Cases Of End-stage Kidney Disease Research Articles

Assessment of renal response in Tunisian patients with proliferative lupus nephritis under three different induction immunosuppressive agents: A prognostic retrospective study.

The aim of our study was to evaluate the renal response (RR) of three immunosuppressive protocols in the induction treatment of proliferative lupus nephritis (PLN) in a Tunisian population. We performed a retrospective prognostic cohort study in the Internal Medicine Department of the Habib Thameur University Hospital in Tunis from January 2000 to December 2023, and included kidney biopsy proven proliferative lupus nephritis patients. Three induction treatments were compared: High CYP regimen: glucocorticoids (GC) + IV cyclophosphamide (CYP) in monthly pulses of 0.7g/m2 for 6 months; Low CYP regimen: GC + IV CYP in biweekly pulses of 500mg for 3 months; and MMF regimen: GC + oral MMF 1.5g twice daily for 6 months. The primary endpoint was the incidence of RR (complete and partial remission) at one year post-diagnosis. The additional outcomes were end-stage kidney disease (ESKD), severe adverse events (AEs) and death. Our study included 78 PLN patients (High CYP: 17, Low CYP: 40, MMF: 21). The study found that 94.1% of patients receiving High CYP achieved the primary endpoint, RR, compared to 67.5% of those receiving Low CYP and 61.9% in the MMF group. For the additional outcomes, there were 3 cases of ESKD, all in the Low CYP group, 5 cases of death (4 in the Low CYP group and 1 in the MMF group), and 20 cases of severe AEs, all of which were severe infections (5 in the High CYP group, 12 in the Low CYP group, and 3 in the MMF group). Multivariate analysis showed that the High CYP regimen was more associated with RR than the MMF regimen, with an adjusted OR of 9.846 (95% CI: 1.087-98.210); p = 0.042. Multivariate analysis did not show statistically significant differences between the High CYP regimen and the Low CYP regimen in terms of RR. As an induction treatment for PLN, the High CYP regimen was strongly associated with a higher rate of RR than the MMF regimen. There were no statistically significant differences between the High CYP regimen and the Low CYP regimen in terms of RR.

DIABETES MANAGEMENT IN CHRONIC KIDNEY DISEASE: A COMPREHENSIVE SYSTEMATIC REVIEW

Background: The increase in type 2 diabetes has positioned it as the leading cause of chronic kidney disease (CKD) and is responsible for approximately half of all cases of end-stage kidney disease (ESKD) worldwide. Managing CKD in diabetic patients entails addressing its complications and minimizing the risk of other associated conditions, such as cardiovascular disease. This study aims to serve a comprehensive systematic review on diabetes management in CKD patients in literatures of the last 10 years. Methods: The systematic review followed PRISMA 2020 standards and examined full-text English literature published between 2014 and 2024. This review excluded editorials, review papers from the same journal, and submissions without a DOI. Literature was sourced from online platforms such as PubMed, SagePub, SpringerLink, and Google Scholar. Result: A total of 43,740 articles were retrieved from online databases (PubMed, SagePub, SpringerLink and Google Scholar). After three rounds of screening, four articles directly relevant to the systematic review were selected for full-text reading and analysis. Conclusion: Chronic kidney disease (CKD) is a common and serious complication in individuals with diabetes. Management involves controlling hypertension and hyperglycemia, along with using ACE inhibitors like finerenone and SGLT2 inhibitors such as dapagliflozin, sotagliflozin, and bexagliflozin.

Reported cases of end-stage kidney disease—United States, 2000–2019

This article describes trends in end-stage kidney disease in the US between 2000 and 2019, when a 42% increase in incident cases and a 119% increase in prevalent cases of end-stage kidney disease were observed. Hypertension and diabetes mellitus were the primary causes of both incident and prevalent cases of end-stage kidney disease. These trends suggest there will be an ongoing increase in the demand for organ transplantation, a potential negative impact on future organ supply, and underscore the need for increased access to kidney transplantation nationally.

The Canadian Glomerulonephritis Registry (CGNR) and Translational Research Initiative: Rationale and Clinical Research Protocol.

Background:Glomerulonephritis (GN) is a leading cause of kidney failure and accounts for 20% of incident cases of end-stage kidney disease (ESKD) in Canada annually. Reversal of kidney injury and prevention of progression to kidney failure is possible; however, limited knowledge of underlying disease mechanisms and lack of noninvasive biomarkers and therapeutic targets are major barriers to successful therapeutic intervention. Multicenter approaches that link longitudinal clinical and outcomes data with serial biologic specimen collection would help bridge this gap.Objective:To establish a national, patient-centered, multidimensional web-based clinical database and federated virtual biobank to conduct human-based molecular and clinical research in GN in Canada.Design:Multicenter, prospective observational registry, starting in 2019.Setting:Nine participating Canadian tertiary care centers.Patients:Adult patients with a histopathologic pattern of injury consistent with IgA nephropathy, focal and segmental glomerulosclerosis, minimal change disease, membranous nephropathy, C3 glomerulopathy, and membranoproliferative GN recruited within 24 months of biopsy.Measurements:Initial visits include detailed clinical, histopathological, and laboratory data collection, blood, urine, and tonsil swab biospecimen collection, and a self-administered quality of life questionnaire. Follow-up clinical and laboratory data collection, biospecimen collection, and questionnaires are obtained every 6 months thereafter.Methods:Patients receive care as defined by their physician, with study visits scheduled every 6 months. Patients are followed until death, dialysis, transplantation, or withdrawal from the study. Key outcomes include a composite of ESKD or a 40% decline in estimated glomerular filtration rate (eGFR) at 2 years, rate of kidney function decline, and remission of proteinuria. Clinical and molecular phenotypical data will be analyzed by GN subtype to identify disease predictors and discover therapeutic targets.Limitations:Given the relative rarity of individual glomerular diseases, one of the major challenges is patient recruitment. Initial registry studies may be underpowered to detect small differences in clinically meaningful outcomes such as ESKD or death due to small sample sizes and short duration of follow-up in the initial 2-year phase of the study.Conclusions:The Canadian Glomerulonephritis Registry (CGNR) supports national collaborative efforts to study glomerular disease patients and their outcomes.Trial registration:NCT03460054.

Outcomes of Kidney Donors With Impaired Fasting Glucose.

Many kidney donor candidates with impaired fasting glucose (IFG) and all candidates with diabetes are currently excluded from kidney donation, fearing the development of an accelerated course of diabetic kidney disease in the remaining kidney. We studied mortality, proteinuria, and end-stage kidney disease (ESKD) in 8280 donors who donated between 1963 and 2007 according to donation fasting plasma glucose (FPG): <100 mg/dL (n = 6204), 100-125 mg/dL (n = 1826), and ≥126 mg/dL (n = 250). Donors with IFG and those with FPG ≥126 mg/dL were older, less likely to be non-Hispanic White, had a higher body mass index, and were more likely to be related to their recipient. After 15.7 ± 10.5 y from donation to study close, 4.4% died, 29.4% developed hypertension, 13.8% developed proteinuria, and 41 (0.5%) developed ESKD. In both the logistic and Cox models, IFG was associated with a higher diabetes risk (adjusted hazard ratio [aHR], 1.65; 95% confidence interval [CI], 1.18-2.30) and hypertension (aHR, 1.35; 95% CI, 1.10-1.65; P = 0.003 for both), but not higher risk of proteinuria or ESKD. The multivariable risk of mortality in donors with ≥126 mg/dL was higher than the 2 other groups, but risks of proteinuria, cardiovascular disease, and reduced estimated glomerular filtration rate were similar to those with FPG <126 mg/dL. Three cases of ESKD developed in the 250 donors with FPG ≥126 mg/dL at 18.6 ± 10.3 y after donation (aHR, 5.36; 95% CI, 1.0-27.01; P = 0.04). Donors with IFG and the majority of donors with ≥126 mg/dL do well and perhaps should not be routinely excluded from donation.

Implication of Trends in Timing of Dialysis Initiation for Incidence of End-stage Kidney Disease

In the last 2 decades, there have been notable changes in the level of estimated glomerular filtration rate (eGFR) at which patients initiate long-term dialysis in the US and around the world. How changes over time in the likelihood of dialysis initiation at any given eGFR level in at-risk patients are associated with the population burden of end-stage kidney disease (ESKD) has not been not well defined. To examine temporal trends in long-term dialysis initiation by level of eGFR and to quantify how these patterns are associated with the number of patients with ESKD. Retrospective cohort study analyzing data obtained from a large, integrated health care delivery system in Northern California from 2001 to 2018 in successive 3-year intervals. Included individuals, ranging in number from as few as 983 122 (2001-2003) to as many as 1 844 317 (2016-2018), were adult members with 1 or more outpatient serum creatinine levels determined in the prior year. One-year risk of initiating long-term dialysis stratified by eGFR levels. Multivariable logistic regression was performed to assess temporal trends in each 3-year cohort with adjustment for age, sex, race, and diabetes status. The potential change in dialysis initiation in the final cohort (2016-2018) was estimated using the relative difference between the standardized risks in the initial cohort (2001-2003) and the final cohort. In the initial 3-year cohort, the mean (SD) age was 55.4 (16.3) years, 55.0% were women, and the prevalence of diabetes was 14.9%. These characteristics, as well as the distribution of index eGFR, were stable across the study period. The likelihood of receiving dialysis at eGFR levels of 10 to 24 mL/min/1.73 m2 generally increased over time. For example, the 1-year odds of initiating dialysis increased for every 3-year interval by 5.2% (adjusted odds ratio, 1.052; 95% CI, 1.004-1.102) among adults with an index eGFR of 20 to 24 mL/min/1.73 m2, by 6.6% (adjusted odds ratio, 1.066; 95% CI, 1.007-1.130) among adults with an eGFR of 16 to 17 mL/min/1.73 m2, and by 5.3% (adjusted odds ratio, 1.053; 95% CI, 1.008-1.100) among adults with an eGFR of 10 to 13 mL/min/1.73 m2, adjusting for age, sex, race, and diabetes. The incidence of new cases of ESKD was estimated to have potentially been 16% (95% CI, 13%-18%) lower if there were no changes in system-level practice patterns or other factors besides timing of initiating long-term dialysis from the initial 3-year interval (2001-2003) to the final interval (2016-2018) assessed in this study. The present results underscore the importance the timing of initiating long-term dialysis has on the size of the population of individuals with ESKD.

The Association Between Age of Onset of Type 2 Diabetes and the Long-term Risk of End-Stage Kidney Disease: A National Registry Study.

The long-term risk of end-stage kidney disease (ESKD) in type 2 diabetes is poorly described, as is the effect that younger age of diabetes onset has on this risk. Therefore, we aimed to estimate the effect of age of onset on the cumulative incidence of ESKD from onset of type 2 diabetes. This study included 1,113,201 people with type 2 diabetes registered on the Australian National Diabetes Services Scheme (NDSS) followed from 2002 until 2013. The NDSS was linked to the Australia and New Zealand Dialysis and Transplant Registry and the Australian National Death Index. Between 2002 and 2013, there were 7,592 incident cases of ESKD during 7,839,075 person-years of follow-up. In the first 10-15 years following the onset of diabetes, the incidence of ESKD was highest in those with an older age of onset of diabetes, whereas over longer durations of diabetes, the incidence of ESKD became higher in those with younger-onset diabetes. After 40 years of diabetes, the cumulative incidence of ESKD was 11.8% and 9.3% in those diagnosed with diabetes at ages 10-29 and 30-39 years, respectively. When death from ESKD without renal replacement therapy was included, the incidence of ESKD remained higher in older-onset diabetes for the initial 20 years, with no clear effect of age thereafter. The long-term risk of ESKD in type 2 diabetes is high, which disproportionately affects those with younger onset of diabetes because they are more likely to survive to longer diabetes durations.

Lifetime and age-conditional risk estimates of end-stage kidney disease requiring maintenance dialysis in Japan

BackgroundLifetime risk is an epidemiologic measure that expresses the probability of disease in the remaining lifetime for an index age. It is also an easily understandable statistical measure used to communicate the absolute risk of disease to the lay population. The lifetime risk of end-stage kidney disease (ESKD) has never been reported for the Japanese population. Here, we used data from the Japanese Society of Dialysis Therapy (JSDT) to estimate the lifetime risk of ESKD by sex in Japan.MethodsThe lifetime risk of ESKD was estimated using life-table methods. We defined an incident case of ESKD as a patient with loss of kidney function that resulted in maintenance dialysis therapy. The number of incident cases of ESKD and number of ESKD deaths in 2017 were obtained from data published by the JSDT. The population and total number of deaths in Japan for the same year were obtained from National Vital Statistics. By including all-cause mortality, risks were adjusted for competing causes of death.ResultsThe cumulative incidence of ESKD from birth until age 95 years was 3.14% [95% confidence interval (CI) 3.10–3.18] for men and 1.42% (1.39–1.44) for women. These probabilities illustrate that approximately 1 in 32 men and 1 in 71 women in Japan will develop ESKD that results in maintenance dialysis therapy in their lifetime.ConclusionsConsiderable sex differences were found in the lifetime risk of ESKD in Japan. This easily understandable information could be used to assist in public health education and planning.

Smoking and risk of incident end-stage kidney disease in general population: A Nationwide Population-based Cohort Study from Korea

We analyzed data from the Korean National Health Insurance Service (NHIS) to investigate whether smoking increases the risk of end-stage kidney disease (ESKD). This retrospective nationwide population-based cohort study included the data of 23,232,091 participants who underwent at least one health examination between 2009 and 2012. Smoking status was recorded at baseline. The incidence of ESKD was identified via ICD-10 codes and special medical aid codes from the Korean National Health Insurance Service database till December 2016. A Cox proportional-hazards model with multivariable adjustment was used to evaluate the association between smoking and ESKD incidence. Overall, 24.6% of participants were current smokers; 13.5% and 61.9%, were ex- and non-smokers, respectively. Overall, 45,143 cases of ESKD developed during the follow-up period. Current smokers (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.35–1.43) and ex-smokers (HR, 1.09; 95% CI, 1.06–1.12) demonstrated a significant increase in the adjusted risk of ESKD compared to non-smokers. The risk of ESKD was directly proportional to the smoking duration, number of cigarettes smoked daily, and pack-years. In conclusion, smoking is associated with a greater risk of ESKD in the general Korean population; the risk increases with an increase in the smoking duration, number of cigarettes smoked daily, and pack-years.

Association of Serum Uromodulin With ESKD and Kidney Function Decline in the Elderly: The Cardiovascular Health Study

Uromodulin is released by tubular epithelial cells into the serum and lower levels are associated with more severe interstitial fibrosis and tubular atrophy. Low serum uromodulin (sUMOD) levels are associated with mortality and cardiovascular disease. However, little is known about the association of sUMOD levels with long-term kidney outcomes in older adults, a population with a high prevalence of interstitial fibrosis and tubular atrophy. Case-cohort study and case-control study. Random subcohort (n=933) and additional cases of end-stage kidney disease (ESKD) and kidney function decline (≥30% decline in estimated glomerular filtration rate [eGFR]) during follow-up of the Cardiovascular Health Study (CHS). sUMOD level. ESKD (n=14) from the random subcohort and all additional ESKD cases from outside the random subcohort (n=39) during follow-up (10 years, case-cohort study); kidney function decline of≥30% eGFR at 9 years of follow-up in individuals with repeated eGFR assessments from the random subcohort (n=56) and additional cases (n=123). 224 participants from the random subcohort served as controls (case-control study). Modified multivariable Cox regression for ESKD and multivariable logistic regression for kidney function decline. Both analyses adjusted for demographics, eGFR, urinary albumin-creatinine ratio, and other kidney disease progression risk factors. Mean age of the random subcohort was 78 years, 40% were men, 15% were black. Mean sUMOD level was 127±64ng/mL and eGFR was 63±19mL/min/1.73m2. In multivariable analysis, each 1-SD higher sUMOD level was associated with 63% lower risk for ESKD (HR, 0.37; 95% CI, 0.14-0.95). In demographic-adjusted analyses of kidney function decline, each 1-SD higher sUMOD level was associated with 25% lower odds of kidney function decline (OR, 0.75; 95% CI, 0.60-0.95); after multivariable adjustment, the association was attenuated and no longer significant (OR, 0.88; 95% CI, 0.68-1.14). Possibility of survival bias in the kidney function decline analysis. Higher sUMOD levels may identify elderly persons at reduced risk for ESKD.

Urologic care and progression to end-stage kidney disease: a Chronic Kidney Disease in Children (CKiD) nested case–control study

Children with chronic kidney disease (CKD) risk progressing to end-stage kidney disease (ESKD). The majority of CKD causes in children are related to congenital anomalies of the kidney and urinary tract, which may be treated by urologic care. To examine the association of ESKD with urologic care in children with CKD. This was a nested case-control study within the Chronic Kidney Disease in Children (CKiD) prospective cohort study that included children aged 1-16 years with non-glomerular causes of CKD. The primary exposure was prior urologic referral with or without surgical intervention. Incidence density sampling matched each case of ESKD to up to three controls on duration of time from CKD onset, sex, race, age at baseline visit, and history of low birth weight. Conditional logistic regression analysis was performed to estimate rate ratios (RRs) for the incidence of ESKD. Sixty-six cases of ESKD were matched to 153 controls. Median age at baseline study visit was 12 years; 67% were male, and 7% were black. Median follow-up time from CKD onset was 14.9 years. Seventy percent received urologic care, including 100% of obstructive uropathy and 96% of reflux nephropathy diagnoses. Cases had worse renal function at their baseline visit and were less likely to have received prior urologic care. After adjusting for income, education, and insurance status, urology referral with surgery was associated with 50% lower risk of ESKD (RR 0.50 [95% confidence interval [CI] 0.26-0.997), compared to no prior urologic care (Figure). After excluding obstructive uropathy and reflux nephropathy diagnoses, which were highly correlated with urologic surgery, the association was attenuated (RR 0.72, 95% CI 0.24-2.18). In this study, urologic care was commonly but not uniformly provided to children with non-glomerular causes of CKD. Underlying specific diagnoses play an important role in both the risk of ESKD and potential benefits of urologic surgery. Within the CKiD cohort, children with non-glomerular causes of CKD often received urologic care. Urology referral with surgery was associated with lower risk of ESKD compared to no prior urologic care but depended on specific underlying diagnoses.

Update on Diabetic Nephropathy: Core Curriculum 2018

Diabetic kidney disease and diabetic nephropathy are the leading cause of end-stage kidney disease in the United States and most developed countries. Diabetes accounts for 30% to 50% of the incident cases of end-stage kidney disease in the United States. Although this represents a significant public health concern, it is important to note that only 30% to 40% of patients with diabetes develop diabetic nephropathy. Specific treatment of patients with diabetic nephropathy can be divided into 4 major arenas: cardiovascular risk reduction, glycemic control, blood pressure control, and inhibition of the renin-angiotensin system (RAS). Recommendations for therapy include targeting a hemoglobin A1c concentration< 7% and blood pressure< 140/90mmHg with therapy anchored around the use of a RAS-blocking agent. The single best evidence-based therapy for diabetic nephropathy is therapy with a RAS-blocking medication. This Core Curriculum outlines and discusses in detail the epidemiology, pathophysiology, diagnosis, and management of diabetic nephropathy.

Standardised Outcomes in Nephrology\u2014Polycystic Kidney Disease (SONG-PKD): study protocol for establishing a core outcome set in polycystic kidney disease

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the most common potentially life threatening inherited kidney disease and is responsible for 5–10% of cases of end-stage kidney disease (ESKD). Cystic kidneys may enlarge up to 20 times the weight of a normal kidney due to the growth of renal cysts, and patients with ADPKD have an increased risk of morbidity, premature mortality, and other life-time complications including renal and hepatic cyst and urinary tract infection, intracranial aneurysm, diverticulosis, and kidney pain which impair quality of life. Despite some therapeutic advances and the growing number of clinical trials in ADPKD, the outcomes that are relevant to patients and clinicians, such as symptoms and quality of life, are infrequently and inconsistently reported. This potentially limits the contribution of trials to inform evidence-based decision-making. The Standardised Outcomes in Nephrology—Polycystic Kidney Disease (SONG-PKD) project aims to establish a consensus-based set of core outcomes for trials in PKD (with an initial focus on ADPKD but inclusive of all stages) that patients and health professionals identify as critically important.MethodsThe five phases of SONG-PKD are: a systematic review to identify outcomes that have been reported in existing PKD trials; focus groups with nominal group technique with patients and caregivers to identify, rank, and describe reasons for their choices; qualitative stakeholder interviews with health professionals to elicit individual values and perspectives on outcomes for trials involving patients with PKD; an international three-round Delphi survey with all stakeholder groups (including patients, caregivers, healthcare providers, policy makers, researchers, and industry) to gain consensus on critically important core outcome domains; and a consensus workshop to review and establish a set of core outcome domains and measures for trials in PKD.DiscussionThe SONG-PKD core outcome set is aimed at improving the consistency and completeness of outcome reporting across ADPKD trials, leading to improvements in the reliability and relevance of trial-based evidence to inform decisions about treatment and ultimately improve the care and outcomes for people with ADPKD.

Projecting demands for renal replacement therapy in the Northern Territory: a stochastic Markov model.

Objective The aim of the present study was to evaluate the potential effects of different health intervention strategies on demand for renal replacement therapy (RRT) services in the Northern Territory (NT). Methods A Markov chain simulation model was developed to estimate demand for haemodialysis (HD) and kidney transplantation (Tx) over the next 10 years, based on RRT registry data between 2002 and 2013. Four policy-relevant scenarios were evaluated: (1) increased Tx; (2) increased self-care dialysis; (3) reduced incidence of end-stage kidney disease (ESKD); and (4) reduced mortality. Results There were 957 new cases of ESKD during the study period, with most patients being Indigenous people (85%). The median age was 50 years at onset and 57 years at death, 12 and 13 years younger respectively than Australian medians. The prevalence of RRT increased 5.6% annually, 20% higher than the national rate (4.7%). If current trends continue (baseline scenario), the demand for facility-based HD (FHD) would approach 100000 treatments (95% confidence interval 75000-121000) in 2023, a 5% annual increase. Increasing Tx (0.3%), increasing self-care (5%) and reducing incidence (5%) each attenuate demand for FHD to ~70000 annually by 2023. Conclusions The present study demonstrates the effects of changing service patterns to increase Tx, self-care and prevention, all of which will substantially attenuate the growth in FHD requirements in the NT. What is known about the topic? The burden of ESKD is projected to increase in the NT, with demand for FHD doubling every 15 years. Little is known about the potential effect of changes in health policy and clinical practice on demand. What does this paper add? This study assessed the usefulness of a stochastic Markov model to evaluate the effects of potential policy changes on FHD demand. What are the implications for practitioners? The scenarios simulated by the stochastic Markov models suggest that changes in current ESKD management practices would have a large effect on future demand for FHD.

Extrapulmonary tuberculosis presented as fever of unknown origin in two patients with endstage kidney disease not on dialysis: usefulness of 18-FDG-PET/CT in the diagnostic localization of fever of unknown origin.

Tuberculosis is one of the common causes of fever of unknown origin in patients with chronic kidney disease (CKD). Extrapulmonary tuberculosis is more common in CKD patients, and is, unfortunately, often underdiagnosed despite extensive assessments. Recently, fluorine-18-deoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) has been available in the diagnosis of malignancy, inflammatory and infectious diseases, and has become a useful diagnostic tool. Here, we present two cases of endstage kidney disease who presented with fever of unknown origin at the time of dialysis initiation. In both cases, although interferon-gamma-releasing assay was positive, combined conventional diagnostic modalities such as computed tomography and gallium-citrate scintigraphy failed to detect the sites infected with tuberculosis. By contrast, extrapulmonary lesions were detected by FDG-PET/CT and successfully treated with combined anti-tuberculous drugs. Diagnosis of extrapulmonary tuberculosis was confirmed by biopsy of the affected lymph node and lumbar spine, followed by PCR of the biopsied specimen. These cases highlight the importance of considering tuberculosis as one of the differential diagnoses in pre-dialysis CKD patients with persistent fever, and the usefulness of FDG-PET/CT in the detection of infectious sites of extrapulmonary tuberculosis.

Enteric hyperoxaluria: an important cause of end-stage kidney disease.

Hyperoxaluria is a frequent complication of inflammatory bowel diseases, ileal resection and Roux-en-Y gastric bypass and is well-known to cause nephrolithiasis and nephrocalcinosis. The associated prevalence of chronic kidney disease and end-stage kidney disease (ESKD) is less clear but may be more consequential than recognized. In this review, we highlight three cases of ESKD due to enteric hyperoxaluria following small bowel resections. We review current information on the pathophysiology, complications and treatment of this complex disease.

Diabetic kidney disease in Australia: current burden and future projections.

Diabetes mellitus is now the most common cause of new cases of end-stage kidney disease treated with kidney replacement therapy in Australia. In addition to the approximately 5000 Australians receiving maintenance dialysis or living with a kidney transplant as a consequence of diabetes, many die from untreated end-stage kidney disease due to diabetes (DM-ESKD) each year. For every Australian receiving renal replacement therapy due to diabetes, at least 50 others have earlier stages of diabetic kidney disease (DKD). Based on projected increases in type 2 diabetes prevalence, the size of this underlying population with DKD will potentially exceed half a million by 2025. In addition to the risk of developing DM-ESKD, this population is at increased risk of premature cardiovascular morbidity and all-cause mortality. Higher rates of hospitalization, use of specialist services and prescription drugs mean that those with DKD also incur significantly greater health care costs compared with those with diabetes or chronic kidney disease alone. However, in contrast to the increasing prevalence of diabetes and early stages of DKD, recent trends in the incidence of DM-ESKD suggest that better management in the earlier stages of DKD has been successful in slowing rates of disease progression. Simultaneous improvements in use of renin-angiotensin inhibitors and improved glycaemic and blood pressure control are likely to be largely responsible for this trend. Primary prevention, maximizing early detection of DKD and optimal management of diabetes and kidney disease hold great potential to attenuate the future health burden attributable to DKD in Australia.

Diabetic Nephropathy: Do Cannabinoids Contribute?

The current standard of care for diabetic nephropathy is optimization of glycemic control and blood pressure together with the use of renin-angiotensin system inhibitors, which confer benefit over and above their antihypertensive actions. The effectiveness of these treatments has contributed to the lower age-adjusted diabetes-related incidence of end-stage renal disease in the last 10–15 yr (1). However, diabetic nephropathy remains the commonest cause of end-stage renal disease in many Western countries including the United States, and its incidence is also increasing in the developing world. This is due to a combination of the dramatically increasing worldwide prevalence of diabetes and the fact that the above treatments often delay rather than prevent progression of nephropathy. In 2009, 44% of new cases of end-stage kidney disease in the United States were attributable to diabetes (2), whereas the number of new cases of diabetes-related endstage kidney disease in Australia increased by two thirds in those aged over 55 yr from 2000–2007 (3), which is largely attributable to patients with type 2 diabetes. These observations underlie the need for new treatment modalities, and indeed, many diverse options are being pursued (4). In this context, the study by Nam et al. (5) in this issue explores the potential role of cannabinoid receptor 1 blockade in ameliorating nephropathy in a mouse model of type 2 diabetes. Endocannabinoids are arachidonic acid derivatives that regulate energy metabolism (6). They are endogenous ligands for two main receptors, the cannabinoid receptor 1 (CB1) and CB2. The highest concentrations of CB1 receptor are found in the central nervous system where they control feeding behavior and energy expenditure (6, 7). However, CB1 receptors are also expressed in peripheral tissues, including adipose tissue, skeletal muscle, liver, and pancreas, and some of their effects on glucose and lipid metabolism are mediated peripherally (6, 7). Increased activation of the CB1 system is associated with obesity, and there has been intense interest in using CB1 blockade to treat this condition (8). Concomitantly, there is evidence that these agents improve metabolic outcomes such as insulin resistance, glucose intolerance, and dyslipidemia, although the exact mechanisms remain controversial (9). After a series of successful clinical trials, the CB1 antagonist rimonabant (also known as SR141716) was marketed in Europe as an antiobesity agent; however, it was withdrawn shortly thereafter because of psychiatric side effects including anxiety, depression, and suicidal ideation, and it was never approved by the U.S. Food and Drug Administration. This agent acts centrally as well as peripherally, and there is renewed interest in the potential efficacy of CB1 blockers that do not enter the central nervous system and are therefore less likely to have these side effects (8). CB1 receptors have also been identified in kidney cells including podocytes and proximal tubule cells. CB1 receptor blockade ameliorated the development of renal disease in obese Zucker rats and after cisplatin treatment in mice (10). Of particular relevance to the current paper (5), CB1 receptor expression was increased in podocytes of streptozotocin-treated mice, a model of type 1 diabetes (11). Blockade of CB1 using AM251, an inhibitor structurally similar to SR141716, had no effect on glycemia or blood pressure but reduced albuminuria and preserved levels of slit diaphragm proteins in podocytes. In contrast, fibrogenesis and glomerular hypertrophy were not affected by this inhibitor. The current paper (5) studied the effects of SR141716 in db/db mice, a model of type 2 diabetes. SR141716 im-

Pathogenesis and therapy of focal segmental glomerulosclerosis: an update.

Focal and segmental glomerulosclerosis (FSGS) is an important cause of steroid-resistant nephrotic syndrome in adults and children. It is responsible for 5-20% of all cases of end-stage kidney disease (ESKD) in the United States. The pathogenesis of FSGS has not been fully elucidated; however, data from molecular studies of familial cases in the last two decades suggest that FSGS is a defect of the podocyte. The therapeutic agents available for treatment of FSGS are not very effective and only a small percentage of affected individuals will achieve complete remission. Recent data from molecular biology and molecular genetics has provided insight into the mechanisms of action of old agents and also identification of other novel therapeutic targets. This review focuses on recent advances in the molecular pathogenesis of FSGS and currently available therapeutic agents as well as potential novel therapies.

Current structure and organization for renal patient assistance in Italy

Given the public health challenge and burden of chronic kidney disease, the Italian Society of Nephrology (SIN) has compiled a national census of Renal Units (RU) existing in the twenty Italian regions related to the year 2004. An on-line questionnaire including 158 items explored structural and human resources, organization aspects, activities and epidemiological data in SIN, 2004. The census identified 363 public RU, 303 satellite Dialysis Centres (DC) and 295 private DC totalling 961 DC [16.4 per million population (pmp)]. The inpatient renal beds were 2742 (47 pmp). Renal and dialysis activity was performed by 3728 physicians (64 pmp), of whom 2964 (80%) were nephrologists. There was no permanent medical assistance in 41% of satellite DC. There were 1802 renal admissions pmp and 99 renal biopsies pmp. The management of acute renal failure (13 456 cases; 230 pmp) represented a relevant proportion of the activities conducted in public RU. In 2004 there were 9858 new cases of end-stage kidney disease requiring renal replacement therapy (RRT) (169 pmp). On 31 December 2004, 60 058 patients were on RRT (1027 pmp), 43 293 of which (740 pmp) were on dialysis and 16 765 (287 pmp) with renal graft. This census of the Italian RU and DC in 2004 provides decision makers and healthcare stakeholders with detailed data for benchmarking and has financial implications for the public health system. Similar analyses may be conducted in other countries permitting standardization of medical and cost-related aspects of renal care.