor antagonists'.)

Trial of sparsentan in focal segmental glomerulosclerosis (December 2023)

Patients with focal segmental glomerulosclerosis (FSGS) are commonly treated with renin-angiotensin system (RAS) inhibitors to reduce proteinuria and stabilize kidney function. In a phase 3 trial in which over 370 patients with an FSGS lesion on kidney biopsy or a genetic variant associated with FSGS were randomly assigned to sparsentan, a dual endothelin receptor and angiotensin II receptor antagonist, or to the angiotensin II receptor antagonist irbesartan, sparsentan-treated patients had a greater reduction in proteinuria at 36 and 108 weeks, but there was no significant difference between the groups in estimated glomerular filtration rate (eGFR) slope at 108 weeks [14]. The discrepancy between sparsentan's effects on proteinuria and eGFR may reflect the enrollment of a heterogeneous mix of patients with primary, secondary, and genetic FSGS, who have a fundamentally different pathogenesis and disease course. Based on these findings, we do not use sparsentan in patients with an FSGS lesion. (See "Focal segmental glomerulosclerosis: Treatment and prognosis", section on 'Investigational therapies'.)

HYPERTENSION

Monitoring after negative confirmatory testing for primary aldosteronism (February 2024)

After a positive screening test for primary aldosteronism, confirmatory testing is required for diagnosis. In individuals with a positive screening test but negative confirmatory testing, the optimal monitoring strategy is uncertain. In a study that prospectively followed 184 individuals with a positive screening test for primary aldosteronism but negative confirmatory testing, a screening test was repeated after at least two years of follow-up [15]. If positive, confirmatory testing was performed again. Over a mean follow-up of five years, 20 percent of participants were diagnosed with primary aldosteronism. Those who developed primary aldosteronism exhibited higher blood pressure between initial and repeat testing despite similarly aggressive antihypertensive therapy. These findings support repeat testing for primary aldosteronism in individuals with initially negative confirmatory testing, particularly in those with progressively treatment-refractory blood pressure. (See "Diagnosis of primary aldosteronism", section on 'Negative confirmatory testing'.)

NEPHROLITHIASIS

Drug therapy to prevent recurrent urinary stone disease (May 2024)

In patients with kidney stones, drug therapy to reduce stone recurrence is indicated if the stone disease remains active or there is insufficient improvement in urine chemistries despite dietary modification; however, evidence for its effectiveness is limited. In a study of over 5600 adults with urinary stone disease and at least one urinary abnormality (hypercalciuria, hypocitraturia, or hyperuricosuria), drug therapy (thiazide diuretics, alkali therapy, or uric acid-lowering medications) was associated with a 19 percent lower risk of clinically significant recurrent stone disease over 12 to 36 months compared with no treatment [16]. This benefit did not reach statistical significance over longer follow-up periods; however, important factors that could potentially affect treatment efficacy (eg, use of appropriate drug doses, treatment adherence) were not reported. For patients with recurrent calcium oxalate stones, we tailor drug therapy based upon the presence of specific metabolic abnormalities. (See "Kidney stones in adults: Prevention of recurrent kidney stones", section on 'Drug therapy for specific metabolic abnormalities'.)

Tranexamic acid to reduce bleeding after percutaneous nephrolithotomy (December 2023)

Postoperative bleeding can occur after percutaneous nephrolithotomy (PNL) for kidney stone removal; most bleeding is venous in origin and can be managed with conservative measures. A recent meta-analysis of 10 randomized trials found that use of tranexamic acid (TXA), an antifibrinolytic agent used to reduce bleeding in other clinical settings, may reduce the risk of blood transfusion after PNL [17]. Most trials were conducted in low- to middle-income settings in populations that were younger than those in higher-income settings; whether these findings are generalizable to practice in higher-income settings is uncertain. Pending additional data, we do not routinely use TXA after PNL. (See "Kidney stones in adults: Surgical management of kidney and ureteral stones", section on 'Bleeding'.)

PEDIATRIC NEPHROLOGY

Association between obesity in adolescence and development of chronic kidney disease (April 2024)

Observational studies have suggested that adolescents with obesity are at increased risk for impaired kidney function. In a new study of 630,000 adolescents in Israel, high body mass index (BMI) in late adolescence was associated with development of chronic kidney disease in early adulthood, as measured by albuminuria [18]. For severe obesity, the adjusted hazard ratio for early chronic kidney disease was 9.4 for males and 4.3 for females. These findings support our suggestion to screen for impaired kidney function in patients with risk factors for chronic kidney disease, including severe obesity, hypertension, or type 2 diabetes. Screening consists of measuring urine albumin-to-creatinine ratio. (See "Overview of the health consequences of obesity in children and adolescents", section on 'Kidney'.)

Serial amnioinfusions for bilateral renal agenesis (January 2024)

Bilateral renal agenesis (BRA) is incompatible with extrauterine life because prolonged oligohydramnios results in pulmonary hypoplasia, leading to postnatal respiratory failure. A prospective study (RAFT) assessed use of serial amnioinfusions to treat 18 cases of BRA diagnosed at <26 weeks of gestation [19]. Of the 17 live births, 14 survived ≥14 days and had placement of dialysis access, but only 6 survived to hospital discharge. Of the 4 children alive at 9 to 24 months of age, 3 had experienced a stroke and none had undergone transplant. These findings show that serial amnioinfusions for BRA mitigates pulmonary hypoplasia and increases short-term survival and access to dialysis; however, long-term outcome remains poor with no survival to transplantation. Serial amnioinfusions remain investigational and should be offered only as institutional review board-approved research. (See "Renal agenesis: Prenatal diagnosis", section on 'Investigative role of therapeutic amnioinfusion'.)

TRANSPLANTATION

HIV-positive donor kidney transplantation under the HOPE Act (May 2024)

Kidney transplantation is now accepted as standard of care for patients with HIV and end-stage kidney disease (ESKD). In 2013, the United States Congress passed the HIV Organ Policy Equity (HOPE) Act, which permitted research in the area of HIV-positive-to-HIV-positive transplantation; since then, several deceased, HIV-positive donor kidney transplants have been performed. In an analysis of over 300 transplant candidates listed for HIV-positive donor kidneys within HOPE trials (ie, HOPE candidates) and over 46,000 candidates not listed for HIV-positive donor kidneys (ie, non-HOPE candidates), HOPE candidates had higher rates of kidney transplantation (70 versus 43 percent) at 4.5 years and a shorter waitlist time (10 versus 61 months) [20]. For kidney transplant candidates with HIV, listing for HIV-positive donor kidneys under the HOPE Act improved access to transplantation, supporting expansion of this practice. (See "Kidney transplantation in patients with HIV", section on 'Donors with HIV'.)

First transplant of a genetically edited pig kidney into a living human (March 2024)

For patients with end-stage kidney disease (ESKD), kidney transplantation is generally preferred over dialysis but is limited by the severe shortage of donated human organs. On March 16, 2024, the first ever transplantation of a genetically modified pig kidney into a living patient with ESKD was performed under a US Food and Drug Administration expanded access protocol (ie, compassionate use) [21]. The recipient was treated with tegoprubart (an anti-CD40 ligand antibody) and ravulizumab (an anti-complement C5 monoclonal antibody); the xenograft was reported to be functioning well one week after surgery. While this initial report is encouraging, further details on the function and safety of this procedure await full publication of the findings. (See "Kidney transplantation in adults: Xenotransplantation", section on 'Clinical studies in humans'.)