Risk Factor For Kidney Failure Research Articles

Filter Resin Kation Pelunak Air Sadah Sumur Gali

Water quality which is not met the standard can cause disturbance and health problems. Waterthat contain high hardness can lead to soap wastefulness, forming precipitation and cookwarecrust, and become one of the risk factors for kidney failure. Various ways can be applied to reduce water hardness, one of which is filtration using ion exchange media. The ion exchangemedia used in this study is cation resin. The purpose of this study was to determine the effect ofcation resin thickness variation at filter on the decrease of well water hardness. This researchwas an experiment with pre-test post-test with control group design, and was conducted in January 2018, located in Pereng hamlet of, Bumirejo, Lendah, Kulon Progo Regency. The datawere analysed using one way anova. The average water hardness before processing was 460mg/l, while the mean decrease in the control group was 42,66 mg/l; in P1 group was 197,33 mg/l, in P2 group was 197,33 mg/l, and in P3 group was 197,33 mg/l. The results of data analysisshowed that the thickness variations of cation resin influence the decrease of well water hardness in the control group, and P1, P2, and P3 groups (p-value <0,001). The most effective cation resin thickness is the P3 group, i.e. filter with 11 cm thickness cation resin.

Risk Factors for Prognosis in Patients With Severely Decreased GFR

IntroductionPatients with chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) <30 ml/min per 1.73 m2 (corresponding to CKD stage G4+) comprise a minority of the overall CKD population but have the highest risk for adverse outcomes. Many CKD G4+ patients are older with multiple comorbidities, which may distort associations between risk factors and clinical outcomes.MethodsWe undertook a meta-analysis of risk factors for kidney failure treated with kidney replacement therapy (KRT), cardiovascular disease (CVD) events, and death in participants with CKD G4+ from 28 cohorts (n = 185,024) across the world who were part of the CKD Prognosis Consortium.ResultsIn the fully adjusted meta-analysis, risk factors associated with KRT were time-varying CVD, male sex, black race, diabetes, lower eGFR, and higher albuminuria and systolic blood pressure. Age was associated with a lower risk of KRT (adjusted hazard ratio: 0.74; 95% confidence interval: 0.69–0.80) overall, and also in the subgroup of individuals younger than 65 years. The risk factors for CVD events included male sex, history of CVD, diabetes, lower eGFR, higher albuminuria, and the onset of KRT. Systolic blood pressure showed a U-shaped association with CVD events. Risk factors for mortality were similar to those for CVD events but also included smoking. Most risk factors had qualitatively consistent associations across cohorts.ConclusionTraditional CVD risk factors are of prognostic value in individuals with an eGFR <30 ml/min per 1.73 m2, although the risk estimates vary for kidney and CVD outcomes. These results should encourage interventional studies on correcting risk factors in this high-risk population.

Uric Acid and the Risks of Kidney Failure and Death in Individuals With CKD

Serum uric acid concentrations increase in chronic kidney disease (CKD) and may lead to tubular injury, endothelial dysfunction, oxidative stress, and intrarenal inflammation. Whether uric acid concentrations are associated with kidney failure and death in CKD is unknown. Prospective observational cohort study. 3,885 individuals with CKD stages 2 to 4 enrolled in the Chronic Renal Insufficiency Cohort (CRIC) between June 2003 and September 2008 and followed up through March2013. Baseline uric acid concentrations. Kidney failure (initiation of dialysis therapy or transplantation) and all-cause mortality. During a median follow-up of 7.9 years, 885 participants progressed to kidney failure and 789 participants died. After adjustment for demographic, cardiovascular, and kidney-specific covariates, higher uric acid concentrations were independently associated with risk for kidney failure in participants with estimated glomerular filtration rates (eGFRs)≥ 45mL/min/1.73m2 (adjusted HR per 1-standard deviation greater baseline uric acid, 1.40; 95% CI, 1.12-1.75), but not in those with eGFRs<30mL/min/1.73m2. There was a nominally higher HR in participants with eGFRs of 30 to 44mL/min/1.73m2 (adjusted HR, 1.13; 95% CI, 0.99-1.29),butthis did not reach statistical significance.The relationship between uric acid concentrationand all-cause mortality was J-shaped (P=0.007). Potential residual confounding through unavailable confounders; lack of follow-up measurements to adjust for changes in uric acid concentrations over time. Uric acid concentration is an independent risk factor for kidney failure in earlier stages of CKD and has a J-shaped relationship with all-cause mortality in CKD. Adequately powered randomized placebo-controlled trials in CKD are needed to test whether urate lowering may prove to be an effective approach to prevent complications and progression of CKD.

