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Dialysis for Chronic Kidney Failure

Author/s: 
Jennifer E. Flythe, Kristin L. Walter

Selection of hemodialysis or peritoneal dialysis and timing of dialysis initiation are influenced by patient symptoms, laboratory trajectories, patient preferences, and therapy cost and availability; shared decision-making is key. Jennifer E. Flythe, MD, MPH, from the University of North Carolina, discusses dialysis for chronic kidney failure with JAMA Deputy Editor Kristin L. Walter, MD, MS.

Keywords 
Kidney Failure chronic kidney failure Kidney dialysis

Dialysis for Chronic Kidney Failure: A Review

Author/s: 
Jennifer E Flythe, Suzanne Watnick

Importance: More than 3.5 million people worldwide and 540 000 individuals in the US receive maintenance hemodialysis or peritoneal dialysis for the treatment of chronic kidney failure. The 5-year survival rate is approximately 40% after initiation of maintenance dialysis.

Observations: Hemodialysis and peritoneal dialysis remove metabolic waste and excess body water and rebalance electrolytes to sustain life. There is no recommended estimated glomerular filtration rate (eGFR) threshold for initiating dialysis, and patient-clinician shared decision-making should help determine when to initiate dialysis. Persistent signs and symptoms of uremia (eg, nausea, fatigue) and volume overload (eg, dyspnea, peripheral edema), worsening eGFR, metabolic acidosis, and hyperkalemia inform the timing of therapy initiation. A randomized clinical trial reported no mortality benefit to starting dialysis at higher eGFR (10-14 mL/min/1.73 m2) vs lower eGFR (5-7 mL/min/1.73 m2) levels. Observational data suggested no differences in 5-year mortality with use of hemodialysis vs peritoneal dialysis. Cardiovascular (eg, arrhythmias, cardiac arrest) and infection-related complications of maintenance dialysis are common. In the US, hemodialysis catheter-related bloodstream infections occur at a rate of 1.1 to 5.5 episodes per 1000 catheter-days and affect approximately 50% of patients within 6 months of catheter placement. Peritonitis occurs at a rate of 0.26 episodes per patient-year and affects about 30% of individuals in the first year of peritoneal dialysis therapy. Chronic kidney failure-related systemic complications, such as anemia, hyperphosphatemia, hypocalcemia, and hypertension, often require pharmacologic treatment. Hypotension during dialysis, refractory symptoms (eg, muscle cramps, itching), and malfunction of dialysis access can interfere with delivery of dialysis.

Conclusions and relevance: In 2021, more than 540 000 patients in the US received maintenance hemodialysis or peritoneal dialysis for treatment of chronic kidney failure. Five-year survival rate after initiation of maintenance dialysis is approximately 40%, and the mortality rate is similar with hemodialysis and peritoneal dialysis. Decisions about dialysis initiation timing and modality are influenced by patient symptoms, laboratory trajectories, patient preferences, and therapy cost and availability and should include shared decision-making.

Keywords 
Kidney Failure Kidney dialysis

Systemic Lupus Erythematosus: A Review

Author/s: 
Siegel, C.H., Sammaritano, L.R.

Importance
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation and immune-mediated injury to multiple organ systems, including the mucocutaneous, musculoskeletal, hematologic, and kidney systems. Approximately 3.4 million people worldwide have received a diagnosis of SLE.

