Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome.

BACKGROUND: Primary membranous nephropathy (PMN) is a common cause of nephrotic syndrome in adults. Without treatment, approximately 30% of patients will experience spontaneous remission and one third will have persistent proteinuria. Approximately one-third of patients progress toward end-stage kidney disease (ESKD) within 10 years. Immunosuppressive treatment aims to protect kidney function and is recommended for patients who do not show improvement of proteinuria by supportive therapy, and for patients with severe nephrotic syndrome at presentation due to the high risk of developing ESKD. The efficacy and safety of different immunosuppressive regimens are unclear. This is an update of a Cochrane review, first published in 2004 and updated in 2013. OBJECTIVES: The aim was to evaluate the safety and efficacy of different immunosuppressive treatments for adult patients with PMN and nephrotic syndrome. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 1 April 2021 with support from the Cochrane Kidney and Transplant Information Specialist using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) investigating effects of immunosuppression in adults with PMN and nephrotic syndrome were included. DATA COLLECTION AND ANALYSIS: Study selection, data extraction, quality assessment, and data synthesis were performed using Cochrane-recommended methods. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Sixty-five studies (3807 patients) were included. Most studies exhibited a high risk of bias for the domains, blinding of study personnel, participants and outcome assessors, and most studies were judged unclear for randomisation sequence generation and allocation concealment. Immunosuppressive treatment versus placebo/no treatment/non-immunosuppressive treatment In moderate certainty evidence, immunosuppressive treatment probably makes little or no difference to death, probably reduces the overall risk of ESKD (16 studies, 944 participants: RR 0.59, 95% CI 0.35 to 0.99; I² = 22%), probably increases total remission (complete and partial) (6 studies, 879 participants: RR 1.44, 95% CI 1.05 to 1.97; I² = 73%) and complete remission (16 studies, 879 participants: RR 1.70, 95% CI 1.05 to 2.75; I² = 43%), and probably decreases the number with doubling of serum creatinine (SCr) (9 studies, 447 participants: RR 0.46, 95% CI 0.26 to 0.80; I² = 21%). However, immunosuppressive treatment may increase the number of patients relapsing after complete or partial remission (3 studies, 148 participants): RR 1.73, 95% CI 1.05 to 2.86; I² = 0%) and may lead to a greater number experiencing temporary or permanent discontinuation/hospitalisation due to adverse events (18 studies, 927 participants: RR 5.33, 95% CI 2.19 to 12.98; I² = 0%). Immunosuppressive treatment has uncertain effects on infection and malignancy. Oral alkylating agents with or without steroids versus placebo/no treatment/steroids Oral alkylating agents with or without steroids had uncertain effects on death but may reduce the overall risk of ESKD (9 studies, 537 participants: RR 0.42, 95% CI 0.24 to 0.74; I² = 0%; low certainty evidence). Total (9 studies, 468 participants: RR 1.37, 95% CI 1.04 to 1.82; I² = 70%) and complete remission (8 studies, 432 participants: RR 2.12, 95% CI 1.33 to 3.38; I² = 37%) may increase, but had uncertain effects on the number of patients relapsing, and decreasing the number with doubling of SCr. Alkylating agents may be associated with a higher rate of adverse events leading to discontinuation or hospitalisation (8 studies 439 participants: RR 6.82, 95% CI 2.24 to 20.71; I² = 0%). Oral alkylating agents with or without steroids had uncertain effects on infection and malignancy. Calcineurin inhibitors (CNI) with or without steroids versus placebo/no treatment/supportive therapy/steroids We are uncertain whether CNI with or without steroids increased or decreased the risk of death or ESKD, increased or decreased total or complete remission, or reduced relapse after complete or partial remission (low to very low certainty evidence). CNI also had uncertain effects on decreasing the number with a doubling of SCr, temporary or permanent discontinuation or hospitalisation due to adverse events, infection, or malignancy. Calcineurin inhibitors (CNI) with or without steroids versus alkylating agents with or without steroids We are uncertain whether CNI with or without steroids increases or decreases the risk of death or ESKD. CNI with or without steroids may make little or no difference to total remission (10 studies, 538 participants: RR 1.01, 95% CI 0.89 to 1.15; I² = 53%; moderate certainty evidence) or complete remission (10 studies, 538 participants: RR 1.15, 95% CI 0.84 to 1.56; I² = 56%; low certainty evidence). CNI with or without steroids may increase relapse after complete or partial remission. CNI with or without steroids had uncertain effects on SCr increase, adverse events, infection, and malignancy. Other immunosuppressive treatments Other interventions included azathioprine, mizoribine, adrenocorticotropic hormone, traditional Chinese medicines, and monoclonal antibodies such as rituximab. There were insufficient data to draw conclusions on these treatments. AUTHORS' CONCLUSIONS: This updated review strengthened the evidence that immunosuppressive therapy is probably superior to non-immunosuppressive therapy in inducing remission and reducing the number of patients that progress to ESKD. However, these benefits need to be balanced against the side effects of immunosuppressive drugs. The number of included studies with high-quality design was relatively small and most studies did not have adequate follow-up. Clinicians should inform their patients of the lack of high-quality evidence. An alkylating agent (cyclophosphamide or chlorambucil) combined with a corticosteroid regimen had short- and long-term benefits, but this was associated with a higher rate of adverse events. CNI (tacrolimus and cyclosporin) showed equivalency with alkylating agents however, the certainty of this evidence remains low. Novel immunosuppressive treatments with the biologic rituximab or use of adrenocorticotropic hormone require further investigation and validation in large and high-quality RCTs.

Medication discrepancies in late-stage chronic kidney disease.

BACKGROUND: Late-stage chronic kidney disease (LS-CKD) can be defined by glomerular filtration rate (GFR) 0-30 mL/min. It is a period of risk for medication discrepancies because of frequent hospitalizations, fragmented medical care, inadequate communication and polypharmacy. In this study, we sought to characterize medication discrepancies in LS-CKD. METHODS: We analyzed all patients enrolled in Northwell Health's Healthy Transitions in LS-CKD program. All patients had estimated GFR 0-30 mL/min, not on dialysis. Medications were reviewed by a nurse at a home visit. Patients' medication usage and practice were compared with nephrologists' medication lists, and discrepancies were characterized. Patients were categorized as having either no discrepancies or one or more. Associations between patient characteristics and number of medication discrepancies were evaluated by chi-square or Fisher's exact test for categorical variables, and two-sample t-test or Wilcoxon text for continuous variables. RESULTS: Seven hundred and thirteen patients with a median age of 70 (interquartile range 58-79) years were studied. There were 392 patients (55.0% of the study population) with at least one medication discrepancy. The therapeutic classes of medications with most frequently occurring medication discrepancies were cardiovascular, vitamins, bone and mineral disease agents, diuretics, analgesics and diabetes medications. In multivariable analysis, factors associated with higher risk of discrepancies were congestive heart failure [odds ratio (OR) 2.13; 95% confidence interval (CI) 1.44-3.16; P = 0.0002] and number of medications (OR 1.29; 95% CI 1.21-1.37; P < 0.0001). CONCLUSIONS: Medication discrepancies are common in LS-CKD, affect the majority of patients and include high-risk medication classes. Congestive heart failure and total number of medications are independently associated with greater risk for multiple drug discrepancies. The frequency of medication discrepancies indicates a need for great care in medication management of these patients.

Precision Medicine in the Transition to Dialysis and Personalized Renal Replacement Therapy.

Launched in 2016, the overarching goal of the Precision Medicine Initiative is to promote a personalized approach to disease management that takes into account an individual's unique underlying biology and genetics, lifestyle, and environment, in lieu of a one-size-fits-all model. The concept of precision medicine is pervasive across many areas of nephrology and has been particularly relevant to the care of advanced chronic kidney disease patients transitioning to end-stage kidney disease (ESKD). Given many uncertainties surrounding the optimal transition of incident ESKD patients to dialysis and transplantation, as well as the high mortality rates observed during this delicate transition period, there is a pressing urgency for implementing precision medicine in the management of this population. Although the traditional paradigm has been to commence incident hemodialysis patients on a 3 times/week treatment regimen, largely driven by adequacy targets, there has been growing recognition that alternative treatment regimens (ie, incremental hemodialysis) may be preferred among certain subpopulations when taking into consideration factors such as patients' residual kidney function, volume status fluctuations, symptoms, and preferences. In this review, we examine the origins of current practices in how dialysis is initiated among incident ESKD patients; incremental dialysis therapy as a dynamic and patient-centric approach that is tailored to patients' unique characteristics; recent data on the incremental hemodialysis regimen and outcomes; and future research directions using a precision nephrology approach to ESKD management with the potential to develop novel approaches, tools, and collaborative efforts to improve the health, well-being, and survival of this population.

Potentially Avoidable Readmissions in United States Hemodialysis Patients.

INTRODUCTION: Patients with end-stage kidney disease have a high risk of 30-day readmission to hospital. These readmissions are financially costly to health care systems and are associated with poor health-related quality of life. The objective of this study was to describe and analyze the frequency, causes, and predictors of 30-day potentially avoidable readmission to hospital in patients on hemodialysis. METHODS: We conducted a retrospective cohort study using the US Renal Data System data from January 1, 2008, to December 31, 2008. A total of 107,940 prevalent United States hemodialysis patients with 248,680 index hospital discharges were assessed for the main outcome of 30-day potentially avoidable readmission, as identified by a computerized algorithm. RESULTS: Of 83,209 30-day readmissions, 59,045 (70.1%) resulted in a 30-day potentially avoidable readmission. The geographic distribution of 30-day potentially avoidable readmission in the United States varied by state. Characteristics associated with 30-day potentially avoidable readmission included the following: younger age, shorter time on hemodialysis, at least 3 or more hospitalizations in preceding 12 months, black race, unemployed status, treatment at a for-profit facility, longer length of index hospital stay, and index hospitalizations that involved a surgical procedure. The 5-, 15-, and 30-day potentially avoidable readmission cumulative incidences were 6.0%, 15.1%, and 25.8%, respectively. CONCLUSION: Patients with end-stage kidney disease on maintenance hemodialysis are at high risk for 30-day readmission to hospital, with nearly three-quarters (70.1%) of all 30-day readmissions being potentially avoidable. Research is warranted to develop cost-effective and transferrable interventions that improve care transitions from hospital to outpatient hemodialysis facility and reduce readmission risk for this vulnerable population.

Incremental dialysis for preserving residual kidney function-Does one size fit all when initiating dialysis?

While many patients have substantial residual kidney function (RKF) when initiating hemodialysis (HD), most patients with end stage renal disease in the United States are initiated on 3-times per week conventional HD regimen, with little regard to RKF or patient preference. RKF is associated with many benefits including survival, volume control, solute clearance, and reduced inflammation. Several strategies have been recommended to preserve RKF after HD initiation, including an incremental approach to HD initiation. Incremental HD prescriptions are personalized to achieve adequate volume control and solute clearance with consideration to a patient's endogenous renal function. This allows the initial use of less frequent and/or shorter HD treatment sessions. Regular measurement of RKF is important because HD frequency needs to be increased as RKF inevitably declines. We narratively review the results of 12 observational cohort studies of twice-weekly compared to thrice-weekly HD. Incremental HD is associated with several benefits including preservation of RKF as well as extending the event-free life of arteriovenous fistulas and grafts. Patient survival and quality of life, however, has been variably associated with incremental HD. Serious risks must also be considered, including increased hospitalization and mortality perhaps related to fluid and electrolyte shifts after a long interdialytic interval. On the basis of the above literature review, and our clinical experience, we suggest patient characteristics which may predict favorable outcomes with an incremental approach to HD. These include substantial RKF, adequate volume control, lack of significant anemia/electrolyte imbalance, satisfactory health-related quality of life, low comorbid disease burden, and good nutritional status without evidence of hypercatabolism. Clinicians should engage patients in on-going conversations to prepare for incremental HD initiation and to ensure a smooth transition to thrice-weekly HD when needed.

Lung ultrasonography in end-stage renal disease: moving from evidence to practice-a narrative review.

Traditionally, point of care ultrasonography in nephrology has been used for renal biopsies and dialysis line placement. However, there is an emerging literature supporting the value of point of care lung ultrasonography in the assessment of volume status for dialysis patients. We conducted a review and identified 12 studies that examined the utility of lung ultrasonography in assessing volume status in patients with end-stage renal disease. We conclude that lung ultrasonography can be used to determine volume status in chronic dialysis patients by identifying lung congestion using the B-line score. Incorporating this technique into practice may have significant diagnostic and prognostic value for this high-risk population, as it provides the nephrologist with a useful bedside technique to assess extravascular lung water. Developing competence in lung ultrasonography is straightforward. The nephrology community should consider adding this useful tool into fellowship training, paralleling its broader use in other internal medicine specialties.

Barriers to Peritoneal Dialysis in Aboriginal Patients.

BACKGROUND: Aboriginal people in Canada have an unduly high burden of end-stage kidney disease (ESKD) and many live in rural settings. Peritoneal dialysis (PD) is a home-based dialysis modality that may provide a valuable alternative to in-center hemodialysis which is relatively underutilized by the Aboriginal population. OBJECTIVE: We aim to assess the barriers to PD utilization in Aboriginal patients with ESKD. DESIGN: This article is a prospective observational cohort study. SETTING: The setting involves 3 predialysis clinics in Winnipeg, Kingston, and Moose Factory. PATIENTS: The patients were 99 individuals (67 non-Aboriginal and 32 Aboriginal) who were at least 18 years of age with an estimated glomerular filtration rate of less than 30 mL/min/1.73m2, and were enrolled in one of the 3 study sites from April 2011 to October 2013. MEASUREMENTS: Patient demographics and comorbidities were documented. Barriers to PD, PD as modality choice, and Aboriginal status were assessed via patient survey upon study enrollment. PD use as the initial dialysis modality was assessed via monthly patient follow-up for 1 year after enrollment in the study. METHODS: The patient survey was created based on literature review of known barriers to PD, repaired based on direct patient feedback, and tested for reliability via the test-retest method. Differences in PD choice, barriers to PD, and PD use between Aboriginal and non-Aboriginal patients were determined by chi-square test and logistic regression. RESULTS: All patients enrolled in the study completed the survey. Mean age was 65.5 versus 54.6 years for non-Aboriginals and Aboriginals, respectively. Barriers to PD significantly associated with Aboriginal status were lack of money (odds ratio [OR]: 21.3; 95% confidence interval [CI]: 5.3-86.4; P < .0001) and anxiety (OR: 2.8; 95% CI: 1.1-7.1; P = .03). There was no difference in PD choice between non-Aboriginals and Aboriginals (66.7% vs 68.8%, respectively; P = .83). One of 67 non-Aboriginals (1.5%) and 5 of 32 Aboriginals (15.6%) died prior to initiating dialysis (P = .013). No significant difference was observed between non-Aboriginals (33%) and Aboriginals (28%) in use of PD (P = .81). LIMITATIONS: Small sample size was a limitation of this study. CONCLUSIONS: Aboriginal people in Canada have a disproportionately large burden of ESKD, and PD could provide an alternative to in-center hemodialysis for those living in rural areas. Our study identified anxiety and lack of money as barriers to PD significantly associated with Aboriginal status. When choosing dialysis modality, shared decision making between physicians and patient is of key importance to weigh all potential benefits and risks and emphasize the Aboriginal patient's values and preferences. These results can be used to guide future research and to help devise interventions targeting barriers to PD in Aboriginals.

CONTEXTE: Au Canada, un nombre important de personnes autochtones habitent en région rurale, et cette population présente un taux exagérément élevé d'insuffisance rénale terminale (IRT) par rapport à la population générale. La dialyse péritonéale (DP) est une modalité de dialyse que le patient reçoit à domicile et qui pourrait s'avérer une solution de remplacement intéressante à l'hémodialyse en centre, laquelle est relativement sous-utilisée par les patients autochtones. OBJECTIF DE L'ÉTUDE: Nous voulions recenser les facteurs qui restreignent l'utilisation de la DP chez les patients autochtones souffrant d'IRT. TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte observationnelle et prospective. CADRE DE L'ÉTUDE: Trois cliniques de prédialyse situées à Winnipeg, à Kingston et à Moose Factory ont pris part à l'étude. PATIENTS: La cohorte était constituée de 99 patients adultes (67 allochtones et 32 autochtones) dont le débit de filtration glomérulaire estimé (DFGe) était de moins de 30 ml/min/1,73 m2. Les participants à l'étude ont été recrutés parmi les patients des trois centres de prédialyse mentionnés ci-haut entre avril 2011 et octobre 2013. MESURES: On a d'abord noté les données démographiques et les comorbidités des patients. Ensuite, un sondage réalisé auprès des patients au moment du recrutement a permis d'établir leur statut autochtone ou allochtone, de déterminer les facteurs qui constituaient un frein à leur utilisation de la DP, de même que des données sur l'usage de la DP comme modalité de dialyse. Le choix de la DP comme modalité initiale a été déterminé par un suivi mensuel sur une période d'un an post-recrutement. MÉTHODOLOGIE: Les obstacles à l'utilisation de la DP comme modalité de dialyse figurant dans le sondage étaient basés sur une revue de la littérature recensant ces facteurs. Le sondage a ensuite été modifié en fonction de la rétroaction offerte par les patients, et sa fiabilité a été évaluée par la méthode du test-retest. Les divergences observées entre le choix ou non de la DP comme modalité de dialyse, les facteurs freinant son utilisation et les variations relevées en regard de l'origine ethnique des patients (autochtones ou allochtones) ont été établies par le test du chi carré et par régression logistique. RÉSULTATS: Tous les patients inclus dans l'étude ont répondu au sondage. L'âge moyen des patients allochtones était de 65,5 ans alors qu'il était de 54,6 ans pour les patients autochtones. Les entraves à l'utilisation de la DP associées de façon significative avec le statut d'autochtone étaient le manque d'argent (RC=21,3; IC 95% 5,3-86,4; p<0,0001) et l'anxiété (RC=2,8; IC 95 1,1-7,1; p=0,03). Aucune différence n'a été observée entre allochtones et autochtones (66,7 % contre 68,8 % respectivement; p=0,83) en ce qui concerne le choix de la DP comme modalité de dialyse. Un patient allochtone (1,5 %) et 5 patients autochtones (15,6 %) sont décédés au cours de la période couverte par l'étude. Enfin, aucune variation significative n'a été observée entre les patients autochtones et allochtones (28 % et 33 % respectivement; p=0,81) en regard de l'utilisation de la DP comme modalité de dialyse. LIMITES DE L'ÉTUDE: La taille restreinte de l'échantillon limite la portée de cette étude. CONCLUSION: Au Canada, l'insuffisance rénale terminale affecte les patients autochtones de façon disproportionnelle. Pour ceux d'entre eux qui habitent en région rurale, la dialyse péritonéale, qui se pratique à domicile, pourrait s'avérer une solution de remplacement intéressante à l'hémodialyse conventionnelle qui elle, se pratique en centre hospitalier. Notre étude a révélé que l'anxiété et le manque d'argent constituaient des facteurs restreignant l'utilisation de la DP chez la population autochtone. Dans le choix d'une modalité de dialyse, la prise de décision conjointe du patient avec les médecins revêt une importance majeure : d'abord pour bien mesurer les bienfaits et les risques potentiels, mais également pour tenir compte des valeurs et des préférences du patient autochtone. Ces résultats pourront servir à orienter les recherches futures et à concevoir des interventions ciblant les facteurs qui freinent l'utilisation de la DP chez les patients autochtones atteints d'IRT.

A brief review of intradialytic hypotension with a focus on survival.

Intradialytic hypotension (IDH), a common complication of ultrafiltration during hemodialysis therapy, is associated with high mortality and morbidity. IDH, defined as a nadir systolic blood pressure of less than 90 mm Hg on more than 30% of treatments, is a relevant definition and is correlated with mortality. Risk factors for IDH include patient demographics, anti-hypertensive medication use, larger interdialytic weight gain, and dialysis prescription features as dialysate sodium, high ultrafiltration rate, and dialysate temperature. A high frequency of IDH events carries a substantial death risk. An ultrafiltration rate >10 mL/h/kg, and even more so >13 mL/h/kg, is highly predictive of cardiovascular and all-cause mortality. Evidence suggests that IDH causes acute reversible segmental myocardial hypoperfusion and contractile dysfunction (myocardial stunning), which can result in long-term loss of myocardial contractility, leading to premature death. IDH also has negative end-organ effects on the brain and gut, contributing to mortality through stroke, and endotoxin translocation with associated inflammation and protein-energy wasting. Given strong association of IDH and dialysis mortality, a paradigm shift to its approach is urgently needed. Randomized controlled trials are required to prospectively test drugs and monitoring devices which may reduce IDH.

Changes in urine volume and serum albumin in incident hemodialysis patients.

INTRODUCTION: Hypoalbuminemia is a predictor of poor outcomes in dialysis patients. Among hemodialysis patients, there has not been prior study of whether residual kidney function or decline over time impacts serum albumin levels. We hypothesized that a decline in residual kidney function is associated with an increase in serum albumin levels among incident hemodialysis patients. METHODS: In a large national cohort of 38,504 patients who initiated hemodialysis during 1/2007-12/2011, we examined the association of residual kidney function, ascertained by urine volume and renal urea clearance, with changes in serum albumin over five years across strata of baseline residual kidney function, race, and diabetes using case-mix adjusted linear mixed effects models. FINDINGS: Serum albumin levels increased over time. At baseline, patients with greater urine volume had higher serum albumin levels: 3.44 ± 0.48, 3.50 ± 0.46, 3.57 ± 0.44, 3.59 ± 0.45, and 3.65 ± 0.46 g/dL for urine volume groups of <300, 300-<600, 600-<900, 900-<1,200, and ≥1,200 mL/day, respectively (Ptrend < 0.001). Over time, urine volume and renal urea clearance declined and serum albumin levels rose, while the baseline differences in serum albumin persisted across groups of urinary volume. In addition, the rate of decline in residual kidney function was not associated with the rate of change in albumin. DISCUSSION: Hypoalbuminemia in hemodialysis patients is associated with lower residual kidney function. Among incident hemodialysis patients, there is a gradual rise in serum albumin that is independent of the rate of decline in residual kidney function, suggesting that preservation of residual kidney function does not have a deleterious impact on serum albumin levels.

Preservation of residual kidney function in hemodialysis patients: reviving an old concept.

Residual kidney function (RKF) may confer a variety of benefits to patients on maintenance dialysis. RKF provides continuous clearance of middle molecules and protein-bound solutes. Whereas the definition of RKF varies across studies, interdialytic urine volume may emerge as a pragmatic alternative to more cumbersome calculations. RKF preservation is associated with better patient outcomes including survival and quality of life and is a clinical parameter and research focus in peritoneal dialysis. We propose the following practical considerations to preserve RKF, especially in newly transitioned (incident) hemodialysis patients: (1) periodic monitoring of RKF in hemodialysis patients through urine volume and including residual urea clearance with dialysis adequacy and outcome markers such as anemia, fluid gains, minerals and electrolytes, nutritional, status and quality of life; (2) avoidance of nephrotoxic agents such as radiocontrast dye, nonsteroidal anti-inflammatory drugs, and aminoglycosides; (3) more rigorous hypertension control and minimizing intradialytic hypotensive episodes; (4) individualizing the initial dialysis prescription with consideration of an incremental/infrequent approach to hemodialysis initiation (e.g., twice weekly) or peritoneal dialysis; and (5) considering a lower protein diet, especially on nondialysis days. Because RKF appears to be associated with better patient outcomes, it requires more clinical and research focus in the care of hemodialysis and peritoneal dialysis patients.

Residual Kidney Function Decline and Mortality in Incident Hemodialysis Patients.

In patients with ESRD, residual kidney function (RKF) contributes to achievement of adequate solute clearance. However, few studies have examined RKF in patients on hemodialysis. In a longitudinal cohort of 6538 patients who started maintenance hemodialysis over a 4-year period (January 2007 through December 2010) and had available renal urea clearance (CLurea) data at baseline and 1 year after hemodialysis initiation, we examined the association of annual change in renal CLurea rate with subsequent survival. The median (interquartile range) baseline value and mean±SD annual change of CLurea were 3.3 (1.9-5.0) and -1.1±2.8 ml/min per 1.73 m2, respectively. Greater CLurea rate 1 year after hemodialysis initiation associated with better survival. Furthermore, we found a gradient association between loss of RKF and all-cause mortality: changes in CLurea rate of -6.0 and +3.0 ml/min per 1.73 m2 per year associated with case mix-adjusted hazard ratios (95% confidence intervals) of 2.00 (1.55 to 2.59) and 0. 61 (0.50 to 0.74), respectively (reference: -1.5 ml/min per 1.73 m2 per year). These associations remained robust against adjustment for laboratory variables and ultrafiltration rate and were consistent across strata of baseline CLurea, age, sex, race, diabetes status, presence of congestive heart failure, and hemoglobin, serum albumin, and serum phosphorus levels. Sensitivity analyses using urine volume as another index of RKF yielded consistent associations. In conclusion, RKF decline during the first year of dialysis has a graded association with all-cause mortality among incident hemodialysis patients. The clinical benefits of RKF preservation strategies on mortality should be determined.

Incremental Hemodialysis, Residual Kidney Function, and Mortality Risk in Incident Dialysis Patients: A Cohort Study.

BACKGROUND: Maintenance hemodialysis is typically prescribed thrice weekly irrespective of a patient's residual kidney function (RKF). We hypothesized that a less frequent schedule at hemodialysis therapy initiation is associated with greater preservation of RKF without compromising survival among patients with substantial RKF. STUDY DESIGN: A longitudinal cohort. SETTING & PARTICIPANTS: 23,645 patients who initiated maintenance hemodialysis therapy in a large dialysis organization in the United States (January 2007 to December 2010), had available RKF data during the first 91 days (or quarter) of dialysis, and survived the first year. PREDICTOR: Incremental (routine twice weekly for >6 continuous weeks during the first 91 days upon transition to dialysis) versus conventional (thrice weekly) hemodialysis regimens during the same time. OUTCOMES: Changes in renal urea clearance and urine volume during 1 year after the first quarter and survival after the first year. RESULTS: Among 23,645 included patients, 51% had substantial renal urea clearance (≥3.0mL/min/1.73m(2)) at baseline. Compared with 8,068 patients with conventional hemodialysis regimens matched based on baseline renal urea clearance, urine volume, age, sex, diabetes, and central venous catheter use, 351 patients with incremental regimens exhibited 16% (95% CI, 5%-28%) and 15% (95% CI, 2%-30%) more preserved renal urea clearance and urine volume at the second quarter, respectively, which persisted across the following quarters. Incremental regimens showed higher mortality risk in patients with inadequate baseline renal urea clearance (≤3.0mL/min/1.73m(2); HR, 1.61; 95% CI, 1.07-2.44), but not in those with higher baseline renal urea clearance (HR, 0.99; 95% CI, 0.76-1.28). Results were similar in a subgroup defined by baseline urine volume of 600mL/d. LIMITATIONS: Potential selection bias and wide CIs. CONCLUSIONS: Among incident hemodialysis patients with substantial RKF, incremental hemodialysis may be a safe treatment regimen and is associated with greater preservation of RKF, whereas higher mortality is observed after the first year of dialysis in those with the lowest RKF. Clinical trials are needed to examine the safety and effectiveness of twice-weekly hemodialysis.

Reducing hospital readmissions in patients with end-stage kidney disease.

ESKD patients have a large burden of disease, with high rates of readmission to hospital compared with the general population. A readmission after an acute index hospital discharge is either planned or unplanned. A proportion of unplanned readmissions are potentially avoidable, and could have been prevented with optimized transitional care. Readmissions pose financial cost to the health care system and emotional cost to patients and caregivers. In other chronic diseases with high readmission risk, such as congestive heart failure, interventions have improved transitional care and reduced readmission risk. In reviewing the existing literature on readmissions in ESKD, the definition and risk of readmission varied widely by study, with many potentially associated factors including comorbid diseases such as anemia and hypoalbuminemia. An ESKD patient's requisite follow-up in the outpatient dialysis facility provides an opportunity to improve transitional care at the time of discharge. Despite this, our review of existing literature found no studies which have tested interventions to reduce the risk of readmission in ESKD patients. We propose a framework to define the determinants of avoidable readmission in ESKD, and use this framework to define a research agenda. Avoidable readmissions in ESKD patients is a topic prime for in-depth study, given the high-risk nature in this patient population, financial and societal costs, and potential for risk modification through targeted interventions.

Outcomes following Kidney transplantation in IgA nephropathy: a UNOS/OPTN analysis.

This study updates assessment of post-transplant outcomes in IgAN patients in the modern era of immunosuppression. Using UNOS/OPTN data, patients ≥18 yr of age with first kidney transplant (1/1/1999 to 12/31/2008) were analyzed. Multivariable Cox regression models and propensity score-based matching techniques were used to estimate hazard ratios (HRs) for death-censored allograft survival (DCGS) and patient survival in IgAN compared to non-IgAN. Results of multivariable regression were stratified by donor type (living vs. deceased). A total of 107, 747 recipients were included (4589 with IgAN and 103 158 with non-IgAN). Adjusted HR for DCGS showed no significant difference between IgAN and non-IgAN. IgAN had higher patient survival compared to non-IgAN (HR 0.54, 95% CI 0.47-0.62, p < 0.0001 for deceased donors; HR 0.42, 95% CI 0.33-0.54, p < 0.0001 for living donors). Propensity score-matched analysis was similar, with no significant difference in DCGS between matched groups and higher patient survival in IgAN patients compared to non-IgAN group (HR 0.54, 95% CI 0.47, 0.63; p-value <0.0001). IgAN patients with first kidney transplant have superior patient survival and similar graft survival compared to non-IgAN recipients. Results can be used in prognostication and informed decision-making about kidney transplantation in patients with IgAN.

Challenges and opportunities in late-stage chronic kidney disease.

There is increasing recognition that chronic diseases are a major challenge for health delivery systems and treasuries. These are highly prevalent and costly diseases and frequency is expected to increase greatly as the population of many countries ages. Chronic kidney disease (CKD) has not received the same attention as other chronic diseases such as congestive heart failure; yet, the prevalence and costs of CKD are substantial. Greater recognition and support for CKD may require that the disease no longer be viewed as one continuous disease state. Early CKD stages require less complex care and generate lower costs. In contrast, late-stage CKD is every bit as complex and costly as other major chronic diseases. Health authorities may not recognize and fund CKD care appropriately until late-stage CKD is defined clearly as separate and distinct from earlier stages of disease. In this review, we describe the burden of chronic diseases, consider the challenges and barriers and propose processes to improve late-stage CKD care. In particular, we recommend the need for improved continuity of care, enhanced use of information technology, multidisciplinary care, timely referral to nephrologists, protocol use and improved patient engagement.

Increasing hip fractures in patients receiving hemodialysis and peritoneal dialysis.

BACKGROUND/AIMS: Dialysis patients are at increased risk for hip fractures. Because changes in treatment of metabolic bone disease in this population may have impacted bone fragility, this study aims to analyze the longitudinal risk for fractures in hemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: Using the United States Renal Data System database from 1992 to 2009, the temporal trend in hip fractures requiring hospitalization was analyzed using an overdispersed Poisson regression model. Generalized Estimating Equations were used to assess the adjusted effect of dialysis modality on hip fractures. RESULTS: 842,028 HD and 87,086 PD patients were included. There was a significant temporal increase in hip fractures in both HD and PD with stabilization of rates after 2005. With stratification, the increase in fractures occurred in patients who were white and over 65 years of age. In adjusted analyses, HD patients had 1.6 times greater odds of hip fracture than PD patients (OR 1.60 95% CI 1.52, 1.68, p < 0.001). CONCLUSIONS: In contrast to the declining hip fracture rates in the general population, we identified a temporal rise in incidence of hip fractures in HD and PD patients. HD patients were at a higher risk for hip fractures than PD patients after adjustment for recognized bone fragility risk factors. The increase in fracture rate over time was limited to older white patients in both HD and PD, the demographics being consistent with osteoporosis risk. Further research is indicated to better understand the longitudinal trend in hip fractures and the discordance between HD and PD.

Increased bone fractures among elderly United States hemodialysis patients.

BACKGROUND: Fractures are an important cause of morbidity in hemodialysis patients. Multiple advances in the treatment of mineral and bone disease in hemodialysis patients have occurred. The purpose of this study was to determine whether the rate of fractures in hemodialysis patients has changed over time. METHODS: We studied US Renal Data System (USRDS) datasets to determine the rates of hospitalized fractures among hemodialysis patients. The primary outcome was incidence of fractures requiring hospitalization. The fracture rate per 1000 person-years was calculated by year from 1992 to 2009. The first 90 days after initiating dialysis were excluded from analysis. RESULTS: The incidence of hip and vertebral fractures increased from 12.5 fractures per 1000 patient-years in 1992 to 25.3 per 1000 patient-years in 2004 (P < 0.0001). Arm and leg fractures increased from 3.2 per 1000 patient-years in 1992 to 7.7 per 1000 patient-years in 2009 (P < 0.0001). The greatest increase in hip and verterbral fracture rate was seen in white patients >65 years of age. After 2004, the incidence rate of these fractures stabilized and subtly declined, but did not decrease significantly. CONCLUSIONS: Fracture rates increased significantly in hemodialysis patients from 1992 to 2004, with most of the increase occurring in elderly white patients. Assessment of fracture risk and management in dialysis patients at greatest risk requires greater emphasis and further study.