Incidence of End-Stage Renal Disease Attributed to Diabetes Among Persons with Diagnosed Diabetes - United States and Puerto Rico, 2000-2014.

During 2014, 120,000 persons in the United States and Puerto Rico began treatment for end-stage renal disease (ESRD) (i.e., kidney failure requiring dialysis or transplantation) (1). Among these persons, 44% (approximately 53,000 persons) had diabetes listed as the primary cause of ESRD (ESRD-D) (1). Although the number of persons initiating ESRD-D treatment each year has increased since 1980 (1,2), the ESRD-D incidence rate among persons with diagnosed diabetes has declined since the mid-1990s (2,3). To determine whether ESRD-D incidence has continued to decline in the United States overall and in each state, the District of Columbia (DC), and Puerto Rico, CDC analyzed 2000-2014 data from the U.S. Renal Data System and the Behavioral Risk Factor Surveillance System. During that period, the age-standardized ESRD-D incidence among persons with diagnosed diabetes declined from 260.2 to 173.9 per 100,000 diabetic population (33%), and declined significantly in most states, DC, and Puerto Rico. No state experienced an increase in ESRD-D incidence rates. Continued awareness of risk factors for kidney failure and interventions to improve diabetes care might sustain and improve these trends.

Long term renal survival in patients undergoing T-Cell depleted versus conventional hematopoietic stem cell transplants.

Calcineurin inhibitor-sparing T cell depleted (TCD) hematopoietic stem cell transplants HSCTs are presumed less nephrotoxic than conventional HSCTs. We evaluated incidence and risk factors for kidney failure and chronic kidney disease (CKD) in 231 TCD and 212 conventional HSCT recipients. Kidney failure required a median glomerular filtration rate (GFR) <60 mL/min/1.73 m2 for ≥ 100 days anytime after 180 days post-HSCT. Two year cumulative incidence (CI) of kidney failure was 42% in the conventional vs. 31% in the TCD group (p=0.005). TCD, age, acute kidney injury and number of toxic CNI levels all impacted on kidney failure, which was associated with increased all-cause mortality (hazard ratio 2.86 (95% CI: 1.88–4.36), p <0.001). Renal recovery occurred in 28% of kidney failure patients, while the remaining patients were defined to have chronic kidney disease (CKD). In those with baseline GFR>60 mL/min/1.73 m2 only exposure to nephrotoxic medications was associated with CKD (p=0.033). In the myeloablative conditioning subgroup only total body irradiation was associated with CKD (p=0.013). Of all patients, five (1.13%) required dialysis. These results confirm an impact of TCD on kidney failure but not CKD for which other risk factors such as radiation or nephrotoxic drug exposure may play a role.

Risk Factors for Rapid Kidney Function Decline Among African Americans: The Jackson Heart Study (JHS).

