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CAKUT stands for Congenital Anomalies of the Kidney and Urinary Tract, and the acronym first appeared in a review article published in 1998. Since then, CAKUT has become a familiar term encountered in the medical literature, especially in nephrology journals. I reason that the term CAKUT was conceived as not a simple description of various diseases, but more as shorthand for a bold conceptual package that linked the occurrence of diverse types of anatomical malformations with insights from genetic and developmental biology research. Moreover, the angiotensin II receptor type 2 was seen as a paradigmatic molecule in the pathobiology of CAKUT. I contend that the acronym, while appearing as an intellectually good idea at the time it was conceived, has outlived its usefulness. To reach these conclusions, I focus on the complex of research observations that led to the theory behind CAKUT, and then question whether these scientific foundations still stand firm. In addition, it is noted that not all clinicians have adopted the acronym, and I speculate why this is the case. I proceed to demonstrate that there is an incompatibility between the semantic meaning of CAKUT and the diseases for which the term was originally conceived. Instead, I suggest the acronym UTM, standing for Urinary Tract Malformation, is a simpler and less ambiguous one to use. Finally, I contend that the continued use of the acronym is a regressive step for the disciplines of nephrology and urology, taking us back two centuries when all kidney diseases were simply called Bright's disease. [ABSTRACT FROM AUTHOR]

In July of 1881, President James A. Garfield was shot in the back at the Sixth Street Train Station in Washington, D.C. Garfield died after an extended illness and Chester A. Arthur assumed the presidency on September 20, 1881. He served the remaining three and a half years but was ill for most of his term. Arthur died of the complications of Bright's disease less than two years after leaving office. In the 1880s, Bright's disease was the syndrome that described renal failure associated with proteinuria, but the etiology of Arthur's kidney failure has never been determined. Arthur is one of our least understood Presidents, owing to his brief tenure in office, his death shortly after leaving office, and the fact that he burned all his personal papers just prior to his death. This manuscript will explore the medical history of Chester A. Arthur, including his presumed diagnosis of malaria, his symptoms during his declining health, and will define the differential diagnosis of the causes of his renal failure that culminated in his death in November of 1886.

Crescentic glomerulonephritis (Crgn) is a complex disorder where macrophage activity and infiltration are significant effector causes. In previous linkage studies using the uniquely susceptible Wistar Kyoto (WKY) rat strain, we have identified multiple crescentic glomerulonephritis QTL (Crgn) and positionally cloned genes underlying Crgn1 and Crgn2, which accounted for 40% of total variance in glomerular inflammation. Here, we have generated a backcross (BC) population (n = 166) where Crgn1 and Crgn2 were genetically fixed and found significant linkage to glomerular crescents on chromosome 2 (Crgn8, LOD = 3.8). Fine mapping analysis by integration with genome-wide expression QTLs (eQTLs) from the same BC population identified ceruloplasmin (Cp) as a positional eQTL in macrophages but not in serum. Liquid chromatography-tandem mass spectrometry confirmed Cp as a protein QTL in rat macrophages. WKY macrophages overexpress Cp and its downregulation by RNA interference decreases markers of glomerular proinflammatory macrophage activation. Similarly, short incubation with Cp results in a strain-dependent macrophage polarization in the rat. These results suggest that genetically determined Cp levels can alter susceptibility to Crgn through macrophage function and propose a new role for Cp in early macrophage activation. [ABSTRACT FROM AUTHOR]

The last several decades have witnessed the emergence of evidence-based medicine as the dominant paradigm for medical teaching, research and practice. Under an evidence-based approach, populations rather than individuals become the primary focus of investigation. Treatment priorities are largely shaped by the availability, relevance and quality of evidence and study outcomes and results are assumed to have more or less universal significance based on their implications at the population level. However, population-level treatment goals do not always align with what matters the most to individual patients-who may weigh the risks, benefits and harms of recommended treatments quite differently. In this article we describe the rise of evidence-based medicine in historical context. We discuss limitations of this approach for supporting realworld treatment decisions-especially in older adults with confluent comorbidity, functional impairment and/or limited life expectancy-and we describe the emergence of more patientcentered paradigms to address these limitations. We explain how the principles of evidence-based medicine have helped to shape contemporary approaches to defining, classifying and managing patients with chronic kidney disease. We discuss the limitations of this approach and the potential value of a more patient-centered paradigm, with a particular focus on the care of older adults with this condition. We conclude by outlining ways in which the evidence-base might be reconfigured to better support real-world treatment decisions in individual patients and summarize relevant ongoing initiatives. [ABSTRACT FROM AUTHOR]

Aims: To develop and validate a model to simulate progression of diabetic kidney disease (DKD) from early onset until end-stage renal disease (ESRD), and to assess the effect of renin-angiotensin system (RAS) intervention in early, intermediate and advanced stages of DKD. Methods: We used data from the BENEDICT, IRMA-2, RENAAL and IDNT trials that assessed effects of RAS intervention in patients with type 2 diabetes. We built a model with discrete disease stages based on albuminuria and estimated glomerular filtration rate (eGFR). Using survival analyses, we assessed the effect of RAS intervention on delaying ESRD in early [eGFR>60 ml/min/1.73m2 and albumin:creatinine ratio (ACR) <30 mg/g], intermediate (eGFR 30-60 ml/min/1.73m2 or ACR 30-300 mg/g) and advanced (eGFR <30 ml/min/1.73m2 or ACR >300 mg/g) stages of DKD for patients in different age groups. Results: For patients at early, intermediate and advanced stage of disease, whose mean age was 60 years and who received placebo, the median time to ESRD was 21.4, 10.8 and 4.7 years, respectively. RAS intervention delayed the predicted time to ESRD by 4.2, 3.6 and 1.4 years, respectively. The benefit of early RAS intervention was more pronounced in younger patients; for example, for patients with a mean age of 45 years, RAS intervention at early, intermediate or advanced stage delayed ESRD by 5.9, 4.0 and 1.1 years versus placebo. Conclusions: RAS intervention early in the course of proteinuric DKD is more beneficial than late intervention in delaying ESRD. [ABSTRACT FROM AUTHOR]

C3 glomerulonephritis is a clinicopathologic entity defined by the presence of isolated or dominant deposits of C3 on immunofluorescence. To explore the effect of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients in whom a complete registry of treatments was available over a median follow-up of 47 months. Twenty patients had not received immunosuppressive treatments. In the remaining 40 patients, 22 had been treated with corticosteroids plus mycophenolate mofetil while 18 were treated with other immunosuppressive regimens (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of patients developing end-stage renal disease was significantly lower among treated compared with untreated patients (3 vs. 7 patients, respectively). No patient in the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor developed end-stage renal disease, as compared with 7 (significant) and 3 (not significant), respectively, in patients treated with other immunosuppressive regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients achieving clinical remission (86, 50, and 25%) were significantly higher in patients treated with corticosteroids plus mycophenolate mofetil as compared with patients treated with other immunosuppressive regimens and untreated patients, respectively. Thus, immunosuppressive treatments, particularly corticosteroids plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis. [ABSTRACT FROM AUTHOR]

Defects in nephrogenesis can have detrimental effects on cardiovascular and renal health in adult life. This is confirmed by observations in the Munich Wistar Frömter ( MWF) rat that exhibits a congenital nephron deficit and renal failure with age. Here, we performed genome-wide transcriptome analysis in embryonic kidneys to identify candidate genes for the reduced nephron number in MWF. We compared MWF rats at embryonic day (E)15.5 with stage-matched spontaneously hypertensive rats ( SHR) at E16. Microarray analysis revealed 311 transcripts representing 253 known genes with differential expression between MWF and SHR (fold change > +1.5 or < −1.5, respectively). Genes located on rat chromosome ( RNO) 6 were of special interest because RNO6 carries genetic loci previously linked to the nephron deficit and renal damage in MWF. Differentially expressed genes located on RNO6 were further investigated by Real-time PCR including the late-stage of fetal kidney development, i.e. E19.0/E19.5, and week 4 of postnatal life when nephrogenesis is completed. Seven genes including Abcg5, Ab1-233, Efcab11, Fntb, Gpx2, Lrrn3, and Rtn1 were assigned on RNO6 and their differential expression was confirmed. Thus, we identified several genes that may act as crucial players in nephron development and are responsible for the nephron deficit in the MWF model. [ABSTRACT FROM AUTHOR]

Background: Glomerular filtration rate (GFR) is considered the indicator of overall kidney function, and therefore, its assessment has become an important clinical tool in the daily care of chronic glomerulonephritis (CGN) patients. Currently, practical guidelines recommend using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to assess GFR in CKD patients. Methods: A cross-sectional study was performed in CGN patients. Standard GFR was measured using 24-hour urine creatinine clearance. GFR was estimated using the Cockcroft- Gault, Modification of Diet in Renal Disease, CKD-EPI equation based creatinine, cystatin C, and combined creatinine and cystatin C. The performance of GFR estimation equations were examined using bias, precision and accuracy and agreement between standard GFR and estimated GFR by calculating Cohen's k. Results: A total of 125 patients (74 male, 59.2%) with mean age 56.1±18.1 years were included. Mean standard GFR was 51.6±32.2 mL/min per 1.73 m2. A significant correlation was found between standard GFR and all estimated GFRs (r=0.573 to 0.660, P<0.001). CKD-EPI-creatinine-cystatin C equation had the smallest absolute bias and the significantly highest accuracy, although it was not significantly different from CKD-EPI-cystatin C equation (P=0.523). CKD-EPI-creatinine-cystatin C equation had the highest accuracy to classify CKD staging (Cohen's k=0.345), but it underestimated GFR in 32% and overestimated GFR in 18% of the CGN patients. Conclusion: CKD-EPI-creatinine-cystatin C equation estimated GFR with little bias, and the highest accuracy among CGN patients. This equation gave a better estimate of GFR than the equation based on serum creatinine. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) affects 10-13% of the general population and diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). In addition to known demographic, biochemical and lifestyle risk factors, genetics is also contributing to CKD risk. In recent years, genome-wide association studies (GWAS) have provided a hypothesis-free approach to identify common genetic variants that could account for the genetic risk component of common diseases such as CKD. The identification of these variants might reveal the biological processes underlying renal impairment and could aid in improving risk estimates for CKD. This review aims to describe the methods as well as strengths and limitations of GWAS in CKD and to summarize the findings of recent GWAS in DN. Several loci and SNPs have been found to be associated with distinct CKD traits such as eGFR and albuminuria. For diabetic kidney disease, several loci were identified in different populations. Subsequent functional studies provided insights into the mechanism of action of some of these variants, such as UMOD or CERS2. However, overall, the results were ambiguous, and a few of the variants were not consistently replicated. In addition, the slow progression from albuminuria to ESRD could limit the power of longitudinal studies. The typically small effect size associated with genetic variants as well as the small portion of the variability of the phenotype explained by these variants limits the utility of genetic variants in improving risk prediction. Nevertheless, identifying these variants could give a deeper understanding of the molecular pathways underlying CKD, which in turn, could potentially lead to the development of new diagnostic and therapeutic tools. [ABSTRACT FROM AUTHOR]

Over the last decades, post-infectious glomerulonephritis underwent major changes in its epidemiology, pathophysiology, and outcomes. We are reporting a case of IgA-dominant post-infectious glomerulonephritis (IgA-PIGN) presenting as a fatal pulmonary-renal syndrome. An 86-year-old Filipino man presented with worsening dyspnea, hemoptysis, and decreased urine output over 2 weeks. Past medical history is significant for hypertension, chronic kidney disease stage III, and pneumonia 3 weeks prior treated with intravenous cefazolin for methicillinsensitive Staphylococcus aureus bacteremia. Physical examination was remarkable for heart rate of 109/min and respiratory rate of 25/min saturating 99% on 3 liters via nasal cannula. There were bibasilar rales in the lungs and bilateral ankle edema. A chest radiograph showed bibasilar opacifications. Blood work was significant for hemoglobin of 8.3 g/dL and creatinine of 9.2 mg/ dL (baseline of 1.67). TTE showed EF 55%. Urinalysis revealed large blood and red blood cell casts. Kidney ultrasound showed bilateral echogenicity compatible with renal disease. Pulse methylprednisolone therapy and hemodialysis were initiated with patient's condition precluding kidney biopsy. Serology workup for rapidly progressive glomerulonephritis was negative. On day 7, the patient required mechanical ventilation; bronchoscopy showed alveolar hemorrhage and plasmapheresis was initiated. Renal biopsy revealed IgA-PIGN with endocapillary and focal extracapillary proliferative and exudative features. IgA-PIGN occurs in diabetic elderly (mean age of 60 years), 0-16 weeks after an infection mainly by Staphylococcus. However, this nondiabetic patient had normal complement IgA-PIGN with fatal pulmonary-renal syndrome. Understanding the pathogenesis and identifying the nephrotoxic bacteria species and the aberrant IgA molecule will open new insights toward prevention and treatment. [ABSTRACT FROM AUTHOR]

Bartonella henselae ( BH) is the main cause of cat scratch disease ( CSD), which more typically presents as a self-limited localized suppurative lymphadenopathy in immunocompetent individuals. In contrast, immunocompromised patients commonly have systemic disease with life-threatening complications. In addition to the angioproliferative lesions, such as bacillary angiomatosis, an increasing number of immune post-infectious complications are being recognized with BH infections, including glomerulonephritis, vasculitis, hemophagocytic syndrome, and neurological problems. We report the case of a renal transplant recipient who developed CSD in the second year post transplantation. In addition to prolonged fever and generalized lymphadenopathy and splenomegaly requiring differentiation from a post-transplant lymphoproliferative disorder, the course was complicated by the development of dermal leukocytoclastic vasculitis and pauci-immune necrotizing and crescentic glomerulonephritis, which led to failure of the renal graft. Glomerulonephritis as a complication of CSD has never been described in a kidney allograft, to our knowledge. Awareness of the diverse clinical symptoms associated with BH, including granulomatous/suppurative lesions and other less common complications can lead to more rapid and accurate diagnosis. Also, as recommended by the current guidelines, a thorough history of pet ownership should be part of the clinical evaluation before and after transplantation for all transplant recipients. [ABSTRACT FROM AUTHOR]

Aims/Introduction To investigate the prevalence and associated risk factors of microalbuminuria, and to explore the relationship between albuminuria and cardiovascular disease ( CVD). Materials and Methods A nationally representative sample of 38,203 Chinese participants was categorized by different levels of urinary albumin-to-creatinine ratio ( ACR; 0 -10 mg/g, 10 -20 mg/g, 20 -30 mg/g, 30 -300 mg/g). The prevalence of albuminuria was compared by using a single urinary ACR cut-off point and by sex-specific ACR cut-off points. Factors associated with the presence of albuminuria, and the relationship between albuminuria and CVD were analyzed by logistic regression. Results Prevalence of albuminuria as measured by a single ACR cut-point was significantly lower for men compared with women (13.9% vs 19.1% in the normal glucose tolerance group; 20.8% vs 26.8% in the impaired glucose tolerance group, P < 0.01). The prevalence of albuminuria, as measured by sex-specific ACR cut-points, was higher for men than women (31.4% vs 29.6% in the normal glucose tolerance group; 42.2% vs 39.3% in the impaired glucose tolerance group, P < 0.01). The independent risk factors for the presence of albuminuria were aging, female sex, hypertension, hyperglycemia, obesity, dyslipidemia, insulin resistance and metabolic syndrome. The subdivided normal ACR group did not show a linear or statistically significant relationship with CVD after adjusting for conventional CVD risk factors ( P > 0.05). Conclusions The prevalence of albuminuria was high in the general Chinese population. Aging, female sex, hypertension, hyperglycemia, dyslipidemia, insulin resistance, obesity and metabolic syndrome were all independent risk factors for albuminuria. The causal relationship between ACR and CVD might require further follow-up investigation. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is the major cause of end stage renal disease (ESRD). We cannot predict which patient will be affected. ESRD patients suffer an extremely high mortality rate, due to a very high incidence of cardiovascular disease. Several randomized, prospective studies have been conducted to quantify the impact of strict glycemic control on morbidity and mortality, and have consistently demonstrated an association between strict glycemic control and a reduction in ESRD. Within the past 20 years, despite the implementation of treatments that were presumed to be renoprotective, diabetes mellitus has continued to rank as the leading cause of ESRD, which clearly indicates that we are still far from understanding the mechanisms involved in the initiation of ESRD. Progressive albuminuria has been considered as the sine qua non of diabetic nephropathy, but we know now that progression to diabetic nephropathy may well happen in the absence of initial microalbuminuria. The search for new biomarkers of early kidney damage has received increasing interest, since early identification of the pathways leading to kidney damage may allow us to adopt measures to prevent the development of ESRD. Most of these biomarkers are deeply influenced by environment, genetics, sex differences, and so on, making it extremely difficult to identify the ideal biomarker to target. At present, there are no new drugs that come close to providing the solutions we desire for our patients (ie, reducing complications). Even when used in combination with standard care, renal complications are, at best, only modestly reduced, at the considerable expense of additional pill burden and exposure to serious off-target effects. In this review, some of the hypothesized mechanisms of this heterogeneous disease will be considered, with particular attention to the tubule-interstitial compartment. [ABSTRACT FROM AUTHOR]

Background: Diabetic autonomic neuropathy is a serious and common complication of diabetes mellitus and in fact it is one of the most overlooked complications, thus very limited clinical and research data are available on early renal and cardiovascular autonomic complications in type 2 diabetes mellitus. Aims & Objective: To determine the possible association of elevated albumin excretion rate with cardiovascular autonomic activity in type 2 diabetes mellitus. Materials and methods: A cross-sectional study was conducted with one hundred and fifteen patients of type 2 diabetes mellitus. Microalbuminuria was defined as Albumin Excretion Rate (AER) > 30 mg/24 hr in an early morning urine sample. Nine parameters reflecting different aspects of cardiovascular autonomic function were measured and were summarized in a single cardiovascular autonomic function score (CAFS).The association between cardiovascular autonomic dysfunction and microalbuminuria was estimated by multiple linear regressions. Results: Patients with microalbuminuria had low levels of the autonomic function parameters i.e. mean CAFS, indicating impaired autonomic function. This association was consistent with increasing AER, and remained significant after multivariate adjustment for other clinical factors predictive of microalbuminuria. In additional analysis, we examined the autonomic function tests combined on the part of autonomic nervous system they predominantly represent. The results of these alternative combinations were comparable to those of the CAFS score. Conclusion: Cardiovascular autonomic dysfunction was independently associated with microalbuminuria in patients with type 2 diabetes mellitus, and that this association is independent of other previously identified determinants of albuminuria in type 2 diabetes mellitus. Therefore cardiovascular autonomic function tests should be monitored to pay attention to major potential cardiovascular complications even in asymptomatic patients, but especially among those with microalbuminuria. [ABSTRACT FROM AUTHOR]

Introduction. Human paraoxonase 1 (PON1) is an enzyme related with high-density lipoprotein cholesterol. The link between genetic polymorphisms of PON1 and hyperlipidemia and increased lipid oxidation may explain these complications in the course of glomerular diseases. In this study, we aimed to investigate PON1 192 and PON1 55 polymorphisms in patients with primary glomerulonephritis and healthy individuals. Materials and Methods. Eighty-six patients with biopsy-proven primary glomerulonephritis and 50 healthy controls were included in the study. Clinical characteristics, lipid profile, paraoxonase activity, and PON1 genotypes (PON1 192 and PON1 55) of all of the participants were studied. Results. Histopathological diagnoses of the patients were membranoproliferative glomerulonephritis (53.5%), focal segmental glomerulosclerosis (33.7%), and membranous nephropathy (12.8%). The patients had lower PON1 activity levels than the healthy controls. No differences were observed in PON1 192 genotypes between the two groups. However, the controls were more likely to carry PON1 55 LM genotype (odds ratio, 4.10; 95% confidence interval, 1.96 to 8.61; P < .001) and M allele (odds ratio, 3.0; 95% confidence interval, 1.45 to 6.19; P = .003) compared to the patients with primary glomerulonephritis. There was a marked elevation in the frequency of PON1 55 LL genotype in the patients compared to the controls (odds ratio, 0.33; 95% confidence interval, 0.16 to 0.68; P = .003). Conclusions. This preliminary study shows that the LL genotype might be a risk factor for the development of primary glomerulonephritis and the M allele might be a protective factor against its progression. [ABSTRACT FROM AUTHOR]

Introduction. Glomerulonephritis is the third most common cause of end-stage renal disease. Epidemiological data of kidney disease is population-based and has great geographic variability. The aim of this study was to assess the results of all kidney biopsies in a 5-year period in the Guilan province. Materials and Methods. In a retrospective study of 336 kidney biopsies recorded in the Department of Nephrology in Razi Hospital of Rasht, capital city of Guilan province, from August 2001 to September 2006, data consisting of age, gender, indication of kidney biopsy, and histopathological diagnosis were collected and analyzed. Results. A total of 336 kidney biopsies were reviewed (73.8% males; mean age, 40.12 ± 16.78 years). Nephritic syndrome (42.5%) and nephrotic syndrome (38.7%) were the most frequent indications of biopsy. Overall, pathologic examinations were indicative of glomerulonephritis in 272 (81.0%) biopsies and nonglomerular diseases in 64 (19.0%). The most common cause of secondary glomerulonephritis was lupus nephritis (82.6%). Focal and segmental glomerusclerosis (20.5%) was the most common pathologic diagnosis, followed by membranous glomerulonephritis (14.9%), minimal change disease (11.6%), tubulointerstitial nephritis (8.9%), and IgA nephropathy (3.6%). The most common pathologic finding among glomerular diseases was focal segmental glomerusclerosis (25.4%), while tubulointerstitial nephritis (46.9%) was the most common among nonglomerular diseases, followed by diffuse glomerulosclerosis, interstitial fibrosis, and tubular atrophy indicative of end-stage renal disease (23.4%). Conclusions. In our study, FSGS was the most common pathologic finding in kidney biopsies, and the frequency of IgA nephropathy was much lower than that in other studies. [ABSTRACT FROM AUTHOR]

Background: The immunosuppressive mammalian target of rapamycin (mTOR) inhibitors are widely used in solid organ transplantation, but their effect on kidney disease progression is controversial. mTOR has emerged as one of the main pathways regulating cell growth, proliferation, differentiation, migration, and survival. The aim of this study was to analyze the effects of delayed inhibition of mTOR pathway with low dose of everolimus on progression of renal disease and TGFβ expression in the 5/6 nephrectomy model in Wistar rats. Methods: This study evaluated the effects of everolimus (0.3 mg/k/day) introduced 15 days after surgical procedure on renal function, proteinuria, renal histology and mechanisms of fibrosis and proliferation. Results: Everolimus treated group (EveG) showed significantly less proteinuria and albuminuria, less glomerular and tubulointerstitial damage and fibrosis, fibroblast activation cell proliferation, when compared with control group (CG), even though the EveG remained with high blood pressure. Treatment with everolimus also diminished glomerular hypertrophy. Everolimus effectively inhibited the increase of mTOR developed in 5/6 nephrectomy animals, without changes in AKT mRNA or protein abundance, but with an increase in the pAKT/AKT ratio. Associated with this inhibition, everolimus blunted the increased expression of TGFβ observed in the remnant kidney model. Conclusion: Delayed mTOR inhibition with low dose of everolimus significantly prevented progressive renal damage and protected the remnant kidney. mTOR and TGFβ mRNA reduction can partially explain this anti fibrotic effect. mTOR can be a new target to attenuate the progression of chronic kidney disease even in those nephropathies of non-immunologic origin. [ABSTRACT FROM AUTHOR]

Mutations in the key enzyme of sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetyl-mannosamine kinase, result in distal myopathy with rimmed vacuoles (DMRV)/hereditary inclusion body myopathy (HIBM) in humans. Sialic acid is an acidic monosaccharide that modifies non-reducing terminal carbohydrate chains on glycoproteins and glycolipids, and it plays an important role in cellular adhesions and interactions. In this study, we generated mice with a V572L point mutation in the GNE kinase domain. Unexpectedly, these mutant mice had no apparent myopathies or motor dysfunctions. However, they had a short lifespan and exhibited renal impairment with massive albuminuria. Histological analysis showed enlarged glomeruli with mesangial matrix deposition, leading to glomerulosclerosis and abnormal podocyte foot process morphologies in the kidneys. Glycan analysis using several lectins revealed glomerular epithelial cell hyposialylation, particularly the hyposialylation of podocalyxin, which is one of important molecules for the glomerular filtration barrier. Administering Neu5Ac to the mutant mice from embryonic stages significantly suppressed the albuminuria and renal pathology, and partially recovered the glomerular glycoprotein sialylation. These findings suggest that the nephrotic-like syndrome observed in these mutant mice resulted from impaired glomerular filtration due to the hyposialylation of podocyte glycoproteins, including podocalyxin. Furthermore, it was possible to prevent the nephrotic-like disease in these mice by beginning Neu5Ac treatment during gestation. [ABSTRACT FROM AUTHOR]

Background: Environmental factors have been associated with the outbreak of chronic kidney disease (CKD). We evaluated the association of Cadmium (Cd) exposure with the risk of CKD in U.S. adults who participated in the 1999-2006 National Health and Nutrition Examination Surveys (NHANES).Methods: 5426 subjects > or = 20 years were stratified for values of urinary and blood Cd and a multivariate logistic regression was performed to test the association between blood and urinary Cd, CKD and albuminuria (ALB) after adjustment for age, gender, race/ethnicity, body mass index and smoking habits.Results: Subjects with urinary Cd > 1 mcg/g and subjects with blood Cd > 1 mcg/L showed a higher association with ALB (OR 1.63, 95% CI 1.23, 2.16; P = 0.001). Subjects with blood Cd > 1 mcg/L showed a higher association with both CKD (OR 1.48, 95% CI 1.01, 2.17; P = 0.046) and ALB (OR 1.41, 95% CI 1.10, 1.82; P = 0.007). An interaction effect on ALB was found for high levels of urinary and blood Cd (P = 0.014).Conclusions: Moderately high levels of urinary and blood Cd are associated with a higher proportion of CKD and ALB in the United States population. [ABSTRACT FROM AUTHOR]

The article profiles Jay Lynn Torrey, a successful attorney, cattle rancher and Rough Rider who was born in Pittsfield, Illinois on October 16, 1852. A discussion of Torrey's attempts to establish a model farm community in Missouri called Fruitville Farms, and a village called Torreytown in Howell County, Missouri, is presented. Factors which prevented Torrey's creation of Fruitville Farms and Torreytown are examined. Torrey's 1920 death from Bright's disease, which occurred six weeks after his marriage to businesswoman Sarah Frances Reiley, is discussed.

Abstract: Several works in the setting of early experimental diabetic nephropathy using anti-inflammatory drugs, such as mycophenolate mofetil (MMF), have shown that prevention of the development or amelioration of renal injury including proteinuria. The exact mechanisms by which anti-inflammatory drugs lower the albuminuria have no still to clarify well. In this study, diabetes was induced by injection of streptozotocin after uninephrectomy. Rats were randomly divided into three groups: control group, diabetic group and diabetic group treated with MMF. Elevated 24h urinary albumin excretion rate was markedly attenuated by MMF treatment. In diabetic rats receiving no treatment, there were increase in ED-1+ cells in the glomeruli, which were effectively suppressed by MMF treatment. The expression of nephrin and podocin protein was reduced in the glomeruli from diabetic rats, and MMF treatment significantly increased the expression of nephrin and podocin. The expression of IL-1, TNF-α and 3-NT protein in the glomeruli were significantly increased in diabetic rats, which were all significantly inhibited by MMF treatment. Our results show that MMF could decrease urinary albumin excretion, which mechanism may be at least partly correlated with upregulated expression of nephrin and podocin in the glomeruli of diabetic rat. [Copyright &y& Elsevier]

Slightly increased urinary albumin excretion is frequently found in patients with lymphoma and other malignancies but the pathophysiological mechanisms have yet to be clarified. In this study, parameters of renal function in lymphoma patients with microalbuminuria were evaluated. Sixty‐seven patients with histologically proven diffuse large B‐cell lymphoma were included in the study at diagnosis. Urinary albumin excretion was measured by immunoturbidimetry and microalbuminuria was defined as an excretion rate between 20 and 200 µg/min. Glomerular function was further estimated by renal clearance of creatinine and IgG, and the IgG/IgG4 charge selectivity index. Tubular function was evaluated by renal clearance of β 2 ‐microglobulin. The median value of IgG clearance was increased in the microalbuminuric patients (0.22 versus 0.18 µl/min; p = 0.03). The median selectivity index was significantly lower in patients with microalbuminuria (1.0 versus 2.2; p [ABSTRACT FROM AUTHOR]

In this article the authors discuss the role of Bright's disease to former U.S. President Chester Alan Arthur's passage of the Pendleton Act. They state that Arthur, who had Bright's disease, was physically ill during debate and passage of Pendleton Act in November 1882 to January 1883. They mention that his suffering from the ill effects of uremia might be the reason for not opposing the civil service reform. They also say that the Bright's disease contributed to his uncharacteristic actions.

Provides information on kidney health and diseases as featured in a number of clinical studies. Contribution of German Physician Friedrich Theodor von Frerichs to the study of nephrology from patients with Bright's disease; Involvement of chemokine monocyte chemoatractant protein-1 in the initiation and progression of tubulointerstitial damage and glomerular lesions; Possibility for patients with an elevated serum potassium may have pseudohyperkalemia.

The article discusses the readily traced and the not so easily identifiable medical eponyms as of 2016. Topics covered include Bright's Disease that derives from physician Richard Bright who described the renal disorder in 1836, and the Brownian motion first noticed by botanist Robert Brown in 1827. Also noted is the Baker's cyst disorder named for surgeon William Morrant Baker that is totally unrelated to the food industry.

Background: Paraneoplastic glomerulonephritis is rare in haematological malignancies and tends to manifest as minimal change disease, membranous glomerulonephritis or membranoproliferative glomerulonephritis. We present the first report of immunoglobulin A nephropathy and associated focal segmental glomerulosclerosis in a patient with asymptomatic low grade B-cell lymphoma.Case Presentation: A 53 year old gentleman presented with nephrotic range proteinuria (urine protein creatinine ratio of 662 mg/mmol) on a background of type 2 diabetes mellitus (glycosylated haemoglobin: < 6%), hypertension, obesity (body mass index: 47.6 kg/m2) and degenerative spine disease. Bone marrow biopsy diagnosed a low grade B-cell lymphoma and renal biopsy was consistent with immunoglobulin A nephropathy. Lymphoma treatment with six cycles of cyclophosphamide/ rituximab/ prednisolone led to normalisation of urinary protein excretion (urine protein creatinine ratio: 14 mg/mmol at 26 months post-chemotherapy).Conclusion: Paraneoplastic immunoglobulin A nephropathy can occur with a broad range of haematological malignancies regardless of stage. This case illustrates the importance of meticulous haematological system work-up for patients presenting with immunoglobulin A nephropathy. Recognition of paraneoplastic immunoglobulin A nephropathy and early diagnosis of associated malignancy can be life-saving. [ABSTRACT FROM AUTHOR]

In July of 1881, President James A. Garfield was shot in the back at the Sixth Street Train Station in Washington, D.C. Garfield died after an extended illness and Chester A. Arthur assumed the presidency on September 20, 1881. He served the remaining three and a half years but was ill for most of his term. Arthur died of the complications of Bright's disease less than two years after leaving office. In the 1880s, Bright's disease was the syndrome that described renal failure associated with proteinuria, but the etiology of Arthur's kidney failure has never been determined. Arthur is one of our least understood Presidents, owing to his brief tenure in office, his death shortly after leaving office, and the fact that he burned all his personal papers just prior to his death. This manuscript will explore the medical history of Chester A. Arthur, including his presumed diagnosis of malaria, his symptoms during his declining health, and will define the differential diagnosis of the causes of his renal failure that culminated in his death in November of 1886.

The article discusses the opinions of medical experts on Alzheimer's disease (AD) therapies after a study by professor R.S. Doody and colleagues related to the drug &#736-secretase inhibitor semagacestat's adverse effects on AD patients. According to professor Christian Haass, Amyloid-lowering therapies are effective as a mutation preventing &#946-secretase cleavage protects from AD and dementia. Also professor Thomas Finucane believes that AD leads to the occurrence of Bright's disease.

We encountered an adult patient with rheumatoid arthritis who developed acute interstitial nephritis associated with an anti-tumor necrosis factor alpha agent, etanercept. [ABSTRACT FROM AUTHOR]

Discusses the prevalence of obesity among patients with chronic kidney disease (CKD) in the U.S. Overview of protein energy malnutrition as the main nutritional concern in the CKD population; Essential components of a weight loss diet program for CKD patients; Strategies to address the epidemic of obesity.

The article reports on the case of an old man who have high blood pressure and was diagnosed with chronic Bright's disease.

Background: Microalbuminuria (MA) is associated with increased risk of cardiovascular and possibly chronic kidney disease (CKD). Obesity has been linked to MA, though the prevalence of MA in overweight groups is not well documented. This population study with an overrepresentation of individuals with BMI >25 (calculated as kg/m2) investigates the prevalence of MA in different BMI categories, and the relationship between MA and BMI. Methods: Data from two cross-sectional epidemiological studies in the City of Sheffield were combined to produce a cohort of non-diabetic, non-CKD subjects over the age of 18. The first study, Kidney Evaluation and Awareness Programme in Sheffield (KEAPS), is a general population screening programme, whilst Kidney Evaluation in Overweight Population in Sheffield (KEOPS) is a screening programme specifically for individuals with BMI >25. Results: The combined database had 1,179 subjects eligible for analysis after applying exclusion criteria. The prevalence of MA in subjects with BMI <25 was 3.1% compared to 12.1% in those with BMI 25–30 and 27.2% in obese subjects with BMI >30 (p < 0.001). The prevalence of MA increased exponentially with the BMI category. BMI is a predictor of MA in logistic regression analyses in the population as a whole, males, females, younger and older age categories, and higher BMI groups (above median and upper tertile). The effect of BMI persists after adjusting for confounding variables. The relative risk for having urine albumin concentration >20 mg/l is 8.0 (95% CI 3.8–16.8, p < 0.0001) if BMI is above the 80th percentile (BMI >27.2). Conclusion: The prevalence of MA increases with increasing BMI in the population of Sheffield. The risk of having MA increases exponentially with BMI. The significance of the high prevalence of MA in overweight and obese individuals should be investigated longitudinally. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Albuminuria predicting outcome in diabetes: Incidence of microalbuminuria in Asia–Pacific Rim. Microalbuminuria is not an unusual finding in the general population, even in individuals without diabetes, hypertension, or cardiovascular risk factors. Prevalence studies in the United States, such as NHANES III, reported an overall incidence of microalbuminuria in 22,244 patients, with and without diabetes, of 7.8%. In those individuals with diabetes, the prevalence was 28.8%. Even in patients without diabetes, cardiovascular disease, or abnormal serum creatinine levels, the prevalence of microalbuminuria was still 5.1%. Similarly, a large Dutch study of 41,000 participants demonstrated a 7% incidence of microalbuminuria. In those individuals with diabetes, the microalbuminuria rate was 16%. Thus, in both the United States and Europe, prevalence studies indicate that microalbuminuria is not uncommon. In southeast Asia and the western Pacific, the incidence of type 2 diabetes is rapidly escalating. It is expected that by 2025 the major prevalence of type 2 diabetes in the world will not be in North America or Europe but in Asia–Pacific Rim. Consequently, there is great interest in evaluating the incidence of microalbuminuria in this region. In the Microalbuminuria Prevalence Study (MAPS) the prevalence of macroalbuminuria was noted to be 18.8% and microalbuminuria 39.8% in a total of 6800 hypertensive diabetic adult patients from 10 Asian countries. Thus, there is important evidence that the substantial prevalence of microalbuminuria and macroalbuminuria in the Pacific region indicates an impending pandemic of diabetic cardiovascular and renal disease. [ABSTRACT FROM AUTHOR]

Albuminuria: Marker or target in indigenous populations. Background Australian Aborigines in remote areas are experiencing an epidemic of renal disease, type 2 diabetes, hypertension, and cardiovascular disease. Adult deaths are increased 3- to 6-fold, and renal failure more than 20-fold. Renal disease is marked by albuminuria. We describe its distributions and correlations in two remote communities in the Northern Territory. Methods Observations in Community 1 included a screen of 939 adult participants (18+ years, 90% recruitment), a treatment program, and 8 to 11 years of follow-up. In Community 2, a screen of 259 people, or 60% of adults, included HbA1c, homocysteine, C-reactive protein (CRP), CMV serology, and carotid intimal media thickness (CIMT). Albumin/creatinine ratio (ACR) was measured by immunoassay in g/mol on random urine, with microalbuminuria defined as 3.4 to 33, and overt albuminuria as ACR 34+. Results Dipstick urine protein trace + correctly classified 76% of people with ACR 3.4+, and dipstick protein 1+ correctly classified 82% of people with ACR 34+. ACR was stable to glucose loading and water diuresis in subsets of people in Community 1. ACR levels rose steeply with age. Rates of micro- and overt albuminuria in Community 1 were 28% and 21%, and in Community B were 31% and 13%. ACR correlated inversely with estimated glomerular filtration rate (GFR). ACR also correlated directly with weight, blood pressure, cholesterol, triglycerides, random glucose, HbA1c, homocysteine, and GGT levels, and inversely with HDL cholesterol. ACR correlated with skin sores, scabies, high titer antibodies to Helicobacter pylori , high-titer CMV antibodies, with CRP over a greatly elevated range and, inversely, with birth weight. Finally, ACR correlated with CIMT. Baseline ACR predicted loss of GFR over time. ACR 3.4+ predicted all-cause and cardiovascular hospitalization, while ACR 34+ predicted all renal failure developing over 11 years and all-cause natural deaths and cardiovascular disease deaths. ACEi treatment for people with ACR 34+ reduced renal failure and natural deaths, but the hierarchical effect of higher ACRs within that group for renal and nonrenal deaths was maintained. Conclusion Random urine ACR is a stable and robust marker of renal disease, which is multideterminant. A broad base of shared risk factors probably explains the simultaneous emergence of the excessive renal and nonrenal chronic disease morbidities from which these populations suffer. Thus, albuminuria is a unifying marker for the harmful effects of the spectrum of chronic disease, and perhaps beyond. Dipstick urine protein is a useful surrogate for ACR when resources are constrained and disease burdens high. [ABSTRACT FROM AUTHOR]

Albuminuria as a surrogate marker for drug development: A European Regulatory perspective. Clinical trials with surrogate end points generally require smaller sample sizes and shorter duration than those with clinical outcomes. However, in practice, surrogate end points are likely to result in less comprehensive conclusions than ‘outcome’ end points as they sometimes reflect only partial aspects of complex phenomena. A number of conditions help to establish the validity of a particular variable as predictive of clinical outcome. This article discusses to what extent albuminuria fulfills these requisites in two particular clinical scenarios: prevention of renal deterioration and prevention of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Mechanism of albuminuria associated with cardiovascular disease and kidney disease. The major underlying factors associated with tissue damage and fibrosis in cardiovascular and kidney disease are the up-regulation and action of growth factors such as transforming growth factor-beta (TGF-β) and cytokines produced in response to changes in systemic factors, particularly blood pressure or hyperglycemia. This study identifies the relationship of elevated levels of TGF-β to increased levels of intact albumin in the urine (micro- and macroalbuminuria). This mechanism may be directly linked to the effect of TGF-β on albumin uptake and the lysosomal breakdown of filtered albumin by proximal tubular cells prior to excretion. [ABSTRACT FROM AUTHOR]

Inclusion of albuminuria in hypertension and heart guidelines. The current recommendations by all United States guideline committees, including the American Diabetes Association and the JNC 7, include screening for microalbuminuria in those with diabetes or evidence of kidney disease, but not the general population. Internationally, both the Canadian and European Guidelines have concurred with this approach. This recommendation is due in part to the findings from long-term outcome studies that measurement of microalbuminuria, while a strong predictor of cardiovascular risk, fails to shows change in CV events if reduced. Unfortunately, this conclusion may be wrong because no randomized trial has examined the question of whether a reduction in microalbuminuria does correlate with a reduction in CV events. Thus, we don't know the answer to this question. Additionally, a recent cost-effective analysis was just published, suggesting it is not worth measuring urinary albumin because it is too expensive for the information obtained. Unfortunately, these conclusions were based on the same faulty logic that relates changes in microalbuminuria to cardiovascular events. It is clear that microalbuminuria is a cardiovascular risk factor, acknowledged by both the JNC 7 and the European Guidelines. Moreover, presence of microalbuminuria correlates strongly with elevated levels of C-reactive protein and abnormal vascular responsiveness to vasodilating stimuli. Thus, its presence indicates abnormal responses by vascular tissue, perhaps due to underlying inflammatory responses. Every clinical trial that has assessed changes in albuminuria as a secondary end point with clinical outcomes has shown a strongly positive correlation between reduction in albuminuria and greater protection of a given end organ; this effect is, in part, independent of blood pressure reduction. Thus, what is needed is a clinical trial in people at high cardiovascular risk, such as those in the INVEST or ALLHAT trials where the primary end point is change in albuminuria and its relationship to cardiovascular outcomes. Likewise, a cardiovascular primary end point could relate to the secondary end point of changes in microalbuminuria, and the latter powered appropriately to make stronger statements about albuminuria and cardiovascular outcomes. With this data, guidelines can then make much strong statements about intervention on this marker of risk. [ABSTRACT FROM AUTHOR]

Albuminuria as a predictor of cardiovascular and renal outcomes in people with known atherosclerotic cardiovascular disease. Background Microalbuminuria predicts elevated cardiovascular risk in those with and without diabetes. In diabetes, microalbuminuria also heralds overt diabetic nephropathy. The predictive value of albuminuria below the microalbuminuria cutoff, and the development of overt nephropathy in nondiabetics with microalbuminuria, have not been well studied. We review findings of the HOPE Study. Methods The HOPE Study database includes data on first morning urine albumin/creatinine ratio (ACR) in 9043 participants at baseline, and in 7674 participants at baseline and at last follow-up. Inclusion criteria were known vascular disease or diabetes, plus one other cardiovascular risk facto; exclusion criteria included heart failure or known impaired left ventricular function, dipstick-positive proteinuria (>1+), and serum-creatinine >2.3 mg/dL (200 μmol/L). Microalbuminuria was defined as an ACR ≥ 2 mg/mmol. Results Microalbuminuria at baseline approximately doubled the relative risk (RR) of the primary outcome (myocardial infarction, stroke, or CV death). For every 1 mg/mmol rise of ACR, even below the level of microalbuminuria, the adjusted hazard of the primary outcome increased by about 15%. Baseline microalbuminuria predicted subsequent clinical proteinuria, RR 17.5, similarly in participants without and with diabetes. New microalbuminuria developed in 1542 participants, and clinical proteinuria in 317. Conclusion Albuminuria is a continuous risk factor for CV events even below the level of microalbuminuria. Microalbuminuria predicts clinical proteinuria in nondiabetics. [ABSTRACT FROM AUTHOR]