Economic evaluation of dialysis therapies.
Klarenbach Scott W,Tonelli Marcello,Chui Betty,Manns Braden J
Nature reviews. Nephrology
The prevalence of chronic kidney disease and end-stage renal disease requiring dialysis therapy continues to increase worldwide, and despite technological advances, treatment remains resource intensive. Thus, the increasing burden of dialysis therapy on finite health-care budgets is an important consideration. The principles of allocative efficiency and the concept of 'opportunity cost' can be used to assess whether dialysis is economically justified; if dialysis is to be provided, cost-minimization and cost-utility analyses can be used to identify the most efficient dialysis modality. Existing studies have examined the cost, and where relevant the effectiveness, of the various currently available peritoneal dialysis and haemodialysis modalities. In this Review, we discuss variations in the intrinsic costs of the available dialysis modalities as well as other factors, such as variation by country, available health-care infrastructures, the timing of dialysis initiation and renal transplantation. We draw on data from robust micro-costing studies of the various dialysis modalities in Canada to highlight key issues.
10.1038/nrneph.2014.145
A clinical review of peritoneal dialysis.
Bersenas Alexa M E
Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001)
OBJECTIVE:To review the principles and practice of peritoneal dialysis in veterinary medicine. DATA SOURCES:Clinical and experimental studies and current guideline recommendations from the human literature; and original case studies, case reports, and previous reviews in the veterinary literature. SUMMARY:Peritoneal dialysis involves the exchange of solutes and fluid between the peritoneal capillary blood and the dialysis solution across the peritoneal membrane. It requires placement of a peritoneal dialysis catheter for repeated dialysate exchange. The ideal catheter provides reliable, rapid dialysate flow rates without leaks or infections. Catheter selection and placement are reviewed along with dialysate selection, exchange prescriptions, and overall patient management. PD does not require specific or complex equipment, and it can achieve effective control of uremia and electrolyte imbalances. CONCLUSIONS:Peritoneal dialysis is a potential life-saving measure for patients with acute renal failure. Peritoneal dialysis results in gradual decline in uremic toxins. Previously low success rates have been reported. Improved success rates have been noted in dogs with acute kidney injury (AKI) secondary to leptospirosis. Cats also have a good success rate when PD is elected in patients with a potentially reversible underlying disease. Overall, PD remains a viable intervention for patients with AKI unresponsive to medical management. In select patients a favorable outcome is attained whereby PD provides temporary support until return of effective renal function is attained.
10.1111/j.1476-4431.2011.00679.x
Peritoneal dialysis--experiences.
Mirković Tatjana Durdević
Medicinski pregled
Peritoneal dialysis is the method of treatment of terminal-stage chronic kidney failure. Nowadays, this method is complementary to haemodialysis. It is based on the principles of the diffusion of solutes and ultrafiltration of fluids across the peritoneal membrane, which acts as a filter. The dialysate is introduced into the peritoneum via the previously positioned peritoneal catheter. The peritoneal dialysis is carried out on daily basis, at home by the patient, and the "exchange" is repeated 4-5 times during the 24 hours. The first steps in peritoneal dialysis at the Department for Haemodialysis of the Clinical Centre of Vojvodina date back to 1973. Until 1992, the patients were subjected to this program only sporadically. Since 1998 the peritoneal dialysis method has been performed at the Clinic for Nephrology and Clinical Immunology. In the period 1998-2008 ninety nine peritoneal catheters were placed. Chronic glomerulonephritis, nephroangiosclerosis and diabetes were identified as the most common causes of chronic renal failure. Two methods of catheter placement were applied: the standard open surgery method (majority of patients) and laparoscopy. Most of the patients were subjected to continuous ambulatory peritoneal dialysis, whereas four patients received automatic dialysis. Transplantation was performed in 10 patients, i.e. cadaveric transplantation and living-related donor transplantation, each in 5 patients. Peritoneal dialysis was available as a service outside our institution as well. A ten-year experience in peritoneal dialysis gained at our Centre has proved the advantages and qualities of this method, strongly supporting its wider application in the treatment of terminal-stage chronic kidney failure.
The truth on current peritoneal dialysis: state of the art.
Krediet R T,Abrahams A C,de Fijter C W H,Betjes M G H,Boer W H,van Jaarsveld B C,Konings C J A M,Dekker F W
The Netherlands journal of medicine
The share of peritoneal dialysis (PD) in the spectrum of chronic dialysis has decreased markedly in the Netherlands in the last 15 years. Consequently, the knowledge of nephrologists and nursing staff on PD has declined leading to a negative spiral in which loss of experience resulted in loss of enthusiasm to offer PD to patients and also in less interest in the new PD developments. All these changes took place while the results of PD improved and patient survival was at least similar to that on haemodialysis. The aim of this review is first to give a summary of the principles and practice of patient and staff education and to describe the role of the medical contribution in decision-making. On this basis, the second aim is to update internist-nephrologists on a number of issues that have been underexposed in the past. Recent patient and technique survival data of PD patients is reviewed, and also the new insights into dialysis adequacy. The presence of residual renal function is the main determinant of patient survival together with prevention of overhydration. Urea and creatinine removal are not important at all when patients are still passing urine. Many early problems with PD are due to the peritoneal catheter and suggestions are made for improvement of its function. The prevention and management of infections is reviewed, and also the regular assessment of peritoneal function. Free water transport is a predictor of encapsulating peritoneal sclerosis (EPS), which should be assessed regularly. The pathogenesis of EPS, treatment and the decreasing incidence are discussed.
Pharmacokinetics of culture-directed antibiotics for the treatment of peritonitis in automated peritoneal dialysis: A systematic narrative review.
Ling Chau Wei,Sud Kamal,Van Connie,Zaidi Syed Tabish Razi,Patel Rahul P,Peterson Gregory M,Castelino Ronald L
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis
The objectives of this study were to provide a summary of the pharmacokinetic data of some intraperitoneal (IP) antibiotics that could be used for both empirical and culture-directed therapy, as per the ISPD recommendations, and examine factors to consider when using IP antibiotics for the management of automated peritoneal dialysis (APD)-associated peritonitis. A literature search of PubMed, EMBASE, Scopus, MEDLINE and Google Scholar for articles published between 1998 and 2020 was conducted. To be eligible, articles had to describe the use of antibiotics via the IP route in adult patients ≥18 years old on APD in the context of pharmacokinetic studies or case reports/series. Articles describing the use of IP antibiotics that had been recently reviewed (cefazolin, vancomycin, gentamicin and ceftazidime) or administered for non-APD-associated peritonitis were excluded. A total of 1119 articles were identified, of which 983 abstracts were screened. Seventy-three full-text articles were assessed for eligibility. Eight records were included in the final study. Three reports had pharmacokinetic data in patients on APD without peritonitis. Each of cefepime 15 mg/kg IP, meropenem 0.5 g IP and fosfomycin 4 g IP given in single doses achieved drug plasma concentrations above the minimum inhibitory concentration for treating the susceptible organisms. The remaining five records were case series or reports in patients on APD with peritonitis. While pharmacokinetic data support intermittent cefepime 15 mg/kg IP daily, only meropenem 0.5 g IP and fosfomycin 4 g IP are likely to be effective if given in APD exchanges with dwell times of 15 h. Higher doses may be required in APD with shorter dwell times. Information on therapeutic efficacy was derived from case reports/series in individual patients and without therapeutic drug monitoring. Until more pharmacokinetic data are available on these antibiotics, it would be prudent to shift patients who develop peritonitis on APD to continuous ambulatory peritoneal dialysis, where pharmacokinetic information is more readily available.
10.1177/0896860821990528
Peritoneal Dialysis Access Associated Infections.
Bieber Scott,Mehrotra Rajnish
Advances in chronic kidney disease
Infection is a significant driver of morbidity and mortality in patients with end-stage renal disease undergoing maintenance dialysis. In the United States, septicemia and other infections account for 8% deaths in patients undergoing dialysis. In patients undergoing peritoneal dialysis (PD), PD-related peritonitis remains the most frequent treatment-related infection and is the greatest contributor to infection-related morbidity, including risk for hospitalization, and temporary or permanent transfer to hemodialysis. In the 4 decades since the introduction of ambulatory PD in clinical practice, a large number of treatment innovations have been shown to be effective in reducing the risk for exit site infection and PD-related peritonitis. Notwithstanding the evidence for efficacy of these innovations and the numerous adverse health consequences with PD-related peritonitis, the uptake of these interventions in clinical practice around the world remains inconsistent. This article reviews current knowledge with regards to prevention of PD-associated infections, and the diagnosis and management of exit site infections and peritonitis.
10.1053/j.ackd.2018.09.002
The pharmacokinetics of antibiotics used to treat peritoneal dialysis-associated peritonitis.
Johnson C A,Zimmerman S W,Rogge M
American journal of kidney diseases : the official journal of the National Kidney Foundation
Antibiotics continue to be used frequently to treat CAPD-associated peritonitis. Selection of appropriate antibiotic doses and routes of administration has been based largely upon clinical experience. Early pharmacokinetic studies utilized patients being treated with IPD. The relevance of these studies to CAPD remains unknown. Little information exists on the effects of peritonitis on peritoneal drug transport. Until the effects of peritonitis during CAPD are better understood, pharmacokinetic data will be of limited value in designing specific treatment recommendations for this common complication of peritoneal dialysis.
Peritoneal Dialysis.
Andreoli Maria Claudia Cruz,Totoli Claudia
Revista da Associacao Medica Brasileira (1992)
Peritoneal dialysis (PD) is a renal replacement therapy based on infusing a sterile solution into the peritoneal cavity through a catheter and provides for the removal of solutes and water using the peritoneal membrane as the exchange surface. This solution, which is in close contact with the capillaries in the peritoneum, allows diffusion solute transport and osmotic ultrafiltration water loss since it is hyperosmolar to plasma due to the addition of osmotic agents (most commonly glucose). Infusion and drainage of the solution into the peritoneal cavity can be performed in two ways: manually (continuous ambulatory PD), in which the patient usually goes through four solution changes throughout the day, or machine-assisted PD (automated PD), in which dialysis is performed with the aid of a cycling machine that allows changes to be made overnight while the patient is sleeping. Prescription and follow-up of PD involve characterizing the type of peritoneal transport and assessing the offered dialysis dose (solute clearance) as well as diagnosing and treating possible method-related complications (infectious and non-infectious).
10.1590/1806-9282.66.S1.37
Delayed versus early initiation of renal replacement therapy for severe acute kidney injury: a systematic review and individual patient data meta-analysis of randomised clinical trials.
Gaudry Stéphane,Hajage David,Benichou Nicolas,Chaïbi Khalil,Barbar Saber,Zarbock Alexander,Lumlertgul Nuttha,Wald Ron,Bagshaw Sean M,Srisawat Nattachai,Combes Alain,Geri Guillaume,Jamale Tukaram,Dechartres Agnès,Quenot Jean-Pierre,Dreyfuss Didier
Lancet (London, England)
BACKGROUND:The timing of renal replacement therapy (RRT) for severe acute kidney injury is highly debated when no life-threatening complications are present. We assessed whether a strategy of delayed versus early RRT initiation affects 28-day survival in critically ill adults with severe acute kidney injury. METHODS:In this systematic review and individual patient data meta-analysis, we searched MEDLINE (via PubMed), Embase, and the Cochrane Central Register of Controlled Trials for randomised trials published from April 1, 2008, to Dec 20, 2019, that compared delayed and early RRT initiation strategies in patients with severe acute kidney injury. Trials were eligible for inclusion if they included critically ill patients aged 18 years or older with acute kidney injury (defined as a Kidney Disease: Improving Global Outcomes [KDIGO] acute kidney injury stage 2 or 3, or, where KDIGO was unavailable, a renal Sequential Organ Failure Assessment score of 3 or higher). We contacted the principal investigator of each eligible trial to request individual patient data. From the included trials, any patients without acute kidney injury or who were not randomly allocated were not included in the individual patient data meta-analysis. The primary outcome was all-cause mortality at day 28 after randomisation. This study is registered with PROSPERO (CRD42019125025). FINDINGS:Among the 1031 studies identified, one study that met the eligibility criteria was excluded because the recruitment period was not recent enough, and ten (including 2143 patients) were included in the analysis. Individual patient data were available for nine studies (2083 patients), from which 1879 patients had severe acute kidney injury and were randomly allocated: 946 (50%) to the delayed RRT group and 933 (50%) to the early RRT group. 390 (42%) of 929 patients allocated to the delayed RRT group and who had available data did not receive RRT. The proportion of patients who died by day 28 did not significantly differ between the delayed RRT group (366 [44%] of 837) and the early RRT group (355 [43%] of 827; risk ratio 1·01 [95% CI 0·91 to 1·13], p=0·80), corresponding to an overall risk difference of 0·01 (95% CI -0·04 to 0·06). There was no heterogeneity across studies (I=0%; τ=0), and most studies had a low risk of bias. INTERPRETATION:The timing of RRT initiation does not affect survival in critically ill patients with severe acute kidney injury in the absence of urgent indications for RRT. Delaying RRT initiation, with close patient monitoring, might lead to a reduced use of RRT, thereby saving health resources. FUNDING:None.
10.1016/S0140-6736(20)30531-6
Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis.
Barbar Saber D,Clere-Jehl Raphaël,Bourredjem Abderrahmane,Hernu Romain,Montini Florent,Bruyère Rémi,Lebert Christine,Bohé Julien,Badie Julio,Eraldi Jean-Pierre,Rigaud Jean-Philippe,Levy Bruno,Siami Shidasp,Louis Guillaume,Bouadma Lila,Constantin Jean-Michel,Mercier Emmanuelle,Klouche Kada,du Cheyron Damien,Piton Gaël,Annane Djillali,Jaber Samir,van der Linden Thierry,Blasco Gilles,Mira Jean-Paul,Schwebel Carole,Chimot Loïc,Guiot Philippe,Nay Mai-Anh,Meziani Ferhat,Helms Julie,Roger Claire,Louart Benjamin,Trusson Remi,Dargent Auguste,Binquet Christine,Quenot Jean-Pierre,
The New England journal of medicine
BACKGROUND:Acute kidney injury is the most frequent complication in patients with septic shock and is an independent risk factor for death. Although renal-replacement therapy is the standard of care for severe acute kidney injury, the ideal time for initiation remains controversial. METHODS:In a multicenter, randomized, controlled trial, we assigned patients with early-stage septic shock who had severe acute kidney injury at the failure stage of the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification system but without life-threatening complications related to acute kidney injury to receive renal-replacement therapy either within 12 hours after documentation of failure-stage acute kidney injury (early strategy) or after a delay of 48 hours if renal recovery had not occurred (delayed strategy). The failure stage of the RIFLE classification system is characterized by a serum creatinine level 3 times the baseline level (or ≥4 mg per deciliter with a rapid increase of ≥0.5 mg per deciliter), urine output less than 0.3 ml per kilogram of body weight per hour for 24 hours or longer, or anuria for at least 12 hours. The primary outcome was death at 90 days. RESULTS:The trial was stopped early for futility after the second planned interim analysis. A total of 488 patients underwent randomization; there were no significant between-group differences in the characteristics at baseline. Among the 477 patients for whom follow-up data at 90 days were available, 58% of the patients in the early-strategy group (138 of 239 patients) and 54% in the delayed-strategy group (128 of 238 patients) had died (P=0.38). In the delayed-strategy group, 38% (93 patients) did not receive renal-replacement therapy. Criteria for emergency renal-replacement therapy were met in 17% of the patients in the delayed-strategy group (41 patients). CONCLUSIONS:Among patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy. (Funded by the French Ministry of Health; IDEAL-ICU ClinicalTrials.gov number, NCT01682590 .).
10.1056/NEJMoa1803213
Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit.
Gaudry Stéphane,Hajage David,Schortgen Fréderique,Martin-Lefevre Laurent,Pons Bertrand,Boulet Eric,Boyer Alexandre,Chevrel Guillaume,Lerolle Nicolas,Carpentier Dorothée,de Prost Nicolas,Lautrette Alexandre,Bretagnol Anne,Mayaux Julien,Nseir Saad,Megarbane Bruno,Thirion Marina,Forel Jean-Marie,Maizel Julien,Yonis Hodane,Markowicz Philippe,Thiery Guillaume,Tubach Florence,Ricard Jean-Damien,Dreyfuss Didier,
The New England journal of medicine
BACKGROUND:The timing of renal-replacement therapy in critically ill patients who have acute kidney injury but no potentially life-threatening complication directly related to renal failure is a subject of debate. METHODS:In this multicenter randomized trial, we assigned patients with severe acute kidney injury (Kidney Disease: Improving Global Outcomes [KDIGO] classification, stage 3 [stages range from 1 to 3, with higher stages indicating more severe kidney injury]) who required mechanical ventilation, catecholamine infusion, or both and did not have a potentially life-threatening complication directly related to renal failure to either an early or a delayed strategy of renal-replacement therapy. With the early strategy, renal-replacement therapy was started immediately after randomization. With the delayed strategy, renal-replacement therapy was initiated if at least one of the following criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg per deciliter, or oliguria for more than 72 hours after randomization. The primary outcome was overall survival at day 60. RESULTS:A total of 620 patients underwent randomization. The Kaplan-Meier estimates of mortality at day 60 did not differ significantly between the early and delayed strategies; 150 deaths occurred among 311 patients in the early-strategy group (48.5%; 95% confidence interval [CI], 42.6 to 53.8), and 153 deaths occurred among 308 patients in the delayed-strategy group (49.7%, 95% CI, 43.8 to 55.0; P=0.79). A total of 151 patients (49%) in the delayed-strategy group did not receive renal-replacement therapy. The rate of catheter-related bloodstream infections was higher in the early-strategy group than in the delayed-strategy group (10% vs. 5%, P=0.03). Diuresis, a marker of improved kidney function, occurred earlier in the delayed-strategy group (P<0.001). CONCLUSIONS:In a trial involving critically ill patients with severe acute kidney injury, we found no significant difference with regard to mortality between an early and a delayed strategy for the initiation of renal-replacement therapy. A delayed strategy averted the need for renal-replacement therapy in an appreciable number of patients. (Funded by the French Ministry of Health; ClinicalTrials.gov number, NCT01932190.).
10.1056/NEJMoa1603017
Effect of Hemodiafiltration or Hemodialysis on Mortality in Kidney Failure.
The New England journal of medicine
BACKGROUND:Several studies have suggested that patients with kidney failure may benefit from high-dose hemodiafiltration as compared with standard hemodialysis. However, given the limitations of the various published studies, additional data are needed. METHODS:We conducted a pragmatic, multinational, randomized, controlled trial involving patients with kidney failure who had received high-flux hemodialysis for at least 3 months. All the patients were deemed to be candidates for a convection volume of at least 23 liters per session (as required for high-dose hemodiafiltration) and were able to complete patient-reported outcome assessments. The patients were assigned to receive high-dose hemodiafiltration or continuation of conventional high-flux hemodialysis. The primary outcome was death from any cause. Key secondary outcomes were cause-specific death, a composite of fatal or nonfatal cardiovascular events, kidney transplantation, and recurrent all-cause or infection-related hospitalizations. RESULTS:A total of 1360 patients underwent randomization: 683 to receive high-dose hemodiafiltration and 677 to receive high-flux hemodialysis. The median follow-up was 30 months (interquartile range, 27 to 38). The mean convection volume during the trial in the hemodiafiltration group was 25.3 liters per session. Death from any cause occurred in 118 patients (17.3%) in the hemodiafiltration group and in 148 patients (21.9%) in the hemodialysis group (hazard ratio, 0.77; 95% confidence interval, 0.65 to 0.93). CONCLUSIONS:In patients with kidney failure resulting in kidney-replacement therapy, the use of high-dose hemodiafiltration resulted in a lower risk of death from any cause than conventional high-flux hemodialysis. (Funded by the European Commission Research and Innovation; CONVINCE Dutch Trial Register number, NTR7138.).
10.1056/NEJMoa2304820
Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury.
The New England journal of medicine
BACKGROUND:Acute kidney injury is common in critically ill patients, many of whom receive renal-replacement therapy. However, the most effective timing for the initiation of such therapy remains uncertain. METHODS:We conducted a multinational, randomized, controlled trial involving critically ill patients with severe acute kidney injury. Patients were randomly assigned to receive an accelerated strategy of renal-replacement therapy (in which therapy was initiated within 12 hours after the patient had met eligibility criteria) or a standard strategy (in which renal-replacement therapy was discouraged unless conventional indications developed or acute kidney injury persisted for >72 hours). The primary outcome was death from any cause at 90 days. RESULTS:Of the 3019 patients who had undergone randomization, 2927 (97.0%) were included in the modified intention-to-treat analysis (1465 in the accelerated-strategy group and 1462 in the standard-strategy group). Of these patients, renal-replacement therapy was performed in 1418 (96.8%) in the accelerated-strategy group and in 903 (61.8%) in the standard-strategy group. At 90 days, death had occurred in 643 patients (43.9%) in the accelerated-strategy group and in 639 (43.7%) in the standard-strategy group (relative risk, 1.00; 95% confidence interval [CI], 0.93 to 1.09; P = 0.92). Among survivors at 90 days, continued dependence on renal-replacement therapy was confirmed in 85 of 814 patients (10.4%) in the accelerated-strategy group and in 49 of 815 patients (6.0%) in the standard-strategy group (relative risk, 1.74; 95% CI, 1.24 to 2.43). Adverse events occurred in 346 of 1503 patients (23.0%) in the accelerated-strategy group and in 245 of 1489 patients (16.5%) in the standard-strategy group (P<0.001). CONCLUSIONS:Among critically ill patients with acute kidney injury, an accelerated renal-replacement strategy was not associated with a lower risk of death at 90 days than a standard strategy. (Funded by the Canadian Institutes of Health Research and others; STARRT-AKI ClinicalTrials.gov number, NCT02568722.).
10.1056/NEJMoa2000741
Chronic kidney disease.
Romagnani Paola,Remuzzi Giuseppe,Glassock Richard,Levin Adeera,Jager Kitty J,Tonelli Marcello,Massy Ziad,Wanner Christoph,Anders Hans-Joachim
Nature reviews. Disease primers
Chronic kidney disease (CKD) is defined by persistent urine abnormalities, structural abnormalities or impaired excretory renal function suggestive of a loss of functional nephrons. The majority of patients with CKD are at risk of accelerated cardiovascular disease and death. For those who progress to end-stage renal disease, the limited accessibility to renal replacement therapy is a problem in many parts of the world. Risk factors for the development and progression of CKD include low nephron number at birth, nephron loss due to increasing age and acute or chronic kidney injuries caused by toxic exposures or diseases (for example, obesity and type 2 diabetes mellitus). The management of patients with CKD is focused on early detection or prevention, treatment of the underlying cause (if possible) to curb progression and attention to secondary processes that contribute to ongoing nephron loss. Blood pressure control, inhibition of the renin-angiotensin system and disease-specific interventions are the cornerstones of therapy. CKD complications such as anaemia, metabolic acidosis and secondary hyperparathyroidism affect cardiovascular health and quality of life, and require diagnosis and treatment.
10.1038/nrdp.2017.88
Association of Adolescent Hypertension With Future End-stage Renal Disease.
Leiba Adi,Fishman Boris,Twig Gilad,Gilad David,Derazne Estela,Shamiss Ari,Shohat Tamar,Ron Ofir,Grossman Ehud
JAMA internal medicine
Importance:Hypertension is a leading risk factor of cardiovascular morbidity and mortality. The role of nonmalignant hypertension as the sole initiating factor of end-stage renal disease (ESRD) in non-African American populations has recently been questioned. Objective:To investigate the association between hypertension and future ESRD in otherwise healthy adolescents. Design, Setting, and Participants:This retrospective cohort study examined the data of 16- to 19-year-old healthy candidates for military service in the Israel Defense Forces between January 1, 1967, and December 31, 2013. Data were obtained from the central conscription registry of the Israel Defense Forces and the ESRD registry of the Israel Ministry of Health. Participants underwent a comprehensive medical assessment prior to their military service. Individuals with evidence of renal damage or kidney-related risk factors were excluded. The data analysis was conducted from February 12, 2017, to October 16, 2018. Main Outcomes and Measures:End-stage renal disease as recorded by the Israeli ESRD registry, including hemodialysis, peritoneal dialysis, renal transplant diagnosed between January 1, 1990, and December 31, 2014. Results:The cohort included 2 658 238 adolescents (1 596 709 [60.1%] male with a mean [SD] age of 17.4 [0.5] years), of whom 7997 (0.3%) had an established hypertension diagnosis. Half of the individuals in the hypertensive group were overweight (1559 [20.1%]) or obese (2243 [28.9%]), and most (7235 [90.5%]) were male. During a median follow-up of 19.6 years (52 287 945 person-years), 2189 individuals developed ESRD, with an incidence rate of 3.9 per 100 000 person-years. Adolescent hypertension was found to be associated with future ESRD (crude hazard ratio [HR], 5.07; 95% CI, 3.73-6.88). In a multivariable model adjusted for sex, age, years of education, body mass index, and other sociodemographic variables, the HR was 1.98 (95% CI, 1.42-2.77). When excluding participants with severe hypertension, the association with ESRD remained statistically significant (HR, 1.93; 95% CI, 1.37-2.70). In the subanalysis of nonoverweight adolescents, the association between hypertension and ESRD was statistically significant as well (HR, 2.11; 95% CI, 1.05-4.24). Conclusions and Relevance:Hypertension appears to be associated with a doubling of the risk of future ESRD in an otherwise healthy adolescent population.
10.1001/jamainternmed.2018.7632
Assessment of Global Kidney Health Care Status.
Bello Aminu K,Levin Adeera,Tonelli Marcello,Okpechi Ikechi G,Feehally John,Harris David,Jindal Kailash,Salako Babatunde L,Rateb Ahmed,Osman Mohamed A,Qarni Bilal,Saad Syed,Lunney Meaghan,Wiebe Natasha,Ye Feng,Johnson David W
JAMA
Importance:Kidney disease is a substantial worldwide clinical and public health problem, but information about available care is limited. Objective:To collect information on the current state of readiness, capacity, and competence for the delivery of kidney care across countries and regions of the world. Design, Setting, and Participants:Questionnaire survey administered from May to September 2016 by the International Society of Nephrology (ISN) to 130 ISN-affiliated countries with sampling of key stakeholders (national nephrology society leadership, policy makers, and patient organization representatives) identified by the country and regional nephrology leadership through the ISN. Main Outcomes and Measures:Core areas of country capacity and response for kidney care. Results:Responses were received from 125 of 130 countries (96%), including 289 of 337 individuals (85.8%, with a median of 2 respondents [interquartile range, 1-3]), representing an estimated 93% (6.8 billion) of the world's population of 7.3 billion. There was wide variation in country readiness, capacity, and response in terms of service delivery, financing, workforce, information systems, and leadership and governance. Overall, 119 (95%), 95 (76%), and 94 (75%) countries had facilities for hemodialysis, peritoneal dialysis, and kidney transplantation, respectively. In contrast, 33 (94%), 16 (45%), and 12 (34%) countries in Africa had facilities for hemodialysis, peritoneal dialysis, and kidney transplantation, respectively. For chronic kidney disease (CKD) monitoring in primary care, serum creatinine with estimated glomerular filtration rate and proteinuria measurements were reported as always available in only 21 (18%) and 9 (8%) countries, respectively. Hemodialysis, peritoneal dialysis, and transplantation services were funded publicly and free at the point of care delivery in 50 (42%), 48 (51%), and 46 (49%) countries, respectively. The number of nephrologists was variable and was low (<10 per million population) in Africa, the Middle East, South Asia, and Oceania and South East Asia (OSEA) regions. Health information system (renal registry) availability was limited, particularly for acute kidney injury (8 countries [7%]) and nondialysis CKD (9 countries [8%]). International acute kidney injury and CKD guidelines were reportedly accessible in 52 (45%) and 62 (52%) countries, respectively. There was relatively low capacity for clinical studies in developing nations. Conclusions and Relevance:This survey demonstrated significant interregional and intraregional variability in the current capacity for kidney care across the world, including important gaps in services and workforce. Assuming the responses accurately reflect the status of kidney care in the respondent countries, the findings may be useful to inform efforts to improve the quality of kidney care worldwide.
10.1001/jama.2017.4046
Efficacy and Safety of Daprodustat for Treatment of Anemia of Chronic Kidney Disease in Incident Dialysis Patients: A Randomized Clinical Trial.
JAMA internal medicine
Importance:Daprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, is being evaluated as an oral alternative to conventional erythropoiesis-stimulating agent (ESA) therapy. Few studies of anemia treatment in an incident dialysis (ID) population have been reported. Objective:To evaluate the efficacy and safety of daprodustat vs darbepoetin alfa in treating anemia of chronic kidney disease in ID patients. Design, Setting, and Participants:This prospective, randomized, open-label clinical trial was conducted from May 11, 2017, through September 24, 2020, in 90 centers across 14 countries. Patients with advanced CKD were eligible if they planned to start dialysis within 6 weeks from screening or had started and received hemodialysis (HD) or peritoneal dialysis (PD) within 90 days before randomization, had a screening hemoglobin (Hb) concentration of 8.0 to 10.5 g/dL (to convert to grams per liter, multiply by 10) and a randomization Hb of 8.0 to 11.0 g/dL, were ESA-naive or had received limited ESA treatment, and were iron-replete. Interventions:Randomized 1:1 to daprodustat or darbepoetin alfa. Main Outcomes and Measures:The primary analysis in the intent-to-treat population evaluated the mean change in Hb concentration from baseline to evaluation period (weeks 28-52) to assess noninferiority of daprodustat vs darbepoetin alfa (noninferiority margin, -0.75 g/dL). The mean monthly intravenous (IV) iron dose from baseline to week 52 was the principal secondary end point. Rates of treatment-emergent and serious adverse events (AEs) were also compared between treatment groups to assess safety and tolerability. Results:A total of 312 patients (median [IQR] age, 55 [45-65] years; 194 [62%] male) were randomized to either daprodustat (157 patients; median [IQR] age, 52.0 [45-63] years; 96 [61%] male) or darbepoetin alfa (155 patients; median [IQR] age, 56.0 [45-67] years; 98 [63%] male); 306 patients (98%) completed the trial. The mean (SD) Hb concentration during the evaluation period was 10.5 (1.0) g/dL for the daprodustat and 10.6 (0.9) g/dL for the darbepoetin alfa group, with an adjusted mean treatment difference of -0.10 g/dL (95% CI, -0.34 to 0.14 g/dL), indicating noninferiority. There was a reduction in mean monthly IV iron use from baseline to week 52 in both treatment groups; however, daprodustat was not superior compared with darbepoetin alfa in reducing monthly IV iron use (adjusted mean treatment difference, 19.4 mg [95% CI, -11.0 to 49.9 mg]). Adverse event rates were 76% for daprodustat vs 72% for darbepoetin alfa. Conclusions and Relevance:This randomized clinical trial found that daprodustat was noninferior to darbepoetin alfa in treating anemia of CKD and may represent a potential oral alternative to a conventional ESA in the ID population. Trial Registration:ClinicalTrials.gov Identifier: NCT03029208.
10.1001/jamainternmed.2022.0605
Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis.
The New England journal of medicine
BACKGROUND:Among patients with chronic kidney disease (CKD), the use of recombinant human erythropoietin and its derivatives for the treatment of anemia has been linked to a possibly increased risk of stroke, myocardial infarction, and other adverse events. Several trials have suggested that hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors (PHIs) are as effective as erythropoiesis-stimulating agents (ESAs) in increasing hemoglobin levels. METHODS:In this randomized, open-label, phase 3 trial, we assigned patients with CKD who were undergoing dialysis and who had a hemoglobin level of 8.0 to 11.5 g per deciliter to receive an oral HIF-PHI (daprodustat) or an injectable ESA (epoetin alfa if they were receiving hemodialysis or darbepoetin alfa if they were receiving peritoneal dialysis). The two primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 (noninferiority margin, -0.75 g per deciliter) and the first occurrence of a major adverse cardiovascular event (a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), with a noninferiority margin of 1.25. RESULTS:A total of 2964 patients underwent randomization. The mean (±SD) baseline hemoglobin level was 10.4±1.0 g per deciliter overall. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.28±0.02 g per deciliter in the daprodustat group and 0.10±0.02 g per deciliter in the ESA group (difference, 0.18 g per deciliter; 95% confidence interval [CI], 0.12 to 0.24), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 2.5 years, a major adverse cardiovascular event occurred in 374 of 1487 patients (25.2%) in the daprodustat group and in 394 of 1477 (26.7%) in the ESA group (hazard ratio, 0.93; 95% CI, 0.81 to 1.07), which also met the prespecified noninferiority margin for daprodustat. The percentages of patients with other adverse events were similar in the two groups. CONCLUSIONS:Among patients with CKD undergoing dialysis, daprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-D ClinicalTrials.gov number, NCT02879305.).
10.1056/NEJMoa2113379