Racial differences in rapid kidney function decline exist, but less is known regarding factors associated with rapid decline among African Americans. Greater understanding of potentially modifiable risk factors for early kidney function loss may help reduce the burden of kidney failure in this high-risk population. Prospective cohort study. 3,653 African American participants enrolled in the Jackson Heart Study (JHS) with kidney function data from 2 of 3 examinations (2000-2004 and 2009-2013). Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine using the CKD-EPI creatinine equation. Demographics, socioeconomic status, lifestyle, and clinical risk factors for kidney failure. Rapid decline was defined as a≥30% decline in eGFR during follow-up. We quantified the association of risk factors with rapid decline in multivariable models. Clinical (systolic blood pressure and albuminuria [albumin-creatinine ratio]) and modifiable risk factors. Mean age was 54±12 (SD) years, 37% were men, average body mass index was 31.8±7.1kg/m(2), 19% had diabetes mellitus (DM), and mean eGFR was 96.0±20mL/min/1.73m(2) with an annual rate of decline of 1.27mL/min/1.73m(2). Those with rapid decline (11.5%) were older, were more likely to be of low/middle income, and had higher systolic blood pressures and greater DM than those with nonrapid decline. Factors associated with≥30% decline were older age (adjusted OR per 10 years older, 1.51; 95% CI, 1.34-1.71), cardiovascular disease (adjusted OR, 1.53; 95% CI, 1.12-2.10), higher systolic blood pressure (adjusted OR per 17mmHg greater, 1.22; 95% CI, 1.06-1.41), DM (adjusted OR, 2.63; 95% CI, 2.02-3.41), smoking (adjusted OR, 1.60; 95% CI, 1.10-2.31), and albumin-creatinine ratio > 30mg/g (adjusted OR, 1.55; 95% CI, 1.08-1.21). Conversely, results did not support associations of waist circumference, C-reactive protein level, and physical activity with rapid decline. No midstudy creatinine measurement at examination 2 (2005-2008). Rapid decline heterogeneity exists among African Americans in JHS. Interventions targeting potentially modifiable factors may help reduce the incidence of kidney failure.

Frequency of kidney failure in cardiologic patients: the need to search

Chronic kidney disease is a major health problem since it is associated with a high cardiovascular risk, total morbidity and mortality, increasing prevalence and high cost treatment. To assess the frequency of chronic kidney disease among patients consulting in a cardiology clinic. Cross-sectional assessment of 649 patients attended at a cardiology clinic. Demographic, clinical, electrocardiographic, echocardiographic and laboratory variables were registered. Patients were considered to have a kidney failure when their estimated glomerular filtration rate was < 60 ml/min/1.73 m² according to the Modification of Diet in Renal Disease (MDRD) formula. Kidney failure was considered chronic if this alteration lasted ≥ 3 months and hidden when serum creatinine levels were normal. The frequency of kidney failure was 20.8% (28.4% in patients ≥ 65 years old). The mean age of patients with the disease was 71.5 ± 9.1 years and 52% were women. Eighty seven percent were in stage 3, 10% in stage 4 and 3% in stage 5. Among patients with kidney failure, in 114 (84%) it was chronic and in 28%, hidden. The latter was observed almost exclusively in women with creatinine levels of approximately 1 mg/dl. Hypertension (Odds ratio (OR) 4.2), age (OR 1.1), ventricular ejection fraction (OR 0.97) and low hemoglobin (OR 0.735) were the risk factors for kidney failure detected in the multivariate analysis. The frequency of kidney failure (chronic or hidden) was high in this group of cardiologic patients. Most patients had a mild to moderate failure and the risk factors were hypertension, age, low ventricular ejection fraction and low hemoglobin levels.

The Cath-Assist: A Self-Catheterization Assistive Device1

The Cath-Assist: A Self-Catheterization Assistive Device1

Monitoring Kidney Function in Neuroendocrine Tumor Patients Treated with (90)Y-DOTATOC: Associations with Risk Factors.

