搜索结果：Case reports in nephrology

Knowledge about a patient’s glomerular filtration rate (GFR) is central to the practice of medicine. It is needed to diagnose and classify chronic kidney disease (CKD), and helpful to establish prognosis [1]. In addition, it is used to decide when to start specific medication, how to dose medication and when to refer patients for specialist nephrology care or when to start kidney function replacement treatment. GFR can best be measured (mGFR) by injection of exogenous tracers, such as iothalamate and iohexol, and serial blood sampling. This is a relatively cumbersome and expensive technique, and is therefore only used in specific cases. In clinical practice, equations are used to estimate GFR (Fig. 1 and Table 1). These equations use readily available information about patient characteristics, such as age and sex, and about creatinine as an endogenous filtration marker. The oldest equation is the one developed by Cockcroft and Gault in 1976 [2]. It should be noted that their equation does not estimate GFR, but creatinine clearance. Creatinine clearance is determined not only by glomerular filtration of creatinine, but also by tubular secretion of creatinine. Tubular creatinine clearance can amount to up to 50% of total creatinine clearance, especially in subjects with impaired kidney function and obesity [3]. Consequently, the Cockcroft–Gault equation should not be used to estimate kidney function because it can overestimate GFR considerably. In that respect it is surprising that the summary of product characteristics for many drugs evaluated by regulatory agencies, even novel drugs, still refer to the Cockcroft–Gault creatinine clearance for dose adjustment [4]. The Modification of Diet in Renal Disease (MDRD) equation was developed in 1999 to improve prediction of GFR, which was a major step forward also because it was widely accepted [5, 6]. In 2009 it was replaced by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which was more accurate at higher GFR [7]. This latter equation has become the standard method for estimating GFR across the world. The development over time of the various GFR estimation equations, and their strengths and weaknesses. Oversight of the various equations to estimate kidney function. SCr, serum creatinine. Oversight of the various equations to estimate kidney function. SCr, serum creatinine. A problem with the 2009 CKD-EPI equation is that besides information on age, sex and creatinine, it also requires information on race. During recent years it has been argued that race is a social, political and legal rather than a biological construct, and that the incorrect use of race may have a negative effect on health equity [8]. The National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) announced therefore in 2021 that “race modifiers should not be included in equations used to estimate kidney function” and that “current race-based equations should be replaced by a substitute that is accurate, representative, unbiased, and provides a standardized approach to diagnosing kidney diseases” [9]. To achieve these goals the NKF and the ASN established a task force to reassess inclusion of race in the estimation of GFR in the USA. Why the race coefficient was developed and scientific drawbacks of using it have recently been reviewed by Delanaye et al. [10]. During the development of the CKD-EPI equation it was observed that the relationship between mGFR and serum creatinine was different in Black and White participants. It was argued that these divergent results may be explained by the difference in muscle mass between Black and White people. An African-American race coefficient was therefore introduced. The results for non-Blacks were to be multiplied by the factor 1.159 to obtain an estimated GFR (eGFR) value for African-Americans. A problem, however, might be the selection of Black people in the study that led to the 2009 CKD-EPI equation. As Delanaye et al. argue, the great majority of Black participants came from one study, the African American Study of Kidney Disease and Hypertension (AASK) [10]. Specific methodological aspects of this study could therefore have had a serious impact on the accuracy of the CKD-EPI equation for Black people. For instance, the body composition with respect to muscle mass of Black participants in the AASK study may not be representative for the overall Black population in the USA and elsewhere. Other theoretical reasons why serum creatinine may differ between Black and White people at a same level of GFR could be differences in tubular secretion of creatinine or a difference in the intake of meat as exogenous source of creatinine. It should be noted that these factors have all been poorly studied. In the wake of racial reckoning since the spring of 2020 in the USA, efforts have led to the examination of traditional medical algorithms that incorporate race modifiers [11]. Prominent among these efforts has been reconsideration of race-based adjustment in GFR estimation equations, and most important has been the initiative by the CKD-EPI research group. In 2021 these investigators developed new equations that do not use race, and compared their accuracy with that of their previous, 2009 CKD-EPI equation [12]. In their validation set which included 4050 subjects, of which 579 were Black individuals, the old 2009 CKD-EPI equation which uses sex, age, race and creatinine overestimated mGFR by 3.7 mL/min/1.73 m2 in Blacks and by 0.5 mL/min/1.73 m2 in non-Blacks. The new 2021 CKD-EPI equation that has no race coefficient performs slightly worse on a population level because it underestimated mGFR by 3.6 mL/min/1.73 m2 in Blacks and overestimated mGFR by 3.9 mL/min/1.73 m2 in non-Blacks. Thus, in Blacks the absolute bias in estimating mGFR is similar with the old and new equations, albeit the 3.7 mL/min/1.73 m2 overestimation has become a 3.6 mL/min/1.73 m2 underestimation. Although absolute bias may mathematically have remained similar in Blacks, this change from over- into underestimation will be important from a healthcare perspective, because it is expected to lead to, for instance, earlier referral for start of dialysis or kidney transplantation [13, 14]. The 2020 census showed that the US population consists of 12.4% Black and 87.6% non-Black subjects [15]. In the larger population of non-Blacks, the new 2021 CKD-EPI equation is less accurate, with an overestimation of now 3.9 instead of 0.5 mL/min/1.73 m2, whereas imprecision remained nearly similar (more than 10% of eGFR values are more than 30% different from mGFR) [12]. It was calculated that when adopting the 2021 CKD-EPI equation, the prevalence of CKD among Black persons will go up from 14.3% to 16.3%. In contrast, in non-Blacks it will go down from 11.7% to 10.3% [12]. The largest difference in accuracy in non-Blacks with the new versus the old CKD-EPI equation was found in subjects >65 years old, with an overestimation of mGFR by around 6 instead of around 1 mL/min/1.73 m2 [12]. For an individual, this bias is relatively small compared with the imprecision. The CKD-EPI investigators felt therefore that the change in accuracy was not meaningful. At a population level, however, these changes in bias can lead to important differences in CKD prevalence and risk prediction, with different results for Black and non-Black race groups. As a side note, the CKD-EPI also developed new equations based on cystatin C only, and on creatinine plus cystatin C. It was shown that the equation for cystatin C only did not perform better than the one for creatinine only [16], and that these combined equations performed slightly better than equations incorporating only creatinine or only cystatin C [12, 16]. Shortly after publication of these results, the NKF-ASN task force issued several recommendations, among which was to implement immediately for US adults the new 2021 CKD-EPI equation, which does not contain a race coefficient [17]. The slightly poorer performance of the new eGFR equation in non-Black people was apparently felt to be a reasonable price to pay to avoid the questionable race coefficient. In this issue of Nephrology Dialysis Transplantation (NDT) two original articles are published that test the 2021 CKD-EPI equation in European settings. The first investigated how well it performs to estimate GFR in various Black and White populations [18]. The second studied the impact of using 2021 CKD-EPI equation on CKD prevalence and prognostic accuracy [19]. Both studies are of interest for several reasons, among which because they report on large numbers of subjects, which renders these results robust. The results are also described in much detail, with an abundance of supplementary material made available to the readers, which allows an independent judgement. Also important is that they report on European or predominantly European populations, which may help guide European nephrology in deciding what to do with the new CKD-EPI equation. These two studies are described in the two paragraphs below. Delanaye et al. studied on behalf of the European Kidney Function Consortium (EKFC) the accuracy of the 2009 and 2021 CKD-EPI equations, as well as the accuracy of a GFR estimation equation that this consortium previously developed, the EKFC equation [18, 20]. This equation uses sex-, age- and race-specific median creatinine values obtained from healthy subjects to mathematically estimate GFR from a given serum creatinine value [20]. This study was performed in a relatively large population of 13 856 subjects (of which 1572 were Black) in whom GFR was measured with exogenous tracers. The authors found that in European Whites the accuracy of the 2021 CKD-EPI equation was lower than in non-Blacks in the publication by CKD-EPI. In fact, of the three equations tested, the accuracy of the 2021 CKD-EPI equation was the lowest, with an overestimation of mGFR by 6.0 mL/min/1.73 m2, followed by an overestimation by 3.0 mL/min/1.73 m2 by the 2009 CKD-EPI equation [18]. The best performance was noted for the EKFC equation, with a slight underestimation of 0.3 mL/min/1.73 m2 [18]. The authors offer several explanations for why the 2021 CKD-EPI equation performs less well in their study. First, an equation always performs better in the cohort in which it has been developed. This explanation can of course be used to plead against the CKD-EPI equation which was developed and tested by CKD-EPI, as well as for the EKFC equation which was developed and tested by the EKFC. Second, in the CKD-EPI development population the majority of studies used renal clearance of iothalamate as the gold standard to measure GFR, whereas the EKFC used various plasma clearance techniques. What the effect is of these differences in GFR measurements techniques in the development of CKD-EPI versus EKFC equations is as yet unknown, because the so-called gold standard techniques are unfortunately not well standardized nor validated against each other [21]. Third, the CKD-EPI equation considered non-Blacks as a whole, including Native American, Mexican, Asians and Hispanic people, whereas the non-Black populations in the EKFC equation was potentially more homogenous and more representative at least for the European population. The other original study published in this issue of NDT has been performed by Fu et al. [19]. These authors investigated how adopting the 2021 CKD-EPI equation would impact prevalence of CKD and risk prediction. Based on creatinine data of 1.6 million Stockholm adults with serum creatinine measurements available from routine healthcare between 2007 and 2019 (the SCREAM cohort, Stockholm CREAtinine Measurements), they showed that on average eGFR would go up by a median of 3.9 (interquartile range 2.9–4.8) mL/min/1.73 m2. Especially older individuals and males had a larger eGFR increase. Consequently, the population prevalence of CKD G3a–5 would decrease by around 25%, from 5.1% to 3.8%. Remarkably, the absolute decease in CKD prevalence was highest in participants ≥65 years old, and in those with diabetes or cardiovascular disease. This is surprising, because we know from clinical practice that these subgroups have a particularly high chance of progressive CKD. The clinical translation would be that fewer individuals are perceived as having a high cardiovascular risk based on their eGFR results. In addition, individuals reclassified to a higher eGFR based on the 2021 CKD-EPI equation exhibited a higher risk of all-cause/cardiovascular death and major adverse cardiovascular events than those not reclassified with a similar eGFR. Notwithstanding these results, the association of eGFR with kidney, cardiovascular and mortality outcomes did not differ significantly when using the 2021 CKD-EPI equation instead of the 2009 CKD-EPI equation. A limitation of this study is that no information on race was available. This may be a scientific limitation, but in clinical practice in nearly all countries across Europe the race coefficient is not used for the 2009 CKD-EPI equation because legally it is not permitted to collect data on ethnicity. Given the presently available data, the question is now what European nephrology should do with the new 2021 CKD-EPI equation—should it be adopted or ignored? There are compelling arguments to adopt it. We suggest that nephrology use the same language, definitions and equations across the globe. In 2019 KDIGO organized a Consensus Conference to make sure that we use uniform nomenclature to describe kidney function and disease. This helps effective communication by stakeholders in the kidney health community, and is instrumental to raise public awareness of the importance of CKD [22]. We would also favor that nephrology across the globe uses the same equations to estimate GFR. It would be awkward if a different equation were to be used in the USA from that used in Europe. This would impact the prevalence of CKD differentially. When intervention trials are designed, the inclusion and exclusion criteria with respect to kidney function may become different in the USA versus Europe. These are all issues that should be avoided. There are also convincing arguments against changing the CKD-EPI equation that is currently used in Europe. The first is that nearly all European countries do not use the race coefficient for the 2009 CKD-EPI equation. There is therefore no sense of urgency to change to the official race-free 2021 CKD-EPI equation. Another important reason is that the new equation does not perform better, but worse. Because GFR is overestimated in the larger part of the population, the overall CKD prevalence figures would decrease overnight. Also, the composition of the CKD population would change, since especially patients whom we previously thought of as high-risk patients are affected, i.e. males, elderly individuals, and subjects with a history of diabetes or cardiovascular disease. Would this imply that epidemiological studies that showed that especially these subjects are at risk of developing CKD and its complications might have to be redone? In addition, how should the abrupt changes in eGFR induced by adopting a new equation be explained to patients, general practitioners and other medical specialists? On an individual level, the substantial reclassification to higher eGFR categories may also have unwanted implications for medication initiation, discontinuation and dosing, and financial coverage, and may lead to later nephrologist referral, planning for dialysis and evaluation for kidney transplantation. Weighing the above arguments, we favor the opinion that, at the moment, European nephrology does not adopt the 2021 CKD-EPI equation to estimate GFR. When we want to change the existing equation, it should be a step forward. That does not seem to be the case now. Of course, we would like to align with our American colleagues, but at the same time it should be acknowledged that the dilemma of whether or not to adopt the 2021 CKD-EPI equation is caused by American nephrology, because ASN and NKF decided to change without consulting their counterparts in other parts of the world. In retrospect, that should have been done in consensus. European nephrology can therefore not be held accountable for inconsistencies when it now does not align. If European nephrology wants to make a real step forward in developing more accurate GFR estimation equations, there are three possible solutions. First, when creatinine is maintained as the sole kidney function marker to be used in CKD-EPI-like GFR estimation equations, anthropometrics could be included as additional covariates to adjust for interindividual differences in muscle mass, as the most important determinant of serum creatinine concentration besides kidney function. The older equations did not use weight and height as proxies for muscle mass because at that time such information was not routinely available for many patients in clinical chemistry labs. Nowadays, with the widespread use of electronic patient files, this information is stored and easy to use. But even weight and height may not be sufficient as proxies for muscle mass in an individual, as Hsu et al. pointed out recently [23]. What might work is when, alongside a standard GFR estimation equation, additional equations are developed for subjects with disproportionally low, and for subjects with disproportionally high muscle mass for their age and sex. Second, the type of equation could be changed. The equation that was developed by the EKFC works, and is an example of a fundamentally different approach. It uses so-called Q values, which are sex- and age-specific median creatinine values in healthy subjects, to estimate GFR for an individual. These Q values can be obtained for different populations (instead of different races) according to age and gender, for instance from large local hospital databases. The validation results by the EKFC are promising. Performance in terms of bias and accuracy seems better [18, 20], but external validation is needed, preferably by independent research groups using large datasets including populations from outside Europe. An advantage could also be that this equation can be used for all age groups, and not only for adults, as holds for the CKD-EPI equation (Table 1). A disadvantage could be that the eGFR results are dependent on the normal Q values that are used for various populations, because the selection of these normal values may have an arbitrary component. In addition, the EKFC equation has a standard Q value for Caucasian European males and females, and adjusts these Q values for other populations including Black individuals (Table 1). This is reminiscent of using the race conversion factor in the 2009 CKD-EPI equation, the issue which started the discussion about the to this equation. The Q values for the EKFC equation may therefore better be based on biological characteristics and not have an population. Third, we could change the from creatinine, or an to creatinine as marker for kidney function. In this respect cystatin C has most In to creatinine, cystatin C is by all and not only by serum concentration is therefore not dependent on muscle The CKD-EPI research showed that new eGFR equations that incorporate creatinine and cystatin but race, are more accurate and led to differences between Black participants and non-Black participants than new equations without race with creatinine the use of cystatin C or in with creatinine the association between eGFR and the of death and kidney across population cystatin C is not widely available for clinical use because not clinical chemistry its and because are in general higher than for serum creatinine also cystatin C is not independent of specific For instance, it is in obesity and and also cystatin C values of cystatin C has not yet been should therefore be made to make cystatin C available at lower and to improve its At the of cystatin C for GFR estimation is especially for subjects with muscle mass for their age and sex, and for subjects with an eGFR creatinine between and mL/min/1.73 m2 without to that these subjects have CKD. cystatin C other filtration have been such as and but as yet these have been poorly studied to be forward is to improve GFR we that we should only change to a novel equation when it has better We should not be by because changing our standard equations will discussion and and holds the that we with other that of their on eGFR When a change is we should to such a new GFR estimation equation. When nephrology uses the same or at least a similar equation around the this will have many for healthcare on an individual patient and on a population level, as well as for To avoid the incorrect use of race as a biological and the negative effect on health the novel 2021 CKD-EPI equation was not to a race coefficient. At European nephrology in general uses the 2009 CKD-EPI equation to estimate kidney function for all subjects, without the Black race coefficient that this equation an of changing from the 2009 to the 2021 CKD-EPI equation is therefore not felt to be an the 2021 CKD-EPI equation also seems to estimate GFR less than the 2009 CKD-EPI equation, by GFR in the larger part of the European population, there is no to adopt the new equation. European nephrology would do better to novel to improve GFR such as anthropometrics to estimation equations, fundamentally changing these GFR equations or other than creatinine as filtration When a in accuracy and bias is and validated efforts should be made to novel equations are to the and are of the of the European Renal is of Nephrology Dialysis Transplantation is of the European Renal is Renal of the is of is of the Kidney and is of the

The percutaneous renal biopsy (PRB) of native kidneys was introduced by Iversen and Brun (1) in 1951. Prior to this time, insight into clinicopathologic correlation was limited to information obtained through surgically obtained specimens or from evaluation at autopsy. The development of the PRB evolved from their experience with percutaneous liver biopsy using an aspiration-needle technique. Intravenous pyelography was used for localization of the right kidney (to avoid large vessels and the spleen), and the patient was biopsied in the sitting position. Unfortunately, the success of their technique was limited, with adequate tissue obtained in only 53% of biopsies (1). Concerned with the poor technical success using this technique, Drs. Robert Kark and Robert Muehrcke (2), my predecessors at Rush University Medical Center, made important modifications to the procedure (2–5). First, they performed the biopsy with the patient in the prone position and placed a sandbag under the abdomen, because they felt this would reduce the “mobility” of the kidney. Second, instead of an aspiration biopsy needle, they used a Franklin-modified Vim-Silverman needle, a precursor to the needle currently used today, which trapped the tissue in the needle and then sheared it off. In 1954, Kark and Muehrcke (2,3,5) published their experience with this “new technique,” reporting a success rate of 96% and no major complications. Kark and Muehrcke realized the value of the renal biopsy would be to provide the nephrologist with information that would be critical in diagnosis, prognosis, and guiding therapy. In their initial study, they found that the biopsy findings changed the initial clinical diagnosis in more than 50% of cases (2). Additionally, they felt that renal biopsy would provide nephrologists with the ability to follow the natural history of renal disease through repeated biopsies, define new renal diseases, and assess the effects of therapy on renal disease. Almost 60 years later, these predictions have proven true. The renal biopsy, developed by nephrologists, has become an integral part of the clinical practice of nephrology and in the research of renal disease. In fact, the development of the PRB has been considered one of the major technological advancements that led to the establishment of nephrology as a subspecialty in 1960 (6). The success of the PRB is defined not only by the ability to attain adequate tissue for diagnosis but, equally important, the safety profile of the procedure. Throughout the years, improvements in imaging techniques and biopsy needles have resulted in the ability to obtain adequate renal tissue for diagnosis in >95% of renal biopsies (7–11). Additionally, these technical improvements have led to increased safety of the procedure: the rate of complications resulting in death decreased from 0.12% to 0.02% during the last 50 years (7,12). In fact, during the last 20 years, death resulting from PRB of native kidneys has been an extremely rare event, with no deaths reported in a number of recent studies (13–20). Nonetheless, despite the improved safety of the procedure, clinically significant bleeding complications do occur in 4%–7% of biopsies on average (7,12), and rates as high as 25% to >30% have been reported in a number of recent studies despite the use of newer technologies (8,14,19,21). Although the majority of complications resolve spontaneously without the need for further intervention, in up to 9% of biopsies, the complication can be more severe and potentially life threatening, resulting in the need for intervention (7,11,12,22). In most cases, this may be simply the transfusion of blood products, but the need for more invasive intervention such as surgery or angiography and embolization, although uncommon, still occurs in up to 0.8% of biopsies even in recent reports (7,8,11,12,21). Differences in complication rates among studies can vary substantially and can be difficult to interpret because of confounding issues such as the nature of the study (prospective or retrospective), the type of imaging used (real-time ultrasound, computerized tomography, or blind biopsies after ultrasound localization), the needle type or gauge used (manual versus automated and 14, 16, or 18 gauge), and who is performing the biopsy (a few “experienced” nephrologists, many nephrologists, renal fellows, or radiologists) (7,12). Additionally, the reason for biopsy and patient mix can be important because studies that comprise high-risk patients, those with renal insufficiency, poorly controlled hypertension, or a prolonged bleeding time/coagulopathy, are more likely to report increased complication rates (11,14,20,21,23–27). In this issue of CJASN, Tondel et al. (28) report on the 22-year experience (from 1988 to 2010) with PRB of native kidneys from the Norwegian Kidney Biopsy Registry, which includes 26 hospitals. The 9288 percutaneous biopsies in the study represented 96% of all biopsies performed during that time period. Adults comprised 92% of biopsies, and 98% were performed under ultrasound guidance (it is not clear whether this was real-time ultrasound). Although the primary reason for biopsy was proteinuria (81%), a large proportion of biopsies were done in patients with renal insufficiency with an estimated GFR (eGFR) of <60 ml/min per 1.73 m2 in 63% of the patients and <30 ml/min per 1.73 m2 in 37% of patients. Despite this relatively high-risk patient population, there were no biopsy-related deaths, and only 2.6% of biopsies were associated with a complication. A major complication (defined by the need for a blood transfusion, surgery, or radiologic intervention) was reported in only 0.9% of biopsies. Blood transfusions were required in 0.9% of cases, and surgical or radiographic intervention (angiography with or without embolization) was required in 0.2% of cases. By multivariate analysis, only the eGFR at the time of biopsy and the number of biopsies performed by a center per year were predictive of complication rate. Patients with an eGFR of 59–30 ml/min per 1.73 m2 had five times the risk of a complication, and patients with an eGFR of <30 ml/min per 1.73 m2 had an almost 16-fold greater risk for a complication compared with patients with an eGFR of ≥60 ml/min per 1.73 m2. Additionally, centers that performed <30 biopsies per year had a 1.6-fold greater likelihood of complication than centers performing >30 biopsies per year. Although there was no difference in the complication rate based on who performed the biopsy (nephrologist or radiologist) or the needle size (14, 16, or 18 gauge), it is of interest that radiologists performed the biopsy in 54% of cases, with nephrologists performing only 33% of biopsies. Also, 62% of biopsies were done using an 18-gauge needle, and only 14% were done with a 14-gauge needle. Adequate tissue for diagnosis was obtained in 94% of cases overall, and there was no difference based on who performed the biopsy or needle size. Nonetheless, 3% of biopsies had no glomeruli, and the sample size was significantly smaller in biopsies done with 18-gauge needles (a median of 9 glomeruli per biopsy) compared with 12 glomeruli with either the 16- or 14-gauge needles. Over the 22-year period, there was a decrease in both the number of biopsies done by nephrologists (actual proportion not provided) and the proportion of biopsies done using 14-gauge needles (22% to ≤1%). This important study by Tondel et al. (28) reconfirms that the PRB is a safe and successful procedure in a nationwide experience. However, it also serves as a wake-up call for the nephrology community that smaller biopsy needles are being used, and biopsies are increasingly being performed by radiologists rather than nephrologists. Since the introduction of the automated needles, there has been a tendency to use smaller 18-gauge needles rather than the larger 14-gauge needles, which had been the common practice with manual needles (7,12). The rationale for this is not clear but may be linked to the increasing number of biopsies being done by radiologists as suggested by the study of Tondel et al. (28) and as reported by Gupta and Balogun (29), who found that an 18-gauge needle was used in 69% of biopsies performed by radiologists compared with only 14% of biopsies performed by nephrologists. Additionally, the study by Tondel et al. (28) and other studies (7,29–32) continue to demonstrate that when using an 18-gauge needle, the sample size is significantly smaller (9 versus >12 glomeruli), and often, the quality of the sample (the number of intact glomeruli) is poorer. In the only study assessing the differences between 14-, 16-, and 18-gauge automated needles, Nicholson et al. (32) demonstrated that using an 18-gauge needle resulted not only in a significantly smaller sample size (9 versus 11 versus 15 glomeruli) but was also associated with less diagnostic success (53% versus 76% versus 85%), despite no significant differences in complication rates. The importance of sample size cannot be underestimated when evaluating glomerular lesions that are focal in nature and whose prognosis depends on the degree of involvement (i.e., focal segmental glomerulosclerosis, lupus nephritis, vasculitis, and crescentic GN) (33,34). A biopsy containing only 10 glomeruli has a 35% probability of missing the lesion if the prevalence of diseased glomeruli in the kidney is 10%, but the probability decreases to 12% if 20 glomeruli are contained in the biopsy. Thus, the trend toward an increasing use of 18-gauge needles stands to jeopardize the diagnostic accuracy of the PRB. There has also been a shift in who is performing the biopsy during the last 20 years. In 1990, Tape et al. (35) published a survey of 516 practicing nephrologists trained from 1964 to 1974 and found that 95% of certified nephrologists performed PRB. Five years after this report, a memorandum from the Renal Physicians Association found that 35% of percutaneous renal biopsies were now being performed by radiologists. So disturbing was this finding that in his presidential address to the American Society of Nephrology in 1998, Dr. Wadi Suki voiced his concern that the shift from nephrologists to radiologists in performing the PRB could undermine the nephrologist's status as a subspecialist (36). In a recent report from 2011, it was found that only 55% of nephrologists are performing renal biopsies in Australia (37). Unfortunately, the reasons that fewer nephrologists are performing renal biopsies have been attributed to a number of issues including reimbursement, liability, inconvenience, and increasing workload (27,29). The declining trend in the performance of PRB by practicing nephrologists should be alarming to all of us and especially to those of us who are involved with training fellows. As nephrologists, we have a vested interest in the biopsies we perform that is not shared by radiologists, because the information provided by this procedure directly affects the care we provide our patients. As a result, in training our fellows, we must emphasize the importance of performing renal biopsies as part of the practice of nephrology. We need to provide our fellows with an experience that makes them competent and comfortable performing this procedure so they will continue to incorporate it into their clinical practice. Given the increased demands on those nephrologists in private practice, the time may have come that these practices consider allocating biopsies to either a single nephrologist within their groups or to incorporate an interventional nephrologist into their practice. Alternatively, nephrologists should consider referring patients for biopsy to university programs that provide renal biopsy services, as well as outstanding nephropathologic support. Otherwise, as shown by the Norwegian experience, the PRB, a procedure so important in the development of our subspecialty, is in jeopardy of being lost along the way. Disclosures None.

Contrary to predictions in the Gottschalk report to the US Congress in 1960 that the projected incidence of new end-stage renal disease patients will be on the order of 20 new patients per year, this number has been exceeded tenfold, mainly because no one anticipated the increase of elderly patients being accepted for dialysis. According to the US Renal Data System 2000 Annual Data Report, the mean age at the initiation of dialysis was 61 yr, and the fastest-growing group was patients 75 yr of age and older (1). Similar findings have been reported from other Western countries (2,3 ). These data suggest that ESRD has become a geriatric illness and that, in the 21st century, nephrologists will be forced to practice mainly geriatric medicine as amateur geriatricians, having only limited knowledge of the special challenges posed by the elderly. To provide appropriate care to these patients, one should keep in mind that they face not only medical but also social problems. These include accurate diagnosis and on-time referral, multiple comorbidity, optimal mode of therapy, quality of life, and ethical and social issues. In this context, the study of Jolly et al. (4), reported in this issue of JASN, is welcome because it highlights one important and sensitive issue: that of offering or withholding dialysis from octogenarians with ESRD and the consequences of such a decision. The authors present a single-center cohort of 146 octogenarians referred over a 12-yr period and, for the first time in the literature, compare the results of actively treated patients with those from whom dialysis was withheld and who were managed conservatively. Dialysis was withheld from 29% of patients. The decision to withhold was made mainly by the nephrology team in 86% of patients; in only 14% was the decision made by the patient himself or herself. The presence of low Karnofsky scores (KS), social isolation, and late referral were the most important factors that influenced the nephrology team’s decision to propose conservative treatment. Median survival of dialyzed patients was 28.9 mo, which is one quarter to one third of their normal life expectancy at that age. Not surprisingly, survival of dialyzed patients was significantly higher than that of non-dialyzed (8.9 mo). One-year mortality was predicted by three significant covariates (body mass index [BMI], referral time, and Karnofsky score [functional dependence]) and was 15% in the low-risk group (early referred, BMI = 22, KS > 40) and 83% in the high-risk group (late referred, BMI = 18, KS < 40). These investigators have provided us with some valuable information: (1) one can observe excellent results if octogenarians are accepted for dialysis; (2) conservative treatment yields poor results; (3) there are identifiable factors influencing the decision-making process; and (4) some of the independent risk factors that predict outcome may be modifiable. Now one can use their outcome findings (a and b) whenever one is discussing dialysis options with octogenarian patients with ESRD. Early referral was associated with higher acceptance into the dialysis program and a better prognosis. It has been recognized before that early mortality (first 90 d) is high among the elderly ESRD population (27% for those over 85 yr) and that late referral to nephrology units is significantly related to early death (5), longer initial hospitalization, and greater frequency and longer duration of subsequent hospital admissions (6,7 ). It should be noted, however, that it is often not that the elderly are not referred early but that the nephrologists may delay the initiation of dialysis because of misleading serum creatinine levels. Therefore, NKF-DOQI guidelines recommend that one use calculated weekly creatinine clearance when making decisions about the initiation of dialysis (8). Furthermore, one should consider initiation of dialysis before uremic symptoms become overt and malnutrition evident (9). Unfortunately, some primary-care physicians still use age as a criterion for referring these patients to the nephrologist for dialysis. A recent study showed that only 65% of US and Canadian physicians and an even lower percentage (49%) of British physicians would refer elderly patients to a nephrologist for dialysis irrespective of age (10). Another important issue is the decision-making process for offering or withholding dialysis after the attending physician has decided on referral to a nephrologist. Healthcare professionals cannot make this decision for others; instead, they should advise patients, sharing with them their knowledge and experience without projecting their own prejudices. Joly et al. clearly show the consequence of withholding dialysis and emphasize the need for guidelines when discussing dialysis options with such patients. Fortunately, the American Society of Nephrology and the Renal Physicians Association published evidence-based guidelines in 2000 (11), which emphasize that only informed patients or their surrogates should make the final decisions (12). If a conflict exists between provider and patient/family, the provider should fall back on established ways of conflict resolution rather than imposing arbitrary decisions and confrontation. It sometimes takes a long time to come to a satisfactory decision for the patient/family, but it is time well spent. Guidelines recommend against offering dialysis to patients with a known and advanced terminal illness or those who have serious mental impairments as a results of stroke, Alzheimer disease, or neurologic dysfunction. When neither the medical team nor the patient or family member can decide whether or not to dialyze, the patient should be offered a trial period of dialysis of 30 to 90 d. Another important point regarding the factors that influence decision-making about dialysis is that some of these factors may be reversible. Joly et al., who used the Karnofsky scale (physical dependency) to measure activity level, show that a low score is a poor predictor of outcome. Although quality of life does not always depend on the patient’s physical state, these findings emphasize the importance of physical activity, which may be improved by control of anemia with EPO and specially designed rehabilitation programs either before or during dialysis (13). Social isolation was also a significant predictor for withholding dialysis. Better social support is of great importance to the increasing number of elderly who need assisted care. Even the most complicated cases, i.e., those with mental and physical disability and without family support, should not be automatically refused treatment; with a broad network of medical and social support, home-care nursing, and rehabilitation programs, these patients can improve and take on the burden of dialysis if they so desire. Alternatively, dialysis can be provided in a long-term care facility (14). There are many unanswered questions about the management of elderly with ESRD, such as optimal mode of therapy, modality-related complications, quality of life, and survival on various dialysis modalities. The answers to all of these require well-designed, prospective studies on large series of patients. For us, the most important is whether dialysis is worth starting in the elderly, particularly in octogenarians. Joly et al. have confirmed that survival of those treated with dialysis is satisfactory and is significantly better than in those treated conservatively. These findings should be presented to all those caring for such patients, especially to the primary-care physician but also to the public at large. It is now clear that octogenarians can be effectively treated by dialysis. No one can discuss dialysis in the elderly without considering the financial implications of such a decision. As Joly et al. say, no one has imposed explicit restrictions on the provisions of dialysis to those in need irrespective of age, nor do such restrictions exist in the United States or any other developed country. Governments usually avoid such explicit orders, especially now that the elderly have become a political force; instead, they impose restrictions by covert means, such as restricting the use of dialysis stations or nephrology positions, or reducing reimbursement or including dialysis costs in the global budget of the hospitals, and so on. Governments also restrict access by emphasizing the social responsibilities of the physicians vis à vis their responsibility to the patient, expecting them to look at the bottom line, thus making them gatekeepers. Because they cannot do it openly, physicians who respond to such pressures may say that dialysis in the elderly is futile. This in reality is rationing. We believe that physicians have a primary responsibility to their patients and should never betray their trust. Under the present climate of cost consciousness, physicians in general and nephrologists in particular should speak up and advocate for their elderly patients, because no one else will do it for them. We believe that the publication of the article by Joly et al. will stimulate further discussion about the needs and rights of the elderly with end-stage renal disease and that geriatric nephrology will be taken more seriously in the future. We hope that the 7th International Conference on Geriatric Nephrology that will take place in Atlanta, GA, October 9–12, will be able to establish the subspecialty of Geriatric Nephrology to serve the increased number of elderly patients with ESRD who need our care. Note:For more information on the 7th International Conference on Geriatric Nephrology, contact Dr. Nancy Kutner at [email protected]

[This retracts the article DOI: 10.1155/2014/243746.].

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. METHODS: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. FINDINGS: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1-4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0-8·4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6-9·2) for males and 6·5% (5·4-7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs s1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-harm and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). INTERPRETATION: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury. FUNDING: Bill & Melinda Gates Foundation.

A literature review performed by the EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup highlighted deficiencies in the existing literature, especially the reporting of case studies. Although general reporting guidelines exist for case studies, there are none in the specific field of extracorporeal treatments in toxicology. Our goal was to construct and propose a checklist that systematically outlines the minimum essential items to be reported in a case study of poisoned patients undergoing extracorporeal treatments. Through a modified two-round Delphi technique, panelists (mostly chosen from the EXTRIP workgroup) were asked to vote on the pertinence of a set of items to identify those considered minimally essential for reporting complete and accurate case reports. Furthermore, independent raters validated the clarity of each selected items between each round of voting. All case reports containing data on extracorporeal treatments in poisoning published in Medline in 2011 were reviewed during the external validation rounds. Twenty-one panelists (20 from the EXTRIP workgroup and an invited expert on pharmacology reporting guidelines) participated in the modified Delphi technique. This group included journal editors and experts in nephrology, clinical toxicology, critical care medicine, emergency medicine, and clinical pharmacology. Three independent raters participated in the validation rounds. Panelists voted on a total of 144 items in the first round and 137 items in the second round, with response rates of 96.3% and 98.3%, respectively. Twenty case reports were evaluated at each validation round and the independent raters' response rate was 99.6% and 98.8% per validation round. The final checklist consists of 114 items considered essential for case study reporting. This methodology of alternate voting and external validation rounds was useful in developing the first reporting guideline for case studies in the field of extracorporeal treatments in poisoning. We believe that this guideline will improve the completeness and transparency of published case reports and that the systematic aggregation of information from case reports may provide early signals of effectiveness and/or harm, thereby improving healthcare decision-making.

Amidst the rising tide of chronic kidney disease (CKD) burden, the global nephrology workforce has failed to expand in order to meet the growing healthcare needs of this vulnerable patient population. In truth, this shortage of nephrologists is seen in many parts of the world, including North America, Europe, Australia, New Zealand, Asia and the African continent. Moreover, expert groups on workforce planning as well as national and international professional organizations predict further reductions in the nephrology workforce over the next decade, with potentially serious implications. Although the full impact of this has not been clearly articulated, what is clear is that the delivery of care to patients with CKD may be threatened in many parts of the world unless effective country-specific workforce strategies are put in place and implemented. Multiple factors are responsible for this apparent shortage in the nephrology workforce and the underpinning reasons may vary across health systems and countries. Potential contributors include the increasing burden of CKD, aging workforce, declining interest in nephrology among trainees, lack of exposure to nephrology among students and residents, rising cost of medical education and specialist training, increasing cultural and ethnic disparities between patients and care providers, increasing reliance on foreign medical graduates, inflexible work schedules, erosion of nephrology practice scope by other specialists, inadequate training, reduced focus on scholarship and research funds, increased demand to meet quality of care standards and the development of new care delivery models. It is apparent from this list that the solution is not simple and that a comprehensive evaluation is required. Consequently, there is an urgent need for all countries to develop a policy framework for the provision of kidney disease services within their health systems, a framework that is based on accurate projections of disease burden, a full understanding of the internal care delivery systems and a framework that is underpinned by robust health intelligence on current and expected workforce numbers required to support the delivery of kidney disease care. Given the expected increases in global disease burden and the equally important increase in many established kidney disease risk factors such as diabetes and hypertension, the organization of delivery and sustainability of kidney disease care should be enshrined in governmental policy and legislation. Effective nephrology workforce planning should be comprehensive and detailed, taking into consideration the structure and organization of the health system, existing care delivery models, nephrology workforce practices and the size, quality and success of internal nephrology training programmes. Effective training programmes at the undergraduate and postgraduate levels, adoption of novel recruitment strategies, flexible workforce practices, greater ownership of the traditional nephrology landscape and enhanced opportunities for research should be part of the implementation process. Given that many of the factors that impact on workforce capacity are generic across countries, cooperation at an international level would be desirable to strengthen efforts in workforce planning and ensure sustainable models of healthcare delivery.

OBJECTIVE: The ItalKid Project is a prospective, population-based registry that was started in 1990 with the aim of assessing the epidemiology of childhood chronic renal failure (CRF), describing the natural history of the disease, and identifying factors that influence its course. This article reports the epidemiologic results. METHODS: Prevalent and incident cases of CRF in children and adolescents were identified throughout Italy (total population base: 16.8 million children) by regularly asking all of the pediatric hospitals and adult nephrology units potentially involved in caring for children with kidney disease to report all cases that meet the inclusion criteria and then to update the clinical information regarding all previously reported patients on an annual basis. The inclusion criteria were 1) creatinine clearance (Ccr; according to Schwartz's formula) <75 mL/min/1.73 m2 bsa (predialysis) and 2) an age of <20 years at the time of registration. RESULTS: By December 31, 2000, 1197 patients (803 boys) had been registered. The mean incidence was 12.1 cases per million (range: 8.8-13.9), and the (point) prevalence was 74.7 per million of the age-related population. The mean age at registration was 6.9 +/- 5.4 years, and the mean Ccr was 41.7 +/- 20.5 mL/min/1.73 m2. The leading causes of CRF were hypodysplasia associated with urinary tract malformations (53.6%) and isolated hypodysplasia (13.9%), whereas glomerular disease accounted for as few as 6.8%. Hypodysplasia associated with primary vesicoureteral reflux (VUR) alone was responsible for as many as 25.8% of the cases, thus being the leading single cause with a female-to-male ratio of 1:3.2. The diagnosis of VUR was established early in life at an overall median age of 3 months (range: 0-180). However, the diagnosis was made significantly later among girls, whose median age at diagnosis was 9 months (range: 0-156; 95% confidence interval: 21.2-49.3) as against 2 months among boys (range: 0-180; 95% confidence interval: 10.9-21.2). As many as 23.6% of the registered patients had at least 1 severe associated disease (excluding urological abnormalities). A steep decline in renal survival occurred during puberty and early postpuberty, leading almost 70% of the patients to end-stage renal failure by the age of 20 years. When the population was subdivided on the basis of Ccr at the time of registration, the probability of kidney survival at 20 years of age was significantly different, being 63% in patients with mild renal failure (Ccr 51-75 mL/min), 30% in those with moderate renal failure (Ccr 25-50 mL/min), and 3% in those with severe renal failure (Ccr <25 mL/min). The incidence of renal replacement therapy was 7.3/y/100 patients, and the case-fatality rate on conservative treatment was 1.41%. CONCLUSIONS: This study provides important and recent epidemiologic information concerning CRF in children and adolescents: a mean annual incidence of 12.1 new patients per million of the age-related population with a very high proportion (57.6%) of hypodysplastic renal diseases with or without urinary tract malformation. By the age of 20 years, the cumulative probability of end-stage renal disease in the population as a whole was 68%. The probability of kidney survival sharply declined during puberty and early postpuberty. This is the first prospective evaluation of the incidence and outcome of CRF in children, including those with mild and moderate renal impairment.

The integration of large language models (LLMs) into healthcare, particularly in nephrology, represents a significant advancement in applying advanced technology to patient care, medical research, and education. These advanced models have progressed from simple text processors to tools capable of deep language understanding, offering innovative ways to handle health-related data, thus improving medical practice efficiency and effectiveness. A significant challenge in medical applications of LLMs is their imperfect accuracy and/or tendency to produce hallucinations-outputs that are factually incorrect or irrelevant. This issue is particularly critical in healthcare, where precision is essential, as inaccuracies can undermine the reliability of these models in crucial decision-making processes. To overcome these challenges, various strategies have been developed. One such strategy is prompt engineering, like the chain-of-thought approach, which directs LLMs towards more accurate responses by breaking down the problem into intermediate steps or reasoning sequences. Another one is the retrieval-augmented generation (RAG) strategy, which helps address hallucinations by integrating external data, enhancing output accuracy and relevance. Hence, RAG is favored for tasks requiring up-to-date, comprehensive information, such as in clinical decision making or educational applications. In this article, we showcase the creation of a specialized ChatGPT model integrated with a RAG system, tailored to align with the KDIGO 2023 guidelines for chronic kidney disease. This example demonstrates its potential in providing specialized, accurate medical advice, marking a step towards more reliable and efficient nephrology practices.

INTRODUCTION: Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. METHODS: Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. RESULTS: The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. CONCLUSION: We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

High-technology medicine saves lives and produces waste; this is the case of dialysis. The increasing amounts of waste products can be biologically dangerous in different ways: some represent a direct infectious or toxic danger for other living creatures (potentially contaminated or hazardous waste), while others are harmful for the planet (plastic and non-recycled waste). With the aim of increasing awareness, proposing joint actions and coordinating industrial and social interactions, the Italian Society of Nephrology is presenting this position statement on ways in which the environmental impact of caring for patients with kidney diseases can be reduced. Due to the particular relevance in waste management of dialysis, which produces up to 2 kg of potentially contaminated waste per session and about the same weight of potentially recyclable materials, together with technological waste (dialysis machines), and involves high water and electricity consumption, the position statement mainly focuses on dialysis management, identifying ten first affordable actions: (1) reducing the burden of dialysis (whenever possible adopting an intent to delay strategy, with wide use of incremental schedules); (2) limiting drugs and favouring "natural" medicine focussing on lifestyle and diet; (3) encouraging the reuse of "household" hospital material; (4) recycling paper and glass; (5) recycling non-contaminated plastic; (6) reducing water consumption; (7) reducing energy consumption; (8) introducing environmental-impact criteria in checklists for evaluating dialysis machines and supplies; (9) encouraging well-planned triage of contaminated and non-contaminated materials; (10) demanding planet-friendly approaches in the building of new facilities.

BACKGROUND: Serum creatinine concentration is an unreliable and insensitive marker of chronic kidney disease (CKD). To improve CKD detection, the Australasian Creatinine Consensus Working Committee recommended reporting of estimated glomerular filtration rate (eGFR) using the four-variable Modification of Diet in Renal Disease (MDRD) formula with every request for serum creatinine concentration. The aim of this study was to evaluate the impact of automated laboratory reporting of eGFR on the quantity and quality of referrals to nephrology services in Southeast Queensland, Australia. METHODS: Outpatient referrals to a tertiary and regional renal service, and a single private practice were prospectively audited over 3-12 months prior to and 12 months following the introduction of automated eGFR reporting and concomitant clinician education. The appropriateness of referrals to a nephrologist was assessed according to the Kidney Check Australia Taskforce (KCAT) criteria. Significant changes in the quantity and/or quality of referrals over time were analysed by exponentially weighed moving average (EWMA) charts with control limits based on +/-3 standard deviations. RESULTS: A total of 1019 patients were referred to the centres during the study period. Monthly referrals overall increased by 40% following the introduction of eGFR reporting, and this was most marked for the tertiary renal service (52% above baseline). The appropriateness of nephrologist referrals, as adjudicated by the KCAT criteria, fell significantly from 74.3% in the 3 months pre-eGFR reporting to 65.2% in the 12 months thereafter (P < 0.05). Nevertheless, a greater absolute number of CKD patients were appropriately being referred for nephrologist review in the post-eGFR period (24 versus 15 per month). Patients referred following the introduction of eGFR were significantly more likely to be older (median 63.2 versus 59.3 years, P < 0.05), diabetic (25 versus 18%, P = 0.05) and have stage 3 CKD (48% versus 36%, P < 0.01). CONCLUSION: The introduction of automated eGFR calculation has led to an overall increase in referrals with a small but significant decrease in referral quality. The increase in referrals was seen predominantly in older and diabetic patients with stage 3 CKD and appeared to result in net benefit.

BACKGROUND: Children's renal biopsy data were gathered for 3 consecutive years (1992-1994) by the Group of Renal Immunopathology of the Italian Society of Pediatric Nephrology, which opened a paediatric section of the Italian Registry of Renal Biopsies. MATERIALS: The Registry recorded the histological diagnosis and the clinical data at renal biopsy of 432 children < or = 15 years old (mean age 8.96 +/- 3.7 years). RESULTS: The most common glomerulonephritis (GN) at renal biopsy was idiopathic IgAGN (18.8%) and the most frequent secondary GN was Henoch-Schönlein purpura (HSP) nephritis (11.6%). Minimal-change disease (MCD) accounted for 11.6%, focal and segmental sclerosis (FSG) 8.5%, mesangial proliferative GN (MPGN) 9.5%, membranoproliferative GN 5.5%, and thin-membrane disease 5%. Lupus nephritis was diagnosed in 5% and Alport's GN in 3.9% of the cases. The annual incidence of primary GN in Italian children was 11.1 cases per million children population (p.m.c.p.), IgAN accounting for 3.1 cases, MCD 2.3, and HSP nephritis 1.9 cases p.m.c.p. respectively. Italian children underwent renal biopsy because of isolated microscopic haematuria in 19.3% of the cases, non-nephrotic proteinuria with or without microscopic haematuria in 31.2%, and nephrotic-range proteinuria in 34.2%, less frequently (15.3%) because of acute or chronic renal failure. Children with persistent isolated microscopic haematuria had most frequently IgAN (34.9%) or thin-membrane disease (25.3%), while those with non-nephrotic proteinuria had IgAN (30.4%) and HSP nephritis (23%). In cases with nephrotic proteinuria renal biopsy showed MCD in 34.5% of the cases, FSG in 16.9%, and MPGN in 12.2%. When renal biopsy was performed in chronic renal failure, chronic interstitial renal disease was detected in 62.5% of the cases. CONCLUSIONS: This National Registry provides data on the indications for performing renal biopsy in Italian children and on the frequency and annual incidence of histological lesions detected. IgAN, primary or related to HSP, was the most common nephritis in Italian children undergoing renal biopsy.

Mild and moderate vesicoureteral reflux is expected to resolve spontaneously in most children treated medically; however, maximum benefit or minimum risk of such therapy has not been defined. A prospective 5-year followup study of infants and children younger than 5 years at entry with primary vesicoureteral reflux (grades I to III/V) and radiographically normal kidneys after the first recognized urinary tract infection was initiated in 1984. A total of 113 patients was entered from 5 centers and 61% of the patients were less than 2 years old. Vesicoureteral reflux was unilateral in 65 cases (58%) and bilateral in 48 (42%). Of the 226 renal units reflux was grade IV in 4 (2%), III in 51 (22%), II in 81 (36%) and I in 25 (11%), and 65 (29%) had no vesicoureteral reflux. Data on 59 patients who have completed the protocol were analyzed for this report. Breakthrough urinary tract infection occurred in 20 patients. Of the 84 ureters with vesicoureteral reflux at diagnosis reflux resolved in 67%, and it was of lower grade in 22%, same grade in 8% and higher grade in 2%. Grade I vesicoureteral reflux resolved in 82%, grade II in 80% and grade III in 46% of the ureters. Resolution was better when vesicoureteral reflux was unilateral left (74%) than unilateral right (46%) or bilateral (60%). Renal scarring occurred, on average, in 10% of the kidneys without known vesicoureteral reflux or exposed only to nondilating (grades I and II) reflux and in 28% of those with dilating (grade III) reflux. Thirteen cases had breakthrough urinary tract infection but only after the scar was noted in 5. We conclude that under good medical management during 5 years of followup, even mild and moderate vesicoureteral reflux can be associated with renal injury.

BACKGROUND: More than 2 years have passed since the proposal of the diagnostic criteria for IgG4-related kidney disease (IgG4-RKD). The aim of this study was to estimate the number of histological diagnosis for IgG4-RKD throughout Japan and to clarify the regional distribution of the development of this disease. METHODS: A questionnaire was supplied to 140 research facilities registered in the Japan Renal Biopsy Registry (J-RBR). The items of the questionnaire were the total number of renal biopsies performed and the number of cases diagnosed as IgG4-RKD in 2012 and 2013 at each facility. Age, sex, and diagnosis category were also included for the IgG4-RKD cases. The geographic distribution of the disease development was evaluated using clinical case reports presented at the Eastern/Western regional meeting of the Japanese Society of Nephrology during the 15 years following 2001. RESULTS: Forty-seven facilities completed the questionnaire, resulting in a collection rate of 34 %. The total numbers of renal biopsies in 2012 and 2013 were 3387 and 3591, respectively. Forty-seven of these cases (24 in 2012 and 23 in 2013) were diagnosed as IgG4-RKD. The frequency of development of IgG4-RKD per one million over 40-year-old individuals during these 15 years varied between 0.9 and 3.1, depending on Japanese geographic region of Japan. CONCLUSION: The results of the present survey indicate that the number of diagnosis for IgG4-RKD is approximately 130 cases per year throughout Japan, and no regional differences in disease frequency appear to exist.

There have been tremendous advances during the last decade in methods for large-scale, high-throughput data generation and in novel computational approaches to analyze these datasets. These advances have had a profound impact on biomedical research and clinical medicine. The field of genomics is rapidly developing toward single-cell analysis, and major advances in proteomics and metabolomics have been made in recent years. The developments on wearables and electronic health records are poised to change clinical trial design. This rise of 'big data' holds the promise to transform not only research progress, but also clinical decision making towards precision medicine. To have a true impact, it requires integrative and multi-disciplinary approaches that blend experimental, clinical and computational expertise across multiple institutions. Cancer research has been at the forefront of the progress in such large-scale initiatives, so-called 'big science,' with an emphasis on precision medicine, and various other areas are quickly catching up. Nephrology is arguably lagging behind, and hence these are exciting times to start (or redirect) a research career to leverage these developments in nephrology. In this review, we summarize advances in big data generation, computational analysis, and big science initiatives, with a special focus on applications to nephrology.

BACKGROUND Tumor lysis syndrome is common in hematological malignancy, but less frequent in chronic and solid tumors. Almost always it is observed after chemotherapy or radiotherapy initiation, but rarely occurs spontaneously. CASE REPORT A 89-year-old female with stable chronic lymphocytic leukemia was admitted to the hospital because of worsening dyspnea and dry cough. Her vital signs were normal, except for sinus tachycardia. On physical examination, she appeared distressed, dyspneic, sweaty but afebrile, anxious, but alert and well oriented. Lung examination revealed reduced air entry with bibasilar crackles. No peripheral edema was seen, pulses were normal, and no signs of deep vein thrombosis were observed. Laboratory analysis revealed leukocytosis; but normal hematological and biochemical parameters. Intravenous (IV) furosemide and antibiotics (IV ceftriaxone and orally azithromycin) were started along with steroid therapy (methylprednisolone 62.5 mg, IV). The treatment with steroids lasted for 1 day only, and in the following day, the patient was switched to prednisone (20 mg/day orally) for only 1 additional day. White blood cell count increased on day 1, 2 and 3 after admission, along development of hyperuricemia, hyperphosphatemia, hyperkalemia, acute renal failure and elevated troponin levels. Hemodiafiltration/hemodialysis was initiated, and the patient was discharged after serum concentrations of these electrolytes and kidney function were restored. One month after discharge, the patient denied any malaise and was at stable condition. CONCLUSIONS Herein, we present a case of a patient with stable chronic lymphocytic leukemia, who developed spontaneous tumor lysis syndrome after short low dose of steroid therapy. This case highlights the importance of including spontaneous tumor lysis syndrome in the differential diagnosis of any acute renal failure in the constellation of any malignancy.