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Abstract Background Abdominal aortic aneurysms (AAA) are local dilatations of the infrarenal aorta. If left untreated they may rupture and lead to death. One form of treatment is the minimally invasive insertion of a stent-graft into the aneurysm. Despite this effective treatment aneurysms may occasionally continue to expand and this may eventually result in post-operative rupture of the aneurysm. Fluid-structure interaction (FSI) is a particularly useful tool for investigating aneurysm biomechanics as both the wall stresses and fluid forces can be examined. Methods Pre-op, Post-op and Follow-up models were reconstructed from CT scans of a single patient and FSI simulations were performed on each model. The FSI approach involved coupling Abaqus and Fluent via a third-party software - MpCCI. Aneurysm wall stress and compliance were investigated as well as the drag force acting on the stent-graft. Results Aneurysm wall stress was reduced from 0.38 MPa before surgery to a value of 0.03 MPa after insertion of the stent-graft. Higher stresses were seen in the aneurysm neck and iliac legs post-operatively. The compliance of the aneurysm was also reduced post-operatively. The peak Post-op axial drag force was found to be 4.85 N. This increased to 6.37 N in the Follow-up model. Conclusion In a patient-specific case peak aneurysm wall stress was reduced by 92%. Such a reduction in aneurysm wall stress may lead to shrinkage of the aneurysm over time. Hence, post-operative stress patterns may help in determining the likelihood of aneurysm shrinkage post EVAR. Post-operative remodelling of the aneurysm may lead to increased drag forces.

Background: Humans are exposed to uranium (U) in a variety of applications. Both animal and observational human studies support an associated U nephrotoxicity. Few statistical syntheses of the human data have been performed and these analyses are limited in the types of exposures considered., Objectives: This study aims to evaluate the state of current evidence and to expand on existing meta-analyses by systematically evaluating kidney-associated causes of mortality in multiple U-exposed populations. This study also aims to evaluate the effect of U exposure on kidney function and biomarkers of kidney injury., Methods: The published and grey literature were systematically reviewed for studies that reported Standardized Mortality Ratios (SMR) for kidney cancer, chronic nephritis/nephrosis, all-cause mortality, diabetes, all circulatory/heart disease, and/or ischemic heart disease in U-exposed humans. Studies that reported kidney biomarker measures for U-exposed versus control subjects were identified separately., Results: 36 studies were included. The studies were parsed into subgroups based on setting of exposure. Analysis of kidney cancer and chronic nephritis/nephrosis mortality demonstrated an SMR of 0.93 (95CI: 0.82-1.05) and 0.82 (95CI: 0.70-0.96), respectively. The other clinical outcomes evaluated also demonstrated mortality deficits in exposed relative to unexposed individuals. Subgroup analyses demonstrated similar mortality deficits. Conversely, biomarker analyses suggested better kidney function in the controls, but none of these differences reached significance., Discussion: Given that most of the included mortality studies were conducted in occupational populations, the mortality deficits observed in our analyses were likely due to the healthy-worker effect. Additionally, our analyses of kidney biomarkers were severely limited by low precision due to a low number of available studies and small study-size. Future work needs to evaluate the progression of chronic and to end-stage kidney disease in community-based populations to better assess the full impact of prolonged chronic U exposure on kidney outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: IgA nephropathy (IgAN) is the most common primary glomerular disease, with approximately 20% to 40% of patients progressing to kidney failure within 25 years. Non-immunosuppressive treatment has become a mainstay in the management of IgAN by improving blood pressure (BP) management, decreasing proteinuria, and avoiding the risks of long-term immunosuppressive management. Due to the slowly progressive nature of the disease, clinical trials are often underpowered, and conflicting information about management with non-immunosuppressive treatment is common. This is an update of a Cochrane review, first published in 2011., Objectives: To assess the benefits and harms of non-immunosuppressive treatment for treating IgAN in adults and children. We aimed to examine all non-immunosuppressive therapies (e.g. anticoagulants, antihypertensives, dietary restriction and supplementation, tonsillectomy, and herbal medicines) in the management of IgAN., Search Methods: We searched the Cochrane Kidney and Transplant Register of Studies up to December 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov., Selection Criteria: Randomised controlled trials (RCTs) and quasi-RCTs of non-immunosuppressive agents in adults and children with biopsy-proven IgAN were included., Data Collection and Analysis: Two authors independently reviewed search results, extracted data and assessed study quality. Results were expressed as mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI) using random-effects meta-analysis. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Main Results: This review includes 80 studies (4856 participants), of which 24 new studies (2018 participants) were included in this review update. The risk of bias within the included studies was mostly high or unclear for many of the assessed methodological domains, with poor reporting of important key clinical trial methods in most studies. Antihypertensive therapies were the most examined non-immunosuppressive therapy (37 studies, 1799 participants). Compared to placebo or no treatment, renin-angiotensin system (RAS) inhibition probably decreases proteinuria (3 studies, 199 participants: MD - 0.71 g/24 h, 95% CI -1.04 to -0.39; moderate certainty evidence) but may result in little or no difference to kidney failure or doubling of serum creatinine (SCr), or complete remission of proteinuria (low certainty evidence). Death, remission of haematuria, relapse of proteinuria or > 50% increase in SCr were not reported. Compared to symptomatic treatment, RAS inhibition (3 studies, 168 participants) probably decreases proteinuria (MD -1.16 g/24 h, 95% CI -1.52 to -0.81) and SCr (MD -9.37 µmol/L, 95% CI -71.95 to -6.80) and probably increases creatinine clearance (2 studies, 127 participants: MD 23.26 mL/min, 95% CI 10.40 to 36.12) (all moderate certainty evidence); however, the risk of kidney failure is uncertain (1 study, 34 participants: RR 0.20, 95% CI 0.01 to 3.88; very low certainty evidence). Death, remission of proteinuria or haematuria, or relapse of proteinuria were not reported. The risk of adverse events may be no different with RAS inhibition compared to either placebo or symptomatic treatment (low certainty evidence). In low certainty evidence, tonsillectomy in people with IgAN in addition to standard care may increase remission of proteinuria compared to standard care alone (2 studies, 143 participants: RR 1.90, 95% CI 1.45 to 2.47) and remission of microscopic haematuria (2 studies, 143 participants: RR 1.93, 95% CI 1.47 to 2.53) and may decrease relapse of proteinuria (1 study, 73 participants: RR 0.70, 95% CI 0.57 to 0.85) and relapse of haematuria (1 study, 72 participants: RR 0.70, 95% CI 0.51 to 0.98). Death, kidney failure and a > 50% increase in SCr were not reported. These trials have only been conducted in Japanese people with IgAN, and the findings' generalisability is unclear. Anticoagulant therapy, fish oil, and traditional Chinese medicines exhibited small benefits to kidney function in patients with IgAN when compared to placebo or no treatment. However, compared to standard care, the kidney function benefits are no longer evident. Antimalarial therapy compared to placebo in one study reported an increase in a > 50% reduction of proteinuria (53 participants: RR 3.13 g/24 h, 95% CI 1.17 to 8.36; low certainty evidence). Although, there was uncertainty regarding adverse events from this study due to very few events., Authors' Conclusions: Available RCTs focused on a diverse range of interventions. They were few, small, and of insufficient duration to determine potential long-term benefits on important kidney and cardiovascular outcomes and harms of treatment. Antihypertensive agents appear to be the most beneficial non-immunosuppressive intervention for IgAN. The antihypertensives examined were predominantly angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The benefits of RAS inhibition appear to outweigh the harms in patients with IgAN. The certainty of the evidence of RCTs demonstrating a benefit of tonsillectomy to patients with Japanese patients with IgAN was low. In addition, these findings are inconsistent across observational studies in people with IgAN of other ethnicities; hence, tonsillectomy is not widely recommended, given the potential harm of therapy. The RCT evidence is insufficiently robust to demonstrate efficacy for the other non-immunosuppressive treatments evaluated here., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Source Citation: Meekers E, Dauw J, Martens P, et al. Renal function and decongestion with acetazolamide in acute decompensated heart failure: the ADVOR trial. Eur Heart J. 2023;44:3672-3682. 37623428., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J23-0111.

Source Citation: Butler J, Packer M, Siddiqi TJ, et al. Efficacy of empagliflozin in patients with heart failure across kidney risk categories. J Am Coll Cardiol. 2023;81:1902-1914. 37164523., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J23-0065.

Source Citation: Azizi M, Saxena M, Wang Y, et al; RADIANCE II Investigators and Collaborators. Endovascular ultrasound renal denervation to treat hypertension: the RADIANCE II randomized clinical trial. JAMA. 2023;329:651-661. 36853250., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J23-0040.

Source Citation: Navaneethan SD, Zoungas S, Caramori ML, et al. Diabetes management in chronic kidney disease: synopsis of the KDIGO 2022 clinical practice guideline update. Ann Intern Med. 2023;176:381-387. 36623286., Competing Interests: Disclosures: The commentators have reported no disclosures of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J23-0023.

Purpose: To evaluate student perception of integrating biomedical and clinical sciences based on survey of dental students on the concurrent teaching of a didactic systems-based course and a case-based course., Methods: First-year to fourth-year students (DS1-DS4) students were surveyed for their experiences in concurrent teaching. Student response rate for the survey was 55% (229/420). Pearson's Chi-squared tests and Kruskal-Wallis rank sum tests were used to assess statistical significance (p < 0.05)., Results: Of the students surveyed, 83% strongly agreed or agreed that concurrent teaching of the didactic and case-based courses helped them better understand the biomedical science background and the clinical ramifications (p < 0.001). On average, 75% percent strongly agreed or agreed that concurrent teaching kept them engaged, motivated, think critically, apply the course content and prepare for clinical practice (p < 0.001). Of the students surveyed, 69% support expanding concurrent teaching to all four years (p < 0.001). Mean responses from DS1 and DS4 students differed for questions relating to understanding of biomedical sciences, critical thinking and application to clinic (p < 0.01). Qualitative data showed that students enjoyed the reinforcement of concepts and application to clinical scenarios., Conclusions: Concurrent teaching of didactic and case-based learning courses, thus showing clinical relevance of biomedical sciences in the first year of dental curriculum, is perceived by students as an effective method of educating dental students. Such integrative learning process with horizontal and vertical integration and concurrent curriculum is even more relevant with the implementation of the integrated national board dental examination., (© 2022 American Dental Education Association.)

Background: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited treatment options. Autologous hematopoietic stem cell transplantation (HSCT) has emerged as a potential intervention for severe SSc refractory to conventional treatment., Objectives: To assess the benefits and harms of autologous hematopoietic stem cell transplantation for the treatment of systemic sclerosis (specifically, non-selective myeloablative HSCT versus cyclophosphamide; selective myeloablative HSCT versus cyclophosphamide; non-selective non-myeloablative HSCT versus cyclophosphamide)., Search Methods: We searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE, Embase, and trial registries from database insertion to 4 February 2022., Selection Criteria: We included RCTs that compared HSCT to immunomodulators in the treatment of SSc., Data Collection and Analysis: Two review authors independently selected studies for inclusion, extracted study data, and performed risk of bias and GRADE assessments to assess the certainty of evidence using standard Cochrane methods., Main Results: We included three RCTs evaluating: non-myeloablative non-selective HSCT (10 participants), non-myeloablative selective HSCT (79 participants), and myeloablative selective HSCT (36 participants). The comparator in all studies was cyclophosphamide (123 participants). The study examining non-myeloablative non-selective HSCT had a high risk of bias given the differences in baseline characteristics between the two arms. The other studies had a high risk of detection bias for participant-reported outcomes. The studies had follow-up periods of one to 4.5 years. Most participants had severe disease, mean age 40 years, and the duration of disease was less than three years. Efficacy No study demonstrated an overall mortality benefit of HSCT when compared to cyclophosphamide. However, non-myeloablative selective HSCT showed overall survival benefits using Kaplan-Meier curves at 10 years and myeloablative selective HSCT at six years. We graded our certainty of evidence as moderate for non-myeloablative selective HSCT and myeloablative selective HSCT. Certainty of evidence was low for non-myeloablative non-selective HSCT. Event-free survival was improved compared to cyclophosphamide with non-myeloablative selective HSCT at 48 months (hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.16 to 0.74; moderate-certainty evidence). There was no improvement with myeloablative selective HSCT at 54 months (HR 0.54 95% CI 0.23 to 1.27; moderate-certainty evidence). The non-myeloablative non-selective HSCT trial did not report event-free survival. There was improvement in functional ability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI, scale from 0 to 3 with 3 being very severe functional impairment) with non-myeloablative selective HSCT after two years with a mean difference (MD) of -0.39 (95% CI -0.72 to -0.06; absolute treatment benefit (ATB) -13%, 95% CI -24% to -2%; relative percent change (RPC) -27%, 95% CI -50% to -4%; low-certainty evidence). Myeloablative selective HSCT demonstrated a risk ratio (RR) for improvement of 3.4 at 54 months (95% CI 1.5 to 7.6; ATB -37%, 95% CI -18% to -57%; RPC -243%, 95% CI -54% to -662%; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 9; low-certainty evidence). The non-myeloablative non-selective HSCT trial did not report HAQ-DI results. All transplant modalities showed improvement of modified Rodnan skin score (mRSS) (scale from 0 to 51 with the higher number being more severe skin thickness) favoring HSCT over cyclophosphamide. At two years, non-myeloablative selective HSCT showed an MD in mRSS of -11.1 (95% CI -14.9 to -7.3; ATB -22%, 95% CI -29% to -14%; RPC -43%, 95% CI -58% to -28%; moderate-certainty evidence). At 54 months, myeloablative selective HSCT at showed a greater improvement in skin scores than the cyclophosphamide group (RR 1.51, 95% CI 1.06 to 2.13; ATB -27%, 95% CI -6% to -47%; RPC -51%, 95% CI -6% to -113%; moderate-certainty evidence). The NNTB was 4 (95% CI 3 to 18). At one year, for non-myeloablative non-selective HSCT the MD was -16.00 (95% CI -26.5 to -5.5; ATB -31%, 95% CI -52% to -11%; RPC -84%, 95% CI -139% to -29%; low-certainty evidence). No studies reported data on pulmonary arterial hypertension. Adverse events In the non-myeloablative selective HSCT study, there were 51/79 serious adverse events with HSCT and 30/77 with cyclophosphamide (RR 1.7, 95% CI 1.2 to 2.3), with an absolute risk increase of 26% (95% CI 10% to 41%), and a relative percent increase of 66% (95% CI 20% to 129%). The number needed to treat for an additional harmful outcome was 4 (95% CI 3 to 11) (moderate-certainty evidence). In the myeloablative selective HSCT study, there were similar rates of serious adverse events between groups (25/34 with HSCT and 19/37 with cyclophosphamide; RR 1.43, 95% CI 0.99 to 2.08; moderate-certainty evidence). The non-myeloablative non-selective HSCT trial did not clearly report serious adverse events., Authors' Conclusions: Non-myeloablative selective and myeloablative selective HSCT had moderate-certainty evidence for improvement in event-free survival, and skin thicknesscompared to cyclophosphamide. There is also low-certainty evidence that these modalities of HSCT improve physical function. However, non-myeloablative selective HSCT and myeloablative selective HSCT resulted in more serious adverse events than cyclophosphamide; highlighting the need for careful risk-benefit considerations for people considering these HSCTs. Evidence for the efficacy and adverse effects of non-myeloablative non-selective HSCT is limited at this time. Due to evidence provided from one study with high risk of bias, we have low-certainty evidence that non-myeloablative non-selective HSCT improves outcomes in skin scores, forced vital capacity, and safety. Two modalities of HSCT appeared to be a promising treatment option for SSc though there is a high risk of early treatment-related mortality and other adverse events. Additional research is needed to determine the effectiveness and adverse effects of non-myeloablative non-selective HSCT in the treatment of SSc. Also, more studies will be needed to determine how HSCT compares to other treatment options such as mycophenolate mofetil, as cyclophosphamide is no longer the first-line treatment for SSc. Finally, there is a need for a greater understanding of the role of HSCT for people with SSc with significant comorbidities or complications from SSc that were excluded from the trial criteria., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Source Citation: Drekonja DM, Trautner B, Amundson C, et al. Effect of 7 vs 14 days of antibiotic therapy on resolution of symptoms among afebrile men with urinary tract infection: a randomized clinical trial. JAMA. 2021;326:324-31. 34313686.