Peptide receptor radionuclide therapy (PRRT) is an established treatment for progressive neuroendocrine tumours with nephrotoxicity as the limiting factor. It is therefore important to monitor kidney function changes after PRRT treatment. We aimed to investigate kidney function by different methods and during a 4-hour and a 24-hour amino acid (AA) infusion protocol. We measured the Glomerular Filtration Rate (GFR) in 28 patients before and 3, 6, 12, and 18 months after (90)YDOTATOC therapy. We used standardized (51)Cr-EDTA plasma clearance (Cr-GFR) and estimated GFR (eGFR) by the simplified 4 variable Modification of Diet in Renal Disease based on serum creatinine values. Further, we determined GFR in 15 patients treated with a 4-hour infusion of AA compared to 13 patients with a 24-hour infusion at 3, 6, 12 and 18 months after therapy. Pre-existing risk factors associated with kidney failure were seen in 82% of the patients. We observed a significant reduction in Cr-GFR up to 12 months after PRRT (mean loss 27 ml/min/1.73 m(2) (32%)). The eGFR continuously overestimated the Cr-GFR with a bias of 8%. There was no significant difference between the two AA protocols, however, the 24-hour AA protocol tended to reduce mean Cr-GFR loss 12 months post therapy. Pre-existing risk factors for kidney failure were highly prevalent in this patient cohort, and kidney function after PRRT treatment is best monitored by (51)Cr-EDTA plasma clearance. Further, the use of a 24-hour AA kidney protection protocol seems to reduce the loss of kidney function in these patients.

Nephrocalcinosis is a risk factor for kidney failure in primary hyperoxaluria

Stone formation and nephrocalcinosis are both very common features of primary hyperoxaluria, yet the extent of each disease varies markedly between patients. Here we studied whether kidney damage from nephrocalcinosis and/or stone related events contributed to end stage kidney disease (ESKD). Clinical information was analyzed from 348 patients enrolled in the Rare Kidney Stone Consortium Primary Hyperoxaluria registry and included demographic, laboratory and imaging features. Among all patients there were 277 with type 1, 37 with type 2, and 34 with type 3 primary hyperoxaluria. Overall, 58% passed a stone (mean 0.3/year) and one or more urologic procedures were required by 70% of patients (mean 0.15/year). Nephrocalcinosis was found in 34% of patients, including 41% with type 1 primary hyperoxaluria. High urine oxalate was associated with increased risk for both nephrocalcinosis and stone number, while low urine citrate was a risk factor for stone events and stone number. After adjustment for the type of primary hyperoxaluria, diagnosis by family screening and age at first image, the overall adjusted hazard ratio for ESKD among those with a history of nephrocalcinosis was 1.7 [95% CI 1.0–3.0], while the risk was 4.0 [1.9–8.5] for new onset nephrocalcinosis during follow-up. In contrast, the number of stones and stone events were not significantly associated with ESKD risk. Thus, nephrolithiasis and nephrocalcinosis appear to be pathophysiologically distinct entities. The presence of nephrocalcinosis implies increased risk for ESKD.

Familial Risks of Kidney Failure in Sweden: A Nationwide Family Study

BackgroundThe value of family history as a risk factor for kidney failure has not been determined in a nationwide setting.AimThis nationwide family study aimed to determine familial risks for kidney failure in Sweden.MethodsThe Swedish multi-generation register on 0–78-year-old subjects were linked to the Swedish patient register and the Cause of death register for 1987–2010. Individuals diagnosed with acute kidney failure (n = 10063), chronic kidney failure (n = 18668), or unspecified kidney failure (n = 3731) were included. Kidney failure patients with cystic kidney disease, congenital kidney and urinary tract malformations, urolithiasis, and rare inherited kidney syndromes, and hyperoxaluria were excluded. Standardized incidence ratios (SIRs) were calculated for individuals whose parents/siblings were diagnosed with kidney failure compared to those whose parents or siblings were not.ResultsThe concordant (same disease) familial risks (sibling/parent history) were increased for chronic kidney failure SIR = 2.02 (95% confidence interval, CI 1.90–2.14) but not for acute kidney failure SIR = 1.08 (95% CI 0.94–1.22) and for unspecified kidney failure SIR = 1.25 (95% CI 0.94–1.63). However, the discordant (different disease) familial risk for acute kidney failure SIR = 1.19 (95% CI 1.06–1.32) and unspecified kidney failure SIR = 1.63 (95% CI 1.40–1.90) was significantly increased in individuals with a family history of chronic kidney failure. The familial risk for chronic kidney failure was similar for males SIR = 2.04 (95% CI 1.90–2.20) and females SIR = 1.97 (95% CI 1.78–2.17). Familial risks for chronic kidney failure were highest at age of 10–19 years SIR = 6.33 (95% CI 4.16–9.22).ConclusionsThe present study shows that family history is an important risk factor for chronic kidney failure but to a lower degree for acute kidney failure and unspecified kidney failure.