Observations
Approximately 90% of people with SLE are female. Although there are no uniformly accepted diagnostic criteria for SLE, the 2019 European Alliance of Associations for Rheumatology (formerly the European League Against Rheumatism)/American College of Rheumatology classification criteria developed for scientific study are an estimated 96.1% sensitive and 93.4% specific for SLE. These classification criteria include both clinical factors, such as fever, cytopenia, rash, arthritis, and proteinuria, which may be indicative of lupus nephritis; and immunologic measures, such as SLE-specific autoantibodies and low complement levels. Approximately 40% of people with SLE develop lupus nephritis, and an estimated 10% of people with lupus nephritis develop end-stage kidney disease after 10 years. The primary goal of treatment is to achieve disease remission or quiescence, defined by minimal symptoms, low levels of autoimmune inflammatory markers, and minimal systemic glucocorticoid requirement while the patient is treated with maintenance doses of immunomodulatory or immunosuppressive medications. Treatment goals include reducing disease exacerbations, hospitalizations, and organ damage due to the disease or treatment toxicity. Hydroxychloroquine is standard of care for SLE and has been associated with a significant reduction in mortality. Treatments in addition to hydroxychloroquine are individualized, with immunosuppressive agents, such as azathioprine, mycophenolate mofetil, and cyclophosphamide, typically used for treating moderate to severe disease. Three SLE medications were recently approved by the Food and Drug Administration: belimumab (for active SLE in 2011 and for lupus nephritis in 2020), voclosporin (for lupus nephritis), and anifrolumab (for active SLE).

Conclusions and Relevance
Systemic lupus erythematosus is associated with immune-mediated damage to multiple organs and increased mortality. Hydroxychloroquine is first-line therapy and reduces disease activity, morbidity, and mortality. When needed, additional immunosuppressive and biologic therapies include azathioprine, mycophenolate mofetil, cyclophosphamide, belimumab, voclosporin, and anifrolumab.

Keywords 
Kidney Lupus Erythematosus Lupus Nephritis Kidney Failure

Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes : A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials

Author/s: 
Pittas, A. G., Kawahara, T., Jorde, R., Dawson-Hughes, B., Vickery, E. M., Angellotti, E., Nelson, J., Trikalinos, T. A., Balk, E. M.

Background: The role of vitamin D in people who are at risk for type 2 diabetes remains unclear.

Purpose: To evaluate whether administration of vitamin D decreases risk for diabetes among people with prediabetes.

Data sources: PubMed, Embase, and ClinicalTrials.gov from database inception through 9 December 2022.

Study selection: Eligible trials that were specifically designed and conducted to test the effects of oral vitamin D versus placebo on new-onset diabetes in adults with prediabetes.

Data extraction: The primary outcome was time to event for new-onset diabetes. Secondary outcomes were regression to normal glucose regulation and adverse events. Prespecified analyses (both unadjusted and adjusted for key baseline variables) were conducted according to the intention-to-treat principle.

Data synthesis: Three randomized trials were included, which tested cholecalciferol, 20 000 IU (500 mcg) weekly; cholecalciferol, 4000 IU (100 mcg) daily; or eldecalcitol, 0.75 mcg daily, versus matching placebos. Trials were at low risk of bias. Vitamin D reduced risk for diabetes by 15% (hazard ratio, 0.85 [95% CI, 0.75 to 0.96]) in adjusted analyses, with a 3-year absolute risk reduction of 3.3% (CI, 0.6% to 6.0%). The effect of vitamin D did not differ in prespecified subgroups. Among participants assigned to the vitamin D group who maintained an intratrial mean serum 25-hydroxyvitamin D level of at least 125 nmol/L (≥50 ng/mL) compared with 50 to 74 nmol/L (20 to 29 ng/mL) during follow-up, cholecalciferol reduced risk for diabetes by 76% (hazard ratio, 0.24 [CI, 0.16 to 0.36]), with a 3-year absolute risk reduction of 18.1% (CI, 11.7% to 24.6%). Vitamin D increased the likelihood of regression to normal glucose regulation by 30% (rate ratio, 1.30 [CI, 1.16 to 1.46]). There was no evidence of difference in the rate ratios for adverse events (kidney stones: 1.17 [CI, 0.69 to 1.99]; hypercalcemia: 2.34 [CI, 0.83 to 6.66]; hypercalciuria: 1.65 [CI, 0.83 to 3.28]; death: 0.85 [CI, 0.31 to 2.36]).

Limitations: Studies of people with prediabetes do not apply to the general population. Trials may not have been powered for safety outcomes.

Conclusion: In adults with prediabetes, vitamin D was effective in decreasing risk for diabetes.

Primary funding source: None. (PROSPERO: CRD42020163522).

Keywords 
Kidney Cholecalciferol Intention to Treat Analysis type 2 diabetes Randomized Controlled Trials as Topic
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