Abstract:In recent times the use of larger doses of vancomycin aimed at curbing the increasing incidence of resistant strains of Staphylococcus aureus has led to a wider report of acute kidney injury (AKI). Apart from biological plausibility, causality is implied by the predictive association of AKI with larger doses, longer duration, and graded plasma concentrations of vancomycin. AKI is more likely to occur with the concurrent use of nephrotoxic agents, and in critically ill patients who are susceptible to poor renal perfusion. Although most vancomycin-induced AKI cases are mild and therefore reversible, their occurrence may be associated with greater incidence of end-stage kidney disease and higher mortality rate. The strategy for its prevention includes adequate renal perfusion and therapeutic drug monitoring in high-risk individuals. In the near future, there is feasibility of renoprotective use of antioxidative substances in the delivery of vancomycin.

Routine administration of erythropoietin (EPO)-stimulating agents (ESAs) for the control of anemia has improved the quality of life of subjects with chronic kidney disease (CKD). However, a wide variation in individual response to ESA is often observed. The reasons for EPO resistance include demographic variables such as age and gender distribution, morbidity pattern, and modality of dialysis. Despite suggestions by observational data, there is no biological characteristic that puts children at a disadvantage for adequate response to ESA. On the contrary, children possess a superior capacity for red cell production, including extramedullary erythropoiesis. The reasons for larger requirement of ESA in children (than in adults) are greater inflammatory burden, disproportionate blood loss, and greater EPO dosing by pediatric physicians. To minimize the harmful (including fatal) consequences of EPO resistance, surveillance programs must replenish nutrient (for example, iron and folate) stores, minimize oxidative hemolysis, control hyperparathyroidism, avoid catheter infection, and optimize uremic clearance. This clinical approach is justified by the inadequacy of laboratory diagnosis of pertinent etiological factors. Indeed, the best proof for functional nutrient deficiency is often a therapeutic trial. Finally, there are upcoming therapeutic agents that exploit the capacity for an endogenous EPO synthesis in CKD subjects, and may therefore minimize the off-target effect of excess dosages.

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Among other factors, sophistication of immunosuppressive (IS) regimen accounts for the remarkable success attained in the short- and medium-term solid organ transplant (SOT) survival. The use of steroids, mycophenolate mofetil and calcineurin inhibitors (CNI) have led to annual renal graft survival rates exceeding 90% in the last six decades. On the other hand, attrition rates of the allograft beyond the first year have remained unchanged. In addition, there is a persistent high cardiovascular (CV) mortality rate among transplant recipients with functioning grafts. These shortcomings are in part due to the metabolic effects of steroids, CNI and sirolimus (SRL), all of which are implicated in hypertension, new onset diabetes after transplant (NODAT), and dyslipidemia. In a bid to reduce the required amount of harmful maintenance agents, T-cell-depleting antibodies are increasingly used for induction therapy. The downsides to their use are greater incidence of opportunistic viral infections and malignancy. On the other hand, inadequate immunosuppression causes recurrent rejection episodes and therefore early-onset chronic allograft dysfunction. In addition to the adverse metabolic effects of the steroid rescue needed in these settings, the generated proinflammatory milieu may promote accelerated atherosclerotic disorders, thus setting up a vicious cycle. The recent availability of newer agent, belatacept holds a promise in reducing the incidence of metabolic disorders and hopefully its long-term CV consequences. Although therapeutic drug monitoring as applied to CNI may be helpful, pharmacodynamic tools are needed to promote a customized selection of IS agents that offer the most benefit to an individual without jeopardizing the allograft survival.

FSGS recurs in approximately 30% of transplanted kidneys and may lead to graft loss. We retrospectively examined the efficacy of early and intensive PP without additional IS in pediatric kidney transplant patients with recurrent FSGS at our center. Seven of 24 patients (29%) had nephrotic proteinuria and histologic evidence of FSGS recurrence within 1-5 days post-transplantation. PP was initiated early after transplantation and initially performed daily until sustained decline in proteinuria. PP frequency was then individually tapered according to proteinuria. Recurrent FSGS in all seven patients responded to a four- to 32-wk course of PP. Two of seven patients had a second recurrence of FSGS, and both recurrences remitted after an additional 3-6 wk of PP. Median observation period was 4.5 yr (0.8-16.3 yr). Complete remission of recurrent FSGS has been sustained in all seven patients, and all patients have stable graft function with recent plasma creatinine <1.5 mg/dL in six of seven patients. Most recent urine protein/creatinine is 0.13-0.61 mg/mg in six of seven patients. One patient has heavy proteinuria secondary to chronic allograft nephropathy 16 yr post-transplant. Intensive and prolonged PP, when initiated early in the post-operative period, is effective in treating recurrent FSGS and preventing graft loss without the use of additional immunosuppressants.

Schistosomiasis is the second most common socioeconomically devastating parasitic disease after malaria, affecting about 240 million residents of developing countries. In Africa, it predominantly manifests as urogenital disease, and the main infective agent is Schistosoma hematobium.

Previous studies often report lower responses to erythropoietin (EPO) therapy in pediatric patients on chronic dialysis than those of adults. Because of the greater capacity for hematopoiesis in the younger population, these studies may be confounded by poorly identified variables. Thus, we made parallel studies of pediatric and adult cohorts to explore the relationship between age, gender and other risk factors with EPO resistance. Thirty pediatric subjects (aged 8-20 years) and 66 adult subjects (aged 22-85 years) on chronic hemodialysis and EPO were enrolled. After stratification by 50th percentile of EPO response, the best predictive model was identified by backward elimination of the risk factors with the least contribution to the regression. Relationship between age, gender and EPO resistance was examined by analysis of covariance (ANCOVA). The most predictive model of EPO response for the pediatric cohort had, as the major variables, urea clearance x dialysis duration/total body water (Kt/V), urea reduction ratio (URR), intact parathyroid hormone (iPTH), blood loss, normalized protein catabolic rates (nPCR) and indices of malnutrition and inflammation, whereas adults had iron and folate deficiencies as the dominant variables. Although EPO resistance was more common in female subjects than in male subjects, relationship with neither age nor gender was significant. Furthermore, the prescription of a larger (initiating) EPO dose by pediatric physicians compared with adult nephrologists confounded the interaction between age and EPO resistance. In summary EPO resistance in the pediatric dialysis cohort was predicted by nutritional deficits, inflammation, poor dialysis, and hyperparathyroidism, while iron and folate deficits were the major determinants in adults. Although confounded by the pattern of EPO prescription, neither age nor gender was predictive of EPO resistance in the two study groups.

The common finding of hypokalemic alkalosis in several unrelated disorders may confound the early diagnosis of salt-losing tubulopathy (SLT). Antenatal Bartter syndrome (BS) must be considered in idiopathic early-onset polyhydramnios. Fetal megabladder in BS may allow its distinction from third-trimester polyhydramnios that occurs in congenital chloride diarrhea (CCD). Fetal megacolon occurs in CCD while fecal chloride &gt;90 mEq/L in infants is diagnostic. Failure-to-thrive, polydipsia and polyuria in early childhood are the hallmarks of classic BS. Unlike BS, there is low urinary chloride in hypokalemic alkalosis of intractable emesis and cystic fibrosis. Rarely, renal salt wasting may result from cystinosis, Dent disease, disorders of paracellular claudin-10b and Kir4.1 potassium-channel deficiency. Acquired BS may result from calcimimetic up-regulation of a calcium-sensing receptor or autoantibody inactivation of sodium chloride co-transporters in Sjögren syndrome. A relatively common event of heterozygous gene mutations for Gitelman syndrome increases the likelihood of its random occurrence in certain diseases of adult onset. Finally, diuretic abuse is the most common differential diagnosis of SLT. Unlike the persistent elevation in BS, urinary chloride concentration losses waxes and wanes on day-to-day assessment in patients with diuretic misuse.