Estimated glomerular filtration rate and albuminuria

To describe the relationship between estimated glomerular filtration rate (eGFR), albuminuria, and important outcomes for patients with chronic kidney disease (CKD). The first part of the review presents the evidence linking eGFR and albuminuria to important clinical outcomes, and the second part highlights the importance of these risk relationships across multiple subgroups and in clinical risk prediction. Investigators have used data from large population-based cohort studies and conducted collaborative meta-analyses to definitively establish the relationship between eGFR, albuminuria, and adverse clinical outcomes. Recent systematic reviews have also highlighted the importance of these variables in predicting the risk of kidney failure and all-cause mortality. eGFR and albuminuria are important independent risk factors for kidney failure, acute kidney injury, and all-cause or cardiovascular mortality. These relationships are independent of age, sex, race, or ethnicity. eGFR and albuminuria can be combined with other demographic variables to accurately predict the risk of kidney failure and should be measured concurrently to determine diagnosis, staging, and prognosis in patients with CKD.

Depression Doubles Mortality Risk among Transplant Recipients

Renal transplantation is the best available treatment for patients with kidney failure, but recipients have been shown to develop emotional distress and affective disorders, such as anxiety and depression, associated with a compromised quality of life (QoL). Depression is associated with impaired QoL and increased morbidity and mortality in patients with end-stage renal disease (ESRD). Research has confirmed that depression may worsen kidney transplant outcome. Dobbles et al. reported in the American Journal of Kidney Diseases (2008), that depression is considered as a high risk factor for kidney failure, return to dialysis and death among the studied kidney transplant recipients. They found after examining the patients' records, from 1905-2003, that the incidence of depression was about 7% the first year after transplantation, 11% in the second year and 13% in the third year. According to this study, kidney failure occurred in 19% of the patients, 8% died with a functioning kidney and 11% had to return to dialysis therapy. This study concluded that depression may double the risk of adverse outcomes. It is suggested that recipients should be recommended for depression screening that is essential to evaluate and monitor the occurrence of depression and identify high risk recipients after transplant that can be referred for psychological intervention.

N-Palmitoylethanolamide protects the kidney from hypertensive injury in spontaneously hypertensive rats via inhibition of oxidative stress

Hypertension is an important risk factor for kidney failure and renal events in the general population. Palmitoylethanolamide (PEA) is a member of the fatty acid ethanolamine family with profound analgesic and anti-inflammatory effects, resulting from its ability to activate peroxisome proliferator activated receptor (PPAR)α. A role for this nuclear receptor has been addressed in cardiovascular system and PPARα ligands have been shown to protect against inflammatory damage especially resulting from angiotensin II hypertension.In this study, we demonstrated that PEA significantly reduced blood pressure in spontaneously hypertensive rats (SHR) and limited kidney damage secondary to high perfusion pressure. To investigate the mechanisms involved in PEA effect, we found that PEA reduced cytochrome P450 (CYP) hydroxylase CYP4A, epoxygenase CYP2C23 and soluble epoxide hydrolase enzyme expression in the kidney, accompanied by a reduction of 20-hydroxyeicosatetraenoic acid excretion in the urine. Moreover, it markedly reduced kidney oxidative and nitrosative stress accompanied by decreased expression of renal NAD(P)H oxidase and inducible nitric oxide synthase and increased expression of Cu/Zn superoxide dismutase, in the kidney of SHR. Moreover, angiotensin II receptor (AT) evaluation revealed a decrease in AT1 receptor expression and a restoration of AT2 receptor level in the kidney from PEA-treated SHR. Consistently, angiotensin converting enzyme expression was reduced, implying a decrease in angiotensin II synthesis. These results indicate that PEA treatment lowers blood pressure and can protect against hypertensive renal injury by increasing the antioxidant defense and anti-inflammatory response and modulating renin-angiