By I. Curtis. University of the Southwest.
The intervention is less costly and more clinically effective than all other relevant alternatives order zithromax 100mg fast delivery antibiotics for acne problems. In this case purchase zithromax with visa antibiotic resistance nps, no ICER is calculated as the strategy in question dominates the alternatives cheap 250 mg zithromax with mastercard infection 6 weeks after c section. The intervention has an ICER of < £20,000 per QALY compared with the next best alternative. This means that an investment of up to £20,000 in order to achieve an additional QALY is considered cost-effective. A cost-effectiveness acceptability curve is produced to illustrate the probability of the intervention being cost-effective at different thresholds. If the intervention is less effective and more costly than the comparator, the intervention is considered dominated. In this case, no ICER or cost-effectiveness acceptability curve is produced. Cost–consequence analysis We presented a tabular representation of costs versus changes in primary and secondary outcomes in a cost–consequence analysis. The cost–consequence approach presents all relevant outcome measures alongside the costs (without combining them into an ICER), to leave decision-makers the option to form their own view of relative importance. Health economics: sensitivity analysis Deterministic (univariate) sensitivity analyses investigated the robustness of the results to changes in estimated costs and outcomes. All ICERs were recalculated after changing the value of a range of parameters individually to estimate the robustness of the ICER (Table 14). Probabilistic sensitivity analysis with changes to the values of all chosen parameters [usually within the 95% confidence intervals (CIs) or a reasonable, defined range], used bootstrap resampling to determine the probability that the intervention was cost-effective when all uncertainty associated with the individual parameters was considered. The results of the probabilistic sensitivity analysis were expressed as percentage probability that the intervention was cost-effective. Budget impact analysis The budgetary impact of the adoption of the PRISM scoring tool in primary care was estimated from a NHS perspective based on the differences between the cost of emergency admissions and total cost, as obtained as part of the trial. We calculated the total budget impact per 100,000 patients registered in the TABLE 14 Parameter changes for univariate sensitivity analysis Parameter Change from base case PRISM pre-activation Minimum (all done by PM) and maximum (all done by GP) cost PRISM activation support Minimum (no site visits required) and maximum (all surgeries need site visit to assist with set-up) cost PRISM opportunity time for GP surgeries Minimum and maximum time spent during trial period Number of emergency admissions 95% CI Primary care costs Minimum (all done by nurse) and maximum (all done by GP) cost Secondary care costs Lower and upper quartile costs for all secondary cost components, as reported in NHS Reference Costs 2014/1568 CI, confidence interval. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 31 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. METHODS trial GP surgeries, as observed over the trial period. For transparency, unadjusted and adjusted analyses are presented. Deterministic sensitivity analysis used the lower and upper quartile unit costs – weighted across Healthcare Resource Groups and for activity – to estimate worst- and best-case scenarios of PRISM budget impact. Stakeholder views Focus groups, interviews and questionnaire We collected qualitative data from GPs and practice staff, at baseline and after launching the PRISM intervention, to explore current practice in chronic conditions management and changes initiated by PRISM (see Table 11 for details regarding numbers of focus groups planned). Questions explored attitudes, expectations and experience relating to predictive risk stratification, specifically the PRISM tool, including barriers to and facilitators of use. Before activating PRISM, we conducted four focus groups with staff from participating practices, two in the largest locality within the health board, and one in each of the other two localities. We interviewed GPs who could not take part in a focus group, by telephone or face to face. We also conducted a focus group with senior managers and community-based practitioners. Focus groups were used to explore different views and experiences by encouraging group interaction. We purposively sampled half the participating practices and sampled a PRISM user in each for interviews face to face between 3 and 6 months after PRISM was activated in their practice, and again at the end of the intervention phase, approximately 18 months after activation in the first practices. We asked the other participating practices to complete online questionnaires at the same time points. We used responses from early adopters to inform later interviews. This enabled us to explore variations between participating practices. In addition, at 18 months, we interviewed a senior manager within ABM UHB to explore area-wide issues in patient management and the effects of PRISM in general practices. Two other managers declined because they had moved to other roles. To gain historical, managerial and political insights into the development and scope of PRISM, we also interviewed six managers (health services commissioners and policy-makers) with all-Wales perspectives at baseline, either face to face or by telephone. We also conducted six interviews with seven respondents (one interview had two respondents) from non-participating health boards across Wales to examine their experience of PRISM and their views of its role and potential. Three experienced researchers from the study team (BAE, AP and MRK) conducted all focus groups and interviews, lasting between 30 and 90 minutes. We made field notes after each focus group or interview. Qualitative analysis We recorded and transcribed the focus groups and interviews and analysed them thematically. We chose this approach as it is a systematic and transparent method of analysis that generates themes from the explicit and implicit ideas contained in the original accounts of participants. Four team members (researchers BAE, MRK, AP and service user SW) read the transcripts and developed a coding framework. One researcher then led the analysis with the others independently supporting key stages of coding, 73–75 generating themes and interpretation, thus encouraging a critical stance to test and confirm findings. NPT is a conceptual framework to explain implementation of innovations in health care. How people understand the innovation and its purpose (coherence). What decisions people take about using it, based on perceived advantages (cognitive participation). What people do to bring the innovation into everyday use (collective action). How the innovation is reviewed, modified or abandoned (reflexive monitoring). Sample size and power We derived data on the number of emergency admissions per patient, the primary outcome for this study, from routine data, in principle, for all non-dissenting patients. We expected SAIL to yield data on about 250,000 people. We excluded people not registered with a study practice on day 1, and defined their final date in the study as the earliest of the date of death, the date of registration with another practice (including another study practice) or the end of the study. The Consolidated Standards of Reporting Trials (CONSORT) flow chart (see Figure 3) recorded the numbers dissenting or withdrawing from the study, or otherwise leaving before its end. In considering sample sizes for postal questionnaires measuring secondary outcomes, we identified few general practice studies with ICCs of > 0.
The decrease in PTH and hypercalcem ia decrease the activity of the C-cells 1- -hydroxylase enzym e located in the Kidney – ↑CT proxim al tubular (PT) cells of the nephron buy 100 mg zithromax with mastercard antibiotic 7146, which in turn discount 100mg zithromax bacteria vaginosis icd 9, decreases the synthesis of – – + 1 generic zithromax 250mg fast delivery treatment for dogs bitten by ticks,25-dihydroxy-vitam in D3 (1,25(O H )2D3). H ypercalcem ia stim ulates the C cells in the PTH↑ PTH Gastrointestinal thyroid gland to increase synthesis of calci- tract – – tonin (CT). Bone resorption by osteoclasts Parathyroid cell PT DCT Nucleus is blocked by the increased CT and decreased PTH. Decreased levels of PTH and 1,25(O H )2D3 inhibit Ca reabsorption in the distal convoluted tubules (DCT) of – the nephrons and overwhelm the effects of – CT, which augm ent Ca reabsorption in the m edullary thick ascending lim b leading to an increase in renal Ca excretion. The – Bone decrease in 1,25(O H ) D decreases gas- – 2 3 trointestinal (GI) tract absorption of dietary 1,25(OH)2D3↓ Ca. All of these effects tend to return serum Ca to norm al levels. Excess parathyroid hormone (PTH) production Increased intestinal absorption of calcium Primary hyperparathyroidism Vitamin D intoxication “Tertiary” hyperparathyroidism* Milk-alkali syndrome* Excess 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) Decreased renal excretion of calcium Vitamin D intoxication Familial hypocalciuric hypercalcemia Sarcoidosis and granulomatous diseases Thiazides Severe hypophosphatemia Impaired bone formation and incorporation of Neoplastic production of 1,25(OH)2D3 (lymphoma) calcium Increased bone resorption Aluminum intoxication* Metastatic (osteolytic) tumors (eg, breast, colon, prostate) Adynamic (“low-turnover”) bone disease* Humoral hypercalcemia Corticosteroids PTH-related protein (eg, squamous cell lung, renal cell cancer) Osteoclastic activating factor (myeloma) 1,25 (OH)2D3 (lymphoma) Prostaglandins Hyperthyroidism Immobilization Paget disease Vitamin A intoxication *Occurs in renal failure. Agent Mechanism of action Saline and loop diuretics Increase renal excretion of calcium Corticosteroids Block 1,25-dihydroxy-vitamin D3 synthesis and bone resorption Ketoconazole Blocks P450 system, decreases 1, 25-dihydroxy-vitamin D3 Oral or intravenous phosphate Complexes calcium Calcitonin Inhibits bone resorption Mithramycin Inhibits bone resorption Bisphosphonates Inhibit bone resorption *Always identify and treat the primary cause of hypercalcemia. Secondary Hyperparathyroidism FIGURE 5-22 Renal failure Pathogenesis of secondary hyperparathyroidism (H PT) in chronic renal failure (CRF). Decreased num bers of proxim al tubular (PT) cells, owing to loss of renal m ass, cause a quantitative decrease in ↓Number of nephrons synthesis of 1,25-dihydroxy-vitam in D (1,25(O H ) D ). Loss of 3 2 3 renal m ass also im pairs renal phosphate (P) and acid (H +) excretion. H ypocalcem ia and hyperphosphatem ia stim ulate PTH release and ↓H+ excretion synthesis and can recruit inactive parathyroid cells into activity and ↓P excretion PTH production. H ypocalcem ia also m ay decrease intracellular degradation of PTH. The lack of 1,25(O H )2D3, which would ordi- 1,25(OH)2D3↓ Hyperphosphatemia narily feed back to inhibit the transcription of prepro-PTH and exert an antiproliferative effect on parathyroid cells, allows the ↓Ca absorption Gastrointestinal increased PTH production to continue. In CRF there m ay be tract decreased expression of the Ca-sensing receptor (CaSR) in parathy- roid cells, m aking them less sensitive to levels of plasm a Ca. Patients with the b allele or the bb genotype vitam in D receptor (VDR) m ay be m ore susceptible to H PT, because the VDR- 1,25(O H )2D3 com plex is less effective at suppressing PTH produc- tion and cell proliferation. The deficiency of 1,25(O H )2D3 m ay also decrease VDR synthesis, m aking parathyroid cells less sensitive to Hypocalcemia ↓Activity 1,25(O H )2D3. Although the PTH receptor in bone cells is downreg- ↓Activity ulated in CRF (ie, for any level of PTH , bone cell activity is lower in CRF patients than in norm al persons), the increased plasm a levels of PTH m ay have harm ful effects on other system s (eg, cardiovascu- VDR CaSR lar system , nervous system , and integum ent) by way of alterations of intracellular Ca. Current therapeutic m ethods used to decrease Increased PTH release in CRF include correction of hyperphosphatem ia, transcription ↓Degradation m aintenance of norm al to high-norm al levels of plasm a Ca, adm in- of PTH istration of 1,25(O H )2D3 orally or intravenously, and adm inistra- Release tion of a Ca-ion sensing receptor (CaSR) agonist [14–16,19–22]. CALCIUM PREPARATIONS Calcium (Ca) salt Tablet size, mg Elemental Ca, mg, % Carbonate 1250 500 (40) Acetate 667 169 (25) Citrate 950 200 (21) Lactate 325 42 (13) Gluconate 500 4. VITAM IN D PREPARATIONS AVAILABLE IN THE UNITED STATES Ergocalciferol Calcifediol Calcitriol (Vitamin D2) (25-hydroxy-vitamin D3) Dihydrotachysterol (1,25-dihydroxy-vitamin D3) Commercial name Calciferol Calderol® (Organon, Inc, DHT Intensol® (Roxane Rocaltrol® (Roche Laboratories, W est Orange, NJ) Laboratories, Columbus, OH) Nutley, NJ) Calcijex® (Abbott Laboratories, Abbott Park, NJ) Oral preparations 50,000 IU tablets 20- and 50-µg capsules 0. Philbrick W M , W ysolm erski JJ, Galbraith S, et al. Louis: of parathyroid horm one-related protein in norm al physiology. Johnson JA, Kum ar R: Renal and intestinal calcium transport: roles of 14. Goodm an W G, Belin TR, Salusky IB: In vivo> assessm ents of vitam in D and vitam in D-dependent calcium binding proteins. Sem in calcium -regulated parathyroid horm one release in secondary N ephrol 1994, 14:119–128. H ebert SC, Brown EM , H arris H W : Role of the Ca2+-sensing receptor 50:1834–1844. Chattopadhyay N , M ithal A, Brown EM : The calcium -sensing 4. Hebert SC, Brown EM : The scent of an ion: calcium-sensing and its roles receptor: a window into the physiology and pathophysiology of in health and disease. Berridge M J: Elem entary and global aspects of calcium signalling. N em eth EF, Steffey M E, Fox J: The parathyroid calcium receptor: a novel therapeutic target for treating hyperparathyroidism. Friedm an PA, Gesek FA: Cellular calcium transport in renal epithelia: N ephrol 1996, 10:275–279. W asserman RH, Fullmer CS: Vitamin D and intestinal calcium transport: 7. Root AW : Recent advances in the genetics of disorders of calcium facts, speculations and hypotheses. Johnson JA, Kum ar R: Vitam in D and renal calcium transport. H olick M F: Defects in the synthesis and m etabolism of vitam in D. Kum ar R: Calcium transport in epithelial cells of the intestine and Practice of N ephrology. W hite CP, M orrison N A, Gardiner EM , Eism an JA: Vitam in D recep- 20. Felsenfeld AJ: Considerations for the treatm ent of secondary hyper- tor alleles and bone physiology. The hyperparathyroidism of chronic renal failure: a receptor gene polym orphism and relative hypoparathyroidism in disorder of growth. Salusky IB, Goodm an W G: Parathyroid gland function in secondary hyperparathyroidism. M ontvale N J: M edical Econom ics Sem Surg O ncol 1997, 13:125–133. Madias aintenance of acid-base homeostasis is a vital function of the living organism. Deviations of systemic acidity in either M direction can impose adverse consequences and when severe can threaten life itself. Acid-base disorders frequently are encountered in the outpatient and especially in the inpatient setting. Effective man- agement of acid-base disturbances, commonly a challenging task, rests with accurate diagnosis, sound understanding of the underlying pathophysiology and impact on organ function, and familiarity with treatment and attendant complications. Clinical acid-base disorders are conventionally defined from the vantage point of their impact on the carbonic acid-bicarbonate buffer system. This approach is justified by the abundance of this buffer pair in body fluids; its physiologic preeminence; and the validity of the iso- hydric principle in the living organism, which specifies that all the other buffer systems are in equilibrium with the carbonic acid-bicar- bonate buffer pair.
Applications for commercial reproduction should be addressed to: NIHR Journals Library buy zithromax 250 mg overnight delivery antibiotic resistant uti in pregnancy, National Institute for Health Research zithromax 100mg lowest price 0g infection, Evaluation purchase zithromax on line amex virus buster, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. REVIEW METHODS We excluded self-care undertaken without any input, guidance or facilitation by services. Although self-care can be, and often is, undertaken without service support, it is rarely the subject of intervention studies. We excluded studies where the effects of self-care support could not be distinguished from broader interventions for LTCs. We excluded studies evaluating service development or quality improvement initiatives in which self-care support was not the predominant component of the intervention. Comparators We included studies in which a self-care support intervention was additional to usual care and compared against usual care alone, or in which a self-care support intervention was compared against a more intensive usual care intervention (e. We excluded studies in which two versions of self-care support were compared and the two interventions were of comparable intensity and content, because such comparisons did not allow for an assessment of the impact of self-care support per se. We restricted our analysis to studies of self-care support that reported quantitative data on patient outcomes and health-care utilisation, as these were the only studies that could answer our brief. Eligible patient outcomes included standardised measures of health-related or generic QoL or disease- specific symptom measures or events. We excluded intermediate outcomes and measures of psychological or clinical variables that did not provide an assessment of subjective health status or QoL [e. In adult populations, such variables are known to be unreliable indicators of health-related quality of life (HRQoL). Eligible outcomes for health-care utilisation comprised data on hospital visits and admissions, emergency care, primary care visits, other scheduled or unscheduled health-care use, patient costs and total costs. Our primary foci were comprehensive measures of health service costs (i. Other, more minor, costs (such as medication use) were identified but not formally analysed. The rationale for this is discussed further in Data preparation and analysis. Design We included randomised controlled trials (RCTs), non-randomised controlled trials (nRCTs), controlled before-and-after studies (CBAs) and interrupted time series designs, as defined according to the Effective Practice and Organisation of Care (EPOC) criteria63 (Box 4). Translation of non-English-language studies was undertaken. Search methods In accordance with the review protocol, our search strategies included electronic database searches, reference list searches, targeted author searches and forward citation searching. Electronic databases We began the process of identifying eligible studies by checking published reviews, including those 26 31 32, , previously undertaken by the research team. We complemented our searches of existing reviews with a primary search of multiple electronic databases, conducted in March 2015. We updated and expanded our existing search strategies to ensure that they were sensitive to a broad range of health-care utilisation beyond formal cost-effectiveness analyses. Search terms relating to the key 8 NIHR Journals Library www. Randomisation ensures that participants in each comparison group should differ only in their exposure to the intervention. Randomisation can occur at an individual or cluster (site/region) level. Non-randomised controlled trials Investigators allocate participants to the different groups that are being compared using a method that is not random. Controlled before-and-after studies Decisions about allocation to the different comparison groups are not made by the investigators. Outcomes of interest are measured in both the intervention and control groups before the intervention is introduced and again after the intervention has been introduced. Interrupted time series design Provides a method of measuring the effect of an intervention when randomisation or identification of a control group are impractical. Multiple data points are collected before and after the intervention and the intervention effect is measured against the pre-intervention trend. A search strategy was developed in MEDLINE, using an iterative approach tested against a set of 15 studies known to be relevant to our review. This MEDLINE search strategy was adapted to run on all other databases designated in our protocol. Electronic searches were undertaken on the following health and allied health databases: l MEDLINE (accessed 18 March 2015 via OvidSP; www. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that 9 suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. REVIEW METHODS All databases were searched from inception. Full details of the search strategies, search terms and the specific dates of individual searches are reported in Appendix 1. Additional search strategies included scanning the bibliographies of all relevant retrieved articles, targeted author searches (for additional publications and/or unpublished data identified in conference abstracts) and forward citation searching. No studies were identified that had not been retrieved by other means. Changes to the search protocol All searches were conducted as specified in the original review protocol with the exception of the Health Economic Evaluations Database (HEED). HEED ceased publication prior to study commencement and was not searched as part of the final review. Coverage of the relevant economic evidence base was ensured through searches of the NHS EED, the Health Technology Assessment database, the PEDE and the IDEAS database of economic and finance research. The potential impact of this protocol change was judged to be minimal. Study screening and selection With the exception of the IDEAS database, all records retrieved from the electronic searches were imported into a bibliographic referencing software program (EndNote X5; Thomson Reuters, CA, USA) and duplicate references identified and removed. Review screening and eligibility judgements were managed in Covidence systematic review software (Veritas Health Innovation, Melbourne, VIC, Australia). Pairs of reviewers independently screened all titles and abstracts for eligibility using prespecified inclusion criteria described below. Additional economic abstracts located through IDEAS were managed as hard-copy records and independently screened for eligibility by two reviewers using identical eligibility criteria. To be eligible for full-text screening, search records (titles and abstracts) had to fulfil three initial inclusion criteria: 1. Where both reviewers agreed that the studies did not meet these criteria, studies were excluded from the review. When both reviewers agreed on inclusion, or when there was conflict, full-text articles were retrieved for review.
Pyridoxine is a cofactor for alanine– Thiazide diuretics glyoxylate aminotransferase and can increase the activity of the enzyme in som e patients cheap zithromax 100mg otc antibiotics for kidney infection. Pyridoxine has no role in com bined hepatorenal transplantation best 500 mg zithromax antibiotics for acne philippines. For m ost patients the ideal option is probably a com bined transplantation when their glom erular filtration rate decreases below 25 m L/m in [8 order zithromax 500mg with amex infection z movie,9]. H owever, increasing num bers of patients these grafts within 2 years of transplantation [20,21]. Patient survival with m yelom a and AL am yloid, or prim ary am yloidosis, are now is reduced, owing to infections and vascular complications, to 68% at receiving peripheral blood stem cell transplantations or bone m ar- 1 year and 51% at 2 years. Recurrence is characterized by proteinuria row allografts. Thus, these patients are surviving long enough to 11 m onths to 3 years after transplantation. Recurrent light chain consider renal transplantation. O ver 60 patients with renal failure deposition disease is found in half of patients receiving allografts, with resulting from system ic am yloid A (AA) am yloidosis have been graft loss in one third despite plasmapheresis and chemotherapy. Graft survival in these H eavy proteinuria is seen at the onset of recurrence. AL— prim ary patients is the sam e as that of a m atched population. FIGURE 17-16 M icroradioangiography com paring the vasculature of the kidney in a patient with no disease (panel A) and a patient with hom ozygous sickle cell disease (panel B). Despite the frequency of renal dam age in sickle cell disease, only 4% of patients progress to end-stage renal disease, and little experience exists with renal transplantation. Three patients have been reported with recurrent sickle cell nephropathy. In one case, a patient developed renal dysfunction 3. A second study reported recurrent sickle cell nephropathy leading to graft failure in two of eight patients receiving transplantation. Concentration defects were observed within 12 months of grafting. Patients also suffered an increased incidence of sickle cell crises after renal transplantation, possibly associated with the increase in A B hem atocrit. SLE accounts for approxim ately 1% after transplantation, with overall renal and extrarenal recurrence rates of up to 29% and of all patients receiving allografts, and less renal recurrences alone of up to 16%. Graft loss has been reported in up to 40% of than 1% of these will develop recurrent patients with renal recurrence. In the m ost recent data from the H am m ersm ith H ospital, renal disease. Tim e to recurrence has been however, renal recurrences were rare, with only 0. These patients have often been on long courses of im m unosuppres- tion [24,25]. Cyclosporine therapy does not sive therapy before receiving a graft. It is reasonable to can involve the ureter, causing stenosis and obstructive nephropathy. Serial m onitoring of ensure that serologic test results for SLE are antineutrophil cytoplasm ic antibodies after transplantation is im portant in all patients m inim ally abnorm al before transplantation with vasculitis because changes in titer m ay predict disease relapse [28,29]. Patients with lupus anticoagulant and anticardiolipin antibodies are at risk of throm boem bolic events, including renal graft vein or artery throm bosis. These patients m ay require anticoagulation therapy, or platelet inhibi- tion with aspirin. FIGURE 17-19 RENAL COM PLICATIONS OF HEPATITIS C VIRUS Recurrence of both m esangiocapillary glom erulonephritis (M CGN ) AFTER KIDNEY TRANSPLANTATION and, less frequently, m em branous nephropathy is well described after transplantation. N ineteen cases of de novo or recurrent M CGN after transplantation have been described in patients with Clinical: hepatitis C virus (HCV). Almost all had nephrosis and exhibited Proteinuria sym ptom s 2 to 120 m onths after transplantation. Eight patients had dem onstrable cryoglobulin, nine had hypocom plem entem ia, Nephrotic syndrome and m ost had norm al liver function test results. M em branous GN Microscopic hematuria is the m ost com m on de novo GN reported in allografts, and it is Histologic and laboratory findings possible that HCV infection may be associated with its development Mesangiocapillary glomerulonephritis with or without cryoglobulinemia,. Twenty patients with recurrent or de novo m em branous GN hypocomplementemia, rheumatoid factors and H CV virem ia have been reported. In one study, 8% of patients Membranous nephropathy: normal complement, no cryoglobulinemia or rheumatoid factor with m em branous GN had H CV antibodies and RN A com pared Acute and chronic transplantation glomerulopathy with less than 1% of patients with other form s of GN (excluding M CGN ). Prognosis in these patients was poor, with persistent heavy proteinuria and declining renal function. The overall recurrence rate is approximately 20% to 30% [1,4,31]. These numbers, however, may be an underestimate because of biopsy sampling errors. Patients Risk factor Recurrence rate, % at high risk for recurrence can be identified, particularly children with rapid evolution of their original disease and mesangial expansion Age <5 y 50 on biopsy [1,32]. Recurrence m anifests with proteinuria (often Age < 15 y with progression to end-stage renal disease 80–100 10–40 g/d), developing hours to weeks after transplantation. In within 3 y children the m ean tim e to recurrence is 14 days. Recurrence is not First graft lost from focal segmental glomerulosclerosis 75–85 benign and leads to graft loss in up to half of patients. Patients at Adults without risk factors 10–15 highest risk for recurrence should not receive grafts from living related donors. Graft loss occurs in half of all patients with recurrent focal segmental glomerulosclerosis and nephrotic syndrome. RECURRENT FOCAL SEGMENTAL GLOMERULOSCLEROSIS Patients with recurrent focal segm ental AND ACUTE RENAL FAILURE AFTER TRANSPLANTATION glom erulosclerosis are at substantially increased risk of developing both acute renal failure (panel A) after transplantation Patients with recurrence, n Patients with no recurrence, n and acute rejection episodes (panel B). In one study, 23 of 26 patients with recurrence Acute renal failure (23) 16 7 developed one or m ore episodes of rejec- No acute renal failure (50) 10 40 tion, com pared with only 11 of 40 patients without recurrence. Although the mecha- nism for the increased rate of acute dysfunc- tion and rejection is unclear, proteinuria and dyslipidemia m ay alter the expression of cell B. ACUTE REJECTION EPISODES AM ONG ACUTE RENAL FAILURE CASES surface im m unoregulatory m olecules and m ajor histocom patibility com plex antigens.