Source Citation: Jayne DRW, Merkel PA, Schall TJ, et al. Avacopan for the treatment of ANCA-associated vasculitis. N Engl J Med. 2021;384:599-609. 33596356.

Objective: This study assessed stent healing patterns and cardiovascular outcomes by optical coherence tomography (OCT) in cancer patients after drug-eluting stent (DES) placement. Background: Cancer treatment, owing to its cytotoxic and antiproliferative effects, could delay stent healing and increase stent thrombosis risk, especially when dual antiplatelet therapy (DAPT) is discontinued early for oncological treatment. OCT can assess stent endothelialization and other healing parameters, which may provide clinical guidance in these challenging scenarios. Methods: This single-center retrospective study enrolled all cancer patients who underwent OCT for assessment of vascular healing patterns after prior DES placement from November 2009 to November 2018. Primary study endpoints were stent healing parameters, including stent coverage, apposition, degree of expansion, neointimal hyperplasia heterogeneity, in-stent restenosis, stent thrombosis, and overall survival (OS). Results: A total of 67 patients were included in this study. Mean time between DES placement and OCT evaluation was 154 ± 82 days. Stent healing matched published values for DES in non-cancer patients ( P ≥ 0.063). At 1 year, the OS was 86% (95% confidence interval [CI]: 78-96%) with 0% incidence of acute coronary syndrome. Advanced cancers and active chemotherapies were associated with inferior OS ( P = 0.024, hazard ratio [HR]: 3.50, 95% CI: 1.18-10.42 and P = 0.026, HR: 2.65, 95% CI: 1.13-6.22, respectively), while stent healing parameters were unassociated with OS. Forty-one patients (61%) had DAPT duration ≤6 months. Conclusions: Stent healing of contemporary DES appears similar in cancer and non-cancer patients. Cardiovascular risk of cancer patients after DES placement can be managed to facilitate timely cancer therapies, as the underlying malignancy and active chemotherapy ultimately determine survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Aziz, Herrmann, Marmagkiolis, Balanescu, Donisan, Pushparaji, Lin, Tomakin, Hoyt, Pham, Dijkstra, Cilingiroglu, Lopez-Mattei, Zaha, Anderson, Feldman, Molony and Iliescu.)

Source Citation: Heerspink HJ, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383:1436-46. 32970396.

Background: Combination therapy with multiple phosphate binders is prescribed to reduce elevated serum phosphorus (sP) concentrations among patients on maintenance hemodialysis. Sucroferric oxyhydroxide (SO), an iron-based phosphate binder, has demonstrated efficacy at reducing sP while also being associated with a low pill burden. Whereas the effects of SO monotherapy have been well characterized in clinical trials and observational cohorts, little is known about the effects of SO-containing combination therapy., Methods: Patients on hemodialysis ( N =234) at Fresenius Kidney Care (FKC) who received ≥120 days of uninterrupted phosphate binder combination therapy with SO were included in this retrospective study. Patient data were censored after SO discontinuation, end of care at FKC, or completion of 12 months of follow-up. Quarterly (Q) changes in phosphate binder pill burden, mean sP, and proportion of patients achieving National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI)-recommended sP levels (≤5.5 mg/dl) were compared between baseline (-Q1) and follow-up (Q1-Q4)., Results: Phosphate binder combination therapy with SO was associated with significant increase in the proportion of patients with sP ≤5.5 mg/dl (from 19% at baseline to up to 40% at follow-up; P <0.001) and reduction in sP at all postbaseline time points (from 6.7 mg/dl to 6.2-6.3 mg/dl; P <0.001). Patients on calcium acetate ( N =54) and sevelamer ( N =94) who added SO therapy at follow-up resulted in a ≥250% increase in patients achieving sP ≤5.5 mg/dl (all P <0.001). Whereas mean phosphate binder pill burden increased with initiation of phosphate binder combination therapy with SO (15.8 pills/d at Q1 versus 12.3 pills/d at -Q1), continued use of SO was associated with down-titration of non-SO phosphate binders such that, by Q4, mean total PB pill burden reduced to 12.3 pills/d., Conclusions: For patients on hemodialysis with uncontrolled hyperphosphatemia, combination therapy with SO may allow for sustained improvements in sP control without adversely affecting phosphate binder pill burden., Competing Interests: L. Ficociello, R. Kossmann, C. Mullon, and V. Parameswaran are employees of Fresenius Medical Care Renal Therapies Group. R. Kossmann and C. Mullon own stock in Fresenius Medical Care North America. R. Kossmann is on the board of directors of Advanced Renal Technologies. D. Molony is professor of medicine at the McGovern Medical School, University of Texas Houston, and reports personal fees from Fresenius Medical Care outside the submitted work., (Copyright © 2020 by the American Society of Nephrology.)

Background: IgA nephropathy is the most common glomerulonephritis world-wide. IgA nephropathy causes end-stage kidney disease (ESKD) in 15% to 20% of affected patients within 10 years and in 30% to 40% of patients within 20 years from the onset of disease. This is an update of a Cochrane review first published in 2003 and updated in 2015., Objectives: To determine the benefits and harms of immunosuppression strategies for the treatment of IgA nephropathy., Search Methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 9 September 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov., Selection Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs of treatment for IgA nephropathy in adults and children and that compared immunosuppressive agents with placebo, no treatment, or other immunosuppressive or non-immunosuppressive agents., Data Collection and Analysis: Two authors independently assessed study risk of bias and extracted data. Estimates of treatment effect were summarised using random effects meta-analysis. Treatment effects were expressed as relative risk (RR) and 95% confidence intervals (95% CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Risks of bias were assessed using the Cochrane tool. Evidence certainty was evaluated using GRADE methodology., Main Results: Fifty-eight studies involving 3933 randomised participants were included. Six studies involving children were eligible. Disease characteristics (kidney function and level of proteinuria) were heterogeneous across studies. Studies evaluating steroid therapy generally included patients with protein excretion of 1 g/day or more. Risk of bias within the included studies was generally high or unclear for many of the assessed methodological domains. In patients with IgA nephropathy and proteinuria > 1 g/day, steroid therapy given for generally two to four months with a tapering course probably prevents the progression to ESKD compared to placebo or standard care (8 studies; 741 participants: RR 0.39, 95% CI 0.23 to 0.65; moderate certainty evidence). Steroid therapy may induce complete remission (4 studies, 305 participants: RR 1.76, 95% CI 1.03 to 3.01; low certainty evidence), prevent doubling of serum creatinine (SCr) (7 studies, 404 participants: RR 0.43, 95% CI 0.29 to 0.65; low certainty evidence), and may lower urinary protein excretion (10 studies, 705 participants: MD -0.58 g/24 h, 95% CI -0.84 to -0.33;low certainty evidence). Steroid therapy had uncertain effects on glomerular filtration rate (GFR), death, infection and malignancy. The risk of adverse events with steroid therapy was uncertain due to heterogeneity in the type of steroid treatment used and the rarity of events. Cytotoxic agents (azathioprine (AZA) or cyclophosphamide (CPA) alone or with concomitant steroid therapy had uncertain effects on ESKD (7 studies, 463 participants: RR 0.63, 95% CI 0.33 to 1.20; low certainty evidence), complete remission (5 studies; 381 participants: RR 1.47, 95% CI 0.94 to 2.30; very low certainty evidence), GFR (any measure), and protein excretion. Doubling of serum creatinine was not reported. Mycophenolate mofetil (MMF) had uncertain effects on the progression to ESKD, complete remission, doubling of SCr, GFR, protein excretion, infection, and malignancy. Death was not reported. Calcineurin inhibitors compared with placebo or standard care had uncertain effects on complete remission, SCr, GFR, protein excretion, infection, and malignancy. ESKD and death were not reported. Mizoribine administered with renin-angiotensin system inhibitor treatment had uncertain effects on progression to ESKD, complete remission, GFR, protein excretion, infection, and malignancy. Death and SCr were not reported. Leflunomide followed by a tapering course with oral prednisone compared to prednisone had uncertain effects on the progression to ESKD, complete remission, doubling of SCr, GFR, protein excretion, and infection. Death and malignancy were not reported. Effects of other immunosuppressive regimens (including steroid plus non-immunosuppressive agents or mTOR inhibitors) were inconclusive primarily due to insufficient data from the individual studies in low or very low certainty evidence. The effects of treatments on death, malignancy, reduction in GFR at least of 25% and adverse events were very uncertain. Subgroup analyses to determine the impact of specific patient characteristics such as ethnicity or disease severity on treatment effectiveness were not possible., Authors' Conclusions: In moderate certainty evidence, corticosteroid therapy probably prevents decline in GFR or doubling of SCr in adults and children with IgA nephropathy and proteinuria. Evidence for treatment effects of immunosuppressive agents on death, infection, and malignancy is generally sparse or low-quality. Steroid therapy has uncertain adverse effects due to a paucity of studies. Available studies are few, small, have high risk of bias and generally do not systematically identify treatment-related harms. Subgroup analyses to identify specific patient characteristics that might predict better response to therapy were not possible due to a lack of studies. There is no evidence that other immunosuppressive agents including CPA, AZA, or MMF improve clinical outcomes in IgA nephropathy., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

The optimal translation of evidence into the clinical practice of nephrology follows validated evidence-based medicine (EBM) principles. Most importantly, the evidence-based medicine practitioner requires that the evidence, as much as possible, addresses in an unbiased manner clinical questions of importance to patients and reflects the truth. In this chapter, we evaluate how cognitive biases that affect medical decision making might systematically bias the overall management of patients with kidney disease and, thus, distort the observations about disease causation, prognosis, diagnosis, and management that are derived from analysis of administrative databases or electronic medical records of health care systems. These cognitive biases influence how questions are framed, how risk factors and health status are measured, how decisions are made, and what actions are implemented. We explore the nature of these biases and the possible places where such biases are most likely to distort clinical care and the collection of the data that is used to inform clinical practice in nephrology. To the extent that cognitive biases selectively modify diagnostic interrogations and therapeutic interventions in some patients, the resultant databases may provide a skewed picture of the health of the nephrology patient population and should be considered with some skepticism when exploited to achieve best practice., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Children are increasingly being diagnosed with primary hypertension. The absence of comparative effectiveness research of antihypertensive medications in children has contributed to considerable differences in prescribing practices among physicians treating children with primary hypertension. Even if parallel-group trials had established a best overall choice for most of these children, the best medication for an individual may differ from the best overall medication., Methods/design: This project consists of a series of systematically administered n-of-1 trials among older children to verify the need for ongoing antihypertensive treatment and, if so, to identify the preferred single drug therapy from among the three major classes of drugs commonly used for primary hypertension (angiotensin-converting enzyme inhibitors, calcium channel blockers, and diuretics). We will determine whether one of these is the preferred therapy for the great majority of patients. The "preferred" therapy is the drug which produces normal ambulatory blood pressure, with the greatest reduction in blood pressure without unacceptable side effects. We will recruit 50 patients from the Houston Pediatric and Adolescent Hypertension Program clinic. For each patient, the three drugs will be prescribed in random order and each drug will be taken for 2 weeks. The effectiveness of each therapy will be measured with 24-h ambulatory blood pressure monitoring, and tolerability will be assessed using a side effect questionnaire. Participants will rotate through treatment periods, repeating drugs and adjusting doses until the preferred therapy is identified. In assessing whether one of the medications is most effective for the majority of subjects, the primary outcome will be the percentage of participants for whom each drug is selected as the preferred therapy. We hypothesize that no drug will be selected for the great majority of the subjects, a finding that would support consideration of clinical use of n-of-1 trials. Secondary analyses will explore whether patient characteristics predict which medication will be selected as a preferred drug., Discussion: This study will help optimize care of participating patients and provide evidence regarding the usefulness of n-of-1 trials in identifying appropriate treatment for children with hypertension and potentially other disorders., Trial Registration: Clinicaltrials.gov NCT02412761 (registered 4/8/2015).

Background: IgA nephropathy (IgAN) is the most common glomerulonephritis world-wide and a cause of end-stage kidney disease (ESKD) in 15% to 20% of patients within 10 years and in 30% to 40% of patients within 20 years from the onset of disease. This is an update of a review first published in 2003., Objectives: To determine the benefits and harms of immunosuppression for the treatment of IgAN., Search Methods: For this review update we searched the Specialised Register to 19 February 2015 through contact with the Trials Search Co-ordinator using search terms relevant to this review., Selection Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs of treatment for IgAN in adults and children and that compared immunosuppressive agents with placebo, no treatment, or other immunosuppressive or non-immunosuppressive agents., Data Collection and Analysis: Two authors independently assessed study risk of bias and extracted data for population characteristics, interventions and outcomes including mortality, infection, hospitalisation, ESKD requiring renal replacement therapy (dialysis or kidney transplantation), doubling of serum creatinine, remission of proteinuria, and end of treatment urinary protein excretion, serum creatinine, and glomerular filtration rate.Estimates of treatment effect and hazards were summarised using random effects meta-analysis. Treatment effects were expressed as relative risk (RR) and 95% confidence intervals (95% CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes., Main Results: We included 32 studies comprising 1781 participants. Risk of bias within the included studies was generally high: 22 studies (69%) did not describe the method used to generate the randomisation sequence; 24 (75%) did not describe the methods used to conceal allocation; performance bias was not reported or high in 30 studies (94%); detection bias was unclear in 31 studies (97%); attrition bias was low in 14 studies (44%), unclear in eight (25%) and high in 12 studies (38%); reporting bias was low in 21 studies (67%) and high in 10 studies (31%); and four studies received industry funding or were terminated early (13%).Steroids lowered risks of progression to ESKD (6 studies, 341 participants: RR 0.44, 95% CI 0.25 to 0.80), and doubling of serum creatinine (6 studies, 341 participants: RR 0.45, 95% CI 0.29 to 0.69), lowered urinary protein excretion (6 studies, 263 participants: MD -0.49 g/24 h, 95% CI -0.72 to -0.25); and preserved glomerular filtration rate (4 studies, 138 participants: MD 17.87 mL/min/1.73 m(2), 95% CI 4.93 to 30.82) compared to no treatment or placebo. Combining steroids plus renin-angiotensin-system (RAS) inhibitors lowered the risk of progression to ESKD (2 studies, 160 participants: RR 0.16, 95% CI 0.04 to 0.59) and reduced urinary protein excretion (1 study, 38 participants: MD -0.20 g/24 h, 95% CI -0.26 to -0.14) compared with RAS inhibitors or steroids alone. Cytotoxic agents (azathioprine) plus steroid regimens plus dipyridamole increased remission of proteinuria (1 study, 78 participants: RR 1.24, 95% CI 1.01 to 1.52) compared to steroids alone but had uncertain effects on other outcomes.Mycophenolate mofetil plus RAS inhibitors lowered the risk of progression to ESKD (1 study, 40 participants: RR 0.22, 95% CI 0.05 to 0.90), improved remission of proteinuria (1 study, 40 participants: RR 2.67, 95% CI 1.32 to 5.39) and reduced urinary protein excretion (1 study, 40 participants: MD -1.26 g/24 h, 95% CI -1.46 to -1.06). Effects of other immunosuppressive regimens (including cyclosporin, leflunomide) were inconclusive primarily due to insufficient data from the individual studies. Subgroup analyses to determine the impact of patient characteristics on treatment effectiveness were not possible., Authors' Conclusions: The optimal management of IgAN remains uncertain although corticosteroid therapy may lower the risks of kidney disease progression and need for dialysis or transplantation. Evidence for treatment effects of immunosuppressive agents on mortality, infection, and cancer is generally sparse or low-quality and insufficient to guide clinical practice. Available RCTs are few, small, have high risk of bias - particularly selective reporting - and generally do not systematically identify treatment-related harms. Subgroup analyses to identify specific patient characteristics that might predict better response to therapy were not possible. Larger placebo-controlled studies of corticosteroid therapy or mycophenolate mofetil which are sufficiently powered to evaluate patient-relevant end points including adverse events and that examine the optimal duration of treatment are now required in populations with IgAN with a range of kidney function.

Renal vein thrombosis (RVT) is an uncommon condition in adults and may be caused by endothelial damage, stasis, or hypercoagulable states. RVT is commonly identified in patients with nephrotic syndrome or malignancy. We present the case of a 57-yearold man with no past medical history who presented with a 1-month history of abdominal pain, dysuria, and hematuria. Initial laboratory studies were consistent with acute kidney injury (AKI). Imaging revealed bladder distension, enlargement of the prostate, bilateral hydronephrosis, and left renal vein thrombosis extending into the inferior vena cava. His renal failure and presenting symptoms resolved with placement of a Foley catheter and ureteral stent. The patient was discharged on anticoagulation. Here, we report a rare case of RVT that appears to have occurred as a consequence of obstructive uropathy causing massive bladder distention resulting in compression of the renal vein.

Nephrologists rely on valid clinical studies to inform their health care decisions. Knowledge of simple statistical principles equips the prudent nephrologist with the skills that allow him or her to critically evaluate clinical studies and to determine the validity of the results. Important in this process is knowing when certain statistical tests are used appropriately and if their application in interpreting research data will most likely lead to the most robust or valid conclusions. The research team bears the responsibility for determining the statistical analysis during the design phase of the study and subsequently for carrying out the appropriate analysis. This will ensure that bias is minimized and "valid" results are reported. We have summarized the important caveats and components in correctly choosing a statistical test with a series of tables. With this format, we wish to provide a tool for the nephrologist/researcher that he or she can use when required to decide if an appropriate statistical analysis plan was implemented for any particular study. We have included in these tables the types of statistical tests that might be used best for analysis of different types of comparisons on small and on larger patient samples., (© 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The randomized controlled trial (RCT) remains the "gold standard" for the evaluation of therapies. Despite some progress during the past decade, the number and quality of published RCTs addressing the core issues for patients with CKD and with renal diseases, in general, lag behind other areas in internal medicine. The paucity of robust evidence results in fewer patients receiving evidence-based therapies in nephrology and fewer rigorous systematic reviews to inform nephrology practice and health care policy. Because trials of lower methodologic rigor continue to be published, the evidence-based practitioner must evaluate new evidence from the medical literature carefully before incorporating that evidence into their clinical practice. The types of errors that may limit the validity or applicability of evidence from RCTs is outlined. A detailed discussion of the most important design elements for the conduct of a high-quality RCT is described in the text. These considerations are placed into the context of critical appraisal tools. These tools allow the clinician to efficiently assess the quality of published RCTs and to determine how the new RCT evidence should change current best practice., (© 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Although Henoch-Schönlein purpura (HSP) is the most common form of renal vasculitis in childhood, progression to ESRD is rare, and there are few data on outcomes of renal transplantation in patients with HSP., Design, Setting, Participants, & Measurements: This is a matched retrospective cohort study of renal allografts using the United Network of Organ Sharing database (1987 to 2005). Of the 189,211 primary renal allografts, there were 339 with a diagnosis of HSP. The primary end point was allograft survival., Results: Compared with the remainder of the database, the HSP population was younger (25 years versus 46 years), and had a higher proportion of women (47% versus 40%), live donors (50% versus 35%), and Caucasians (77% versus 60%). Controlling for age, gender, donor source, ethnicity, and year of transplantation, death-censored graft survival for patients with HSP was 80.0% at 5 years and 58.8% at 10 years compared with 79.0% at 5 years and 55.4% at 10 years in the non-HSP population. Among patients with reported causes of graft loss, failure from recurrent disease occurred in 13.6% of patients with HSP, compared with 6.6% in the non-HSP population. When analyzing allograft survival in recipients with HSP compared with those with IgA nephropathy, there was no difference in 10-year allograft survival (58.4% and 59.3%, respectively)., Conclusions: These data indicate that although there is an increased risk of graft failure attributable to recurrent disease in patients with HSP, a diagnosis of HSP has little effect on overall renal allograft survival.

Background: IgA nephropathy (IgAN) is the most common primary glomerular disease with approximately 30% to 40% of patients progressing to end-stage kidney disease (ESKD) within 20 years. The most common regimens include immunosuppressive agents, however the risks of long-term treatment often outweigh the potential benefits. Non-immunosuppressive options, including fish oils, anticoagulants, antihypertensive agents and tonsillectomy have also been examined but not reviewed systematically., Objectives: To assess the benefits and harms of non-immunosuppressive treatments for treating IgAN in adults and children., Search Strategy: In July 2010 we searched the Cochrane Renal Group's specialised register, CENTRAL (in The Cochrane Library), MEDLINE (from 1966) and EMBASE (from 1980). We also searched reference lists of included studies, review articles and contacted local and international experts., Selection Criteria: Randomised controlled trials (RCTs) of non-immunosuppressive agents in adults and children with biopsy-proven IgAN were included., Data Collection and Analysis: Two authors independently reviewed search results, extracted data and assessed study quality. Results were expressed as mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI) using a random-effects model., Main Results: We included 56 studies (2838 participants). Antihypertensive agents were the most beneficial non-immunosuppressive intervention for IgAN. The antihypertensives examined were predominantly angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) or combinations of both, versus other antihypertensives and other agents. The benefits of antihypertensive agents, particularly inhibitors of the renin angiotensin system, appear to potentially outweigh the harms in patients with IgAN. The benefits are largely manifest as a reduction in proteinuria, a surrogate outcome. There is no evidence that treatment with any of the antihypertensive agents evaluated affect major renal and/or cardiovascular endpoints or long-term mortality risk beyond the benefit that arises from controlling hypertension in patients with IgAN. The RCT evidence is insufficiently robust to demonstrate efficacy for any of the other non-immunosuppressive therapies evaluated here., Authors' Conclusions: IgAN remains a disease in search of adequately powered RCTs to reliably inform clinical practice. More and better evidence is needed to understand the magnitude of benefit and the possible risks of anti-hypertensive or more specifically of ACEi/ARB therapy alone or in combination and which specific types of patients with the IgAN might have the greatest potential for benefit. For other non-immunosuppressive therapies, where neither benefit nor significant harm has yet to be demonstrated, there remains some justification for further exploration of the potential benefits.

The changes in phosphate (PO(4)) metabolism across the spectrum of chronic kidney disease (CKD) and specific strategies to address these abnormalities by reducing PO(4) loads are discussed in this review. This review also addresses briefly the evidence for specific PO(4) serum targets in CKD and endstage renal disease (ESRD) and the potential for other biomarkers such as fibroblast growth factor-23 (FGF-23) to define disease and monitor the effectiveness of therapy. As renal function declines, single nephron excretion of PO(4) must increase to maintain PO(4) balance. Abnormalities in PO(4) metabolism occur early in CKD. Compensatory changes in renal PO(4) handling are sufficient to maintain a normal serum PO(4) level in early stages of CKD, but in more advanced CKD, these processes no longer suffice and overt hyperphosphatemia develops. The resulting increased PO(4) burden contributes directly to development of secondary hyperparathyroidism. The FGF-23 increases early in CKD, likely in response to abnormal PO(4) metabolism, and mediates processes that help restore serum PO(4) levels to normal in CKD stage 3 and in early stage 4. The increased PO(4) burden and subsequent overt hyperphosphatemia are associated with increased mortality and morbidity. Dietary PO(4) restriction, modification of dialysis prescriptions, and administration of oral PO(4) binders can restore PO(4) balance. As CKD progresses, population-based studies demonstrate that diet alone is typically not able to prevent or treat hyperphosphatemia. Dialysis modalities that are currently used often fail to remove sufficient PO(4) to prevent hyperphosphatemia in patients with an inadequately controlled dietary PO(4) load. This is particularly likely among patients without significant residual renal function. Thus, in the majority of ESRD patients, PO(4) binders remain the mainstay of therapy for hyperphosphatemia. All currently available PO(4) binders can restore serum PO(4) to the required level when administered appropriately and in conjunction with dietary PO(4) restrictions. PO(4) binders differ regarding their potential side-effects and impact on long-term patient-centered outcomes. Which of the PO(4) binders might result in the most favorable survival and cardiovascular morbidity profiles and which remain uncertain, remains a subject of considerable clinical investigation. Compelling observational and more limited randomized controlled trial (RCT) evidence support the view that PO(4) binders might differ in their effects on mortality and/or morbidity. The limited evidence from RCTs is mostly congruent with the findings from large observational studies. In particular, evidences from both epidemiologic and RCT support the view that excess calcium administration may independently increase the risk of cardiovascular disease in individuals with normal renal function and in patients with CKD and ESRD. Additional RCT evidence might help determine the degree at which any increased risk from oral calcium exposure can be mitigated with the use of noncalcium-based PO(4) binders. Judicious control of PO(4) early in CKD, possibly monitored by measures of FGF-23, could potentially reduce the risk of development of renal secondary hyperparathyroidism and all of the adverse clinical consequences of poorly controlled CKD-mineral and bone disorder. The mainstays of therapy are likely to include a balance of dietary restriction and PO(4) binders to reduce PO(4) input, and in ESRD patients, dialysis modalities to augment PO(4) output., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: The overall objective of this study was to estimate the costs and outcomes associated with treatment with sevelamer for hyperphosphataemia compared with calcium-based binders., Methods: Using published data on mortality and hospitalisation rates, a Markov model was developed to predict health outcomes and associated costs for the treatment of hyperphosphataemia using either sevelamer or calcium binders in chronic kidney disease patients who had recently started haemodialysis. Patient outcomes were modelled for 5 years, and incremental cost-effective ratios (ICERs) were calculated for sevelamer relative to calcium carbonate and calcium acetate binders. The perspective adopted was that of the UK National Health Service., Results: The total 5-year discounted treatment cost for patients treated with sevelamer is pound 24,216, while for the calcium carbonate group total cost was pound 17,695. This is an incremental cost of pound 6521 per sevelamer-treated patient over 5 years. Patients receiving sevelamer can be expected to experience 2.70 quality-adjusted life years (QALYs) compared to 2.46 for those treated with calcium carbonate (i.e. an incremental gain of 0.24 QALYs). This results in an incremental cost per QALY of pound 27,120 and an incremental cost per life year gained of pound 15,508. Results were similar with calcium acetate., Conclusion: Together with the unique morbidity and mortality benefits, this study suggests that treatment with sevelamer confers clinical benefits with a modest investment of additional economic resources.

Purpose: To learn whether preclinical primary care preceptorships resulted in demonstrable clinical performance benefits to medical students., Method: This was a retrospective cohort study of 267 medical students who elected and 310 students who did not elect to take a four-week primary care preceptorship following the first year of training at the University of Texas Medical School at Houston in 2001-2003. Outcome variables were the students' performances on a written examination testing their integration of basic science and fundamentals of clinical medicine and performances on a comprehensive objective structured clinical examination (OSCE). After adjusting for factors that might have explained differences in the students' performances, logistic regression models were used to assess the association of the outcome variables with participation in a preceptorship., Results: Students who participated in any one of the preceptorships performed better on the OSCE and on the fundamentals of clinical medicine examination than students who did not participate (p < .01). Students who participated in the family medicine or pediatric preceptorship scored higher on an OSCE (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.01-2.78 and OR, 2.26; 95% CI, 1.18-4.36, respectively) than those students who did not participate in a preceptorship. Students who participated in the internal medicine preceptorship scored higher on the fundamentals of clinical medicine examination (OR, 3.18; 95% CI, 1.92-5.23)., Conclusions: Preliminary evidence indicates that a short preclinical primary care preceptorship can help medical students to consolidate and integrate the fundamental cognitive and clinical skills they will apply during the clinical years of medical training.

Background: It is unclear whether the protective benefits of regular physical activity on mortality extend to patients with end-stage renal disease (ESRD). We tested this hypothesis in a national cohort of new patients with ESRD in the United States., Methods: Data for a subset of patients (n = 2,507; 62%) from the Dialysis Morbidity and Mortality Wave 2 study were used to explore the associations of exercise and limitations in physical activity with mortality., Results: Overall, 56% of patients exercised less than once a week, whereas the remainder reported more frequent physical activity; 2 to 3 times/wk in 18%, 4 to 5 times/wk in 6%, and daily exercise in 20%. Severe limitations in vigorous and moderate physical activities were reported by 75% and 42%, respectively. Mortality risks were greatest for those with severe limitations in either moderate (relative risk [RR], 1.72; 95% confidence interval [CI], 1.44 to 2.05) or vigorous physical activities (RR, 1.51; 95% CI, 1.20 to 1.90) compared with those reporting minimal or no limitations. Conversely, mortality risks were lower for patients who exercised 2 to 3 (RR, 0.74; 95% CI, 0.58 to 0.95) or 4 to 5 times/wk (RR, 0.70; 95% CI, 0.47 to 1.07), whereas no advantage was associated with daily exercise (RR, 1.06; 95% CI, 0.86 to 1.30)., Conclusion: Although limitations in physical activity are common among new patients with ESRD in the United States and correlate highly with increased mortality risk, this study shows an association of frequent exercise of up to 4 to 5 times/wk with improved survival. The surprising lack of association of daily exercise with increased survival deserves additional study.

Differences in survival have been reported among ethnic groups in the general population. Whether these extend to patients with ESRD is unclear. Using national data, mortality risks of ethnic groups who began dialysis treatment in the United States between May 1, 1995, and July 31, 1997, were compared over 2 yr. Patients were classified as Hispanic or non-Hispanic and then subclassified by race forming six race-specific subgroups: Hispanic white, black, and other and non-Hispanic white, black, and other. Mortality rates for Hispanics compared with non-Hispanics were 19.2 versus 26 per 100 patient-years at risk for those with diabetes and were 14.7 versus 22.7 per 100 patient-years at risk for those without diabetes. For those with diabetes, adjusted mortality risks for Hispanics versus non-Hispanics were 30% lower (95% confidence interval [CI], 26 to 34%). In subgroup analysis, mortality risks for Hispanic whites and Hispanic blacks were 35% (95% CI, 31 to 39%) and 33% (95% CI, 12 to 48%) lower than non-Hispanic whites and were similar in magnitude to those of non-Hispanic blacks (32% lower; 95% CI, 29 to 35%) and non-Hispanic other (33% lower; 95% CI, 28 to 39%). Interestingly, mortality risks for Hispanic others were not significantly different from non-Hispanic whites. For those without diabetes, adjusted mortality risks for Hispanics versus non-Hispanics were 17% lower (95% CI, 9 to 23%), and subgroup analysis yielded similar patterns to those of individuals with diabetes. The survival advantage of Hispanic over non-Hispanic patients who receive chronic dialysis treatment in the United States is not consistent across subgroups and is modified by race. Cultural and genetic differences as well as variation in the access and delivery of care before and while on dialysis may account for these differences.

Metals and minerals that depend on renal clearance may accumulate to toxic levels in patients with marginal kidney function. Toxicities of aluminum-based phosphate binders became apparent approximately 25 years ago. Nephrologists now recognize cardiovascular calcification may follow use of calcium-based phosphate binders. Five lessons can be learned: (1)safety must not be assumed in absence of data; (2) all evidence for causal linkage of toxicities from therapeutics must be considered, including animal data; (3) clinical trials are unlikely to reveal the spectrum of problems from long-term drug exposure; (4) complications can remain unrecognized until late in post-introduction surveillance; (5) minerals important for normal function can be toxic with excess accumulation. Introduction of new agents necessitates caution - it is difficult to change practice once a therapeutic is commonplace. Lessons learned about hazards of past phosphate binders must be applied judiciously when evaluating long-term risks/safety of novel metal-based binders such as lanthanum carbonate.

Immunoglobulin A (IgA) nephropathy is a worldwide disease that causes end-stage kidney disease (ESRD) in up to 15-20% of affected patients within 10 years from the apparent onset of disease and in up to 30-40% of individuals within 20 years from diagnosis. No specific treatment has been established and there is wide variation in current practice. This systematic review evaluates the use of immunosuppressive agents to treat patients with IgA nephropathy. The Cochrane Renal Group Specialized Register, Cochrane Controlled Trial Registry, MEDLINE, EMBASE and article reference lists were searched for randomized or quasi randomized trials. Two independent reviewers assessed studies for inclusion criteria (biopsy proven IgA nephropathy, randomized trial, use of immunosuppressive agents) and extracted data regarding the effects of immunosuppressive agents on ESRD, doubling of serum creatinine, glomerular filtration rate, urinary protein excretion and side-effects. Data were analysed with a random effects model. The published trials were few (13 trials, 623 patients) and were generally of poor quality. Compared with placebo, steroids were associated with a lower risk of progression to ESRD (six trials, 341 patients, RR 0.44, 95% CI 0.25-0.80) and lower end-of-trial proteinuria (six trials, 263 patients, weighted mean difference (WMD) -0.49 g/day, 95% CI -0.25 to -0.72). Treatment with alkylating agents significantly reduced end of treatment proteinuria (two trials, 122 patients, WMD -0.94, 95% CI -0.46 to -1.43). Although the optimal management of patients with IgA nephropathy remains uncertain because of limitations with the existing published data, immunosuppressive agents are a promising strategy and should be investigated further.

Background: It has been hypothesized that peritoneal dialysis compared to hemodialysis may be less effective in large patients with end-stage renal disease (ESRD)., Methods: We tested this hypothesis in a cohort of 134,728 new ESRD patients who were initiated on dialysis from May 1, 1995 to July 31, 1997 using data from United States Renal Data System (USRDS). Cox regression models evaluated the association of body mass index (BMI) in quintiles (8.8-20.9, 20.9-23.5, 23.5-26.1, 26.1-30.0, 30.0-75.2 kg/m(2)) with mortality over 2 years in peritoneal dialysis and hemodialysis patients separately, while time-dependent models evaluated the relative risk (RR) of death by modality for each BMI quintile., Results: For hemodialysis, the adjusted RR of death was greatest for patients with BMI 30.0 (RR = 0.97, 95% CI 0.96-0.99 for diabetic and RR = 0.97, 95% CI 0.95-0.98 for nondiabetic patients) compared with the referent (23.5-26.1; RR = 1.00). For peritoneal dialysis, the RR of death was also higher for patients with a BMI <20.9 (RR = 1.20, 95% CI 1.00-1.43 for diabetic and RR = 1.39, 95% CI 1.19-1.64 for nondiabetic patients) but no survival advantage was associated with higher BMI values. The RR of death (peritoneal dialysis/hemodialysis) for each BMI quintile was 0.99, 1.12, 1.26 (P < 0.01), 1.15 (P < 0.01), and 1.44 (P < 0.0001) for diabetic and were 1.07, 1.01, 0.96, 1.04, and 1.22 (P < 0.01) for nondiabetic patients, respectively., Conclusion: We conclude that body size modifies the impact of dialysis modality on mortality risk among new ESRD patients in the United States. The selection of hemodialysis over peritoneal dialysis was associated with a survival advantage in patients with large body habitus.

Background: It is hypothesized, but not proven, that peritoneal dialysis might be the optimal treatment for end-stage renal disease (ESRD) patients with established congestive heart failure (CHF) through better volume regulation compared with hemodialysis., Methods: National incidence data on 107,922 new ESRD patients from the Center for Medicare and Medicaid Services (CMS) Medical Evidence Form were used to test the hypothesis that peritoneal dialysis was superior to hemodialysis in prolonging survival of patients with CHF. Nonproportional Cox regression models evaluated the relative hazard of death for patients with and without CHF by dialysis modality using primarily the intent-to-treat but also the as-treated approach. Diabetics and nondiabetics were analyzed separately., Results: The overall prevalence of CHF was 33% at ESRD initiation. There were 27,149 deaths (25.2%), 5423 transplants (5%), and 3753 (3.5%) patients lost to follow-up over 2 years. Adjusted mortality risks were significantly higher for patients with CHF treated with peritoneal dialysis than hemodialysis [diabetics, relative risk (RR) = 1.30, 95% confidence interval (CI) 1.20 to 1.41; nondiabetics, RR = 1.24, 95% CI 1.14 to 1.35]. Among patients without CHF, adjusted mortality risk were higher only for diabetic patients treated with peritoneal dialysis compared with hemodialysis (RR = 1.11, 95% CI 1.02 to 1.21) while nondiabetics had similar survival on peritoneal dialysis or hemodialysis (RR = 0.97, 95% CI 0.91 to 1.04)., Conclusion: New ESRD patients with a clinical history of CHF experienced poorer survival when treated with peritoneal dialysis compared with hemodialysis. These data suggest that peritoneal dialysis may not be the optimal choice for new ESRD patients with CHF perhaps through impaired volume regulation and worsening cardiomyopathy.

Background: Early identification of persons at risk for kidney disease provides an opportunity to prevent or delay its progression and decrease morbidity and mortality. Our hypothesis was that implementation of a targeted screening program in communities with high-risk populations would detect previously unidentified persons with or at high risk for chronic kidney disease (CKD) with a prevalence that exceeds that predicted for CKD in the general population., Methods: Persons with hypertension or diabetes or a first-order relative with hypertension, diabetes, or kidney disease were screened for kidney disease risk factors. Blood pressure, blood glucose level, serum creatinine level, hemoglobin level, microalbuminuria, hematuria, pyuria, body mass index, and estimated glomerular filtration rate (EGFR) were evaluated., Results: Six thousand seventy-one eligible persons were screened from August 2000 through December 2001: of these persons, 68% were women, 43% were African American, 36% were white, 10% were Hispanic, and 5% were Native American. Most reported high-school education or more (84%) and health insurance coverage (86%). Twenty-seven percent met the screening definitions for diabetes; 64%, for hypertension; 29%, for microalbuminuria; 8%, for anemia; 18%, for hematuria; 13%, for pyuria; 5%, for elevated serum creatinine level; 16%, for reduced EGFR; and 44%, for obesity. Among participants without a reported history of specified conditions, screening identified 82 participants (2%) with diabetes, 1,014 participants (35%) with hypertension, 277 participants (5%) with elevated serum creatinine levels, 839 participants (14%) with reduced EGFRs, and 1,712 participants (29%) with microalbuminuria. Thirty-five percent of participants with a history of diabetes had elevated serum glucose levels at screening (> or =180 mg/dL [10 mmol/L]), and 64% with a history of hypertension did not have blood pressure controlled to less than 140/90 mm Hg. Only 18% of participants with a history of diabetes and 31% with a reduced EGFR had blood pressure controlled to less than 130/80 mm Hg and less than 135/85 mm Hg, respectively., Conclusion: Targeted screening is effective in identifying persons with previously unidentified or poorly controlled kidney disease risk factors, as well as persons with a moderately decreased EGFR.

Background: IgA nephropathy (IgAN) is a world-wide disease and the cause of end-stage renal failure (ESRF) in 15 to 20% of patients within 10 years and in 30 to 40% of individuals within 20 years from the apparent onset of disease. No specific treatment has yet been established but many approaches have been investigated., Objectives: To assess the benefits and harms of immunosuppressive treatment for IgAN., Search Strategy: We searched The Cochrane Renal Group's specialized register (May 2003), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2002) MEDLINE (1966 - September 2002), EMBASE (1988 - September 2002) and handsearched reference lists of retrieved articles and conference proceedings., Selection Criteria: Randomized controlled trials (RCTs) and quasi-RCTs comparing treatment of IgAN with immunosuppressive agents against placebo, no treatment, other immunosuppressive or non-immunosuppressive agents., Data Collection and Analysis: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes, with 95% confidence intervals (CI)., Main Results: Thirteen eligible RCTs involving 623 patients were identified. All identified RCTs had a placebo, no treatment or warfarin/dipyridamole control group. Seven trials used steroids, three used alkylating agents/cyclosporin and three used combinations of steroids and alkylating agents/cyclosporin. No trial directly compared steroids versus alkylating agents/cyclosporin. Quality was sub-optimal. Steroids were associated with a lower risk of progression to ESRF (RR 0.44, 95% CI 0.25 to 0.80) and lower urinary protein excretion (WMD -0.49 g/24h, 95% CI -0.72 to -0.12). Urinary protein excretion was lower for patients treated with alkylating agents/cyclosporin compared to placebo/no treatment (WMD -0.94 g/24h, 95% CI -1.43 to -0.46). There was no significant reduction of urinary protein excretion with combination treatment of steroids and alkylating agents compared with placebo/no treatment., Reviewer's Conclusions: The optimal management of IgAN remains uncertain. The RCTs identified were small, of sub-optimal methodological quality and tended to only report favorable and surrogate outcomes without a thorough reporting of treatment harms. All outcomes favor the use of immunosuppressive interventions, with steroids appearing to be the most promising. Further study, in the form of RCTs, is necessary to ascertain which patients would benefit from these interventions, whether they are the ones with early signs of renal dysfunction or those with more advanced renal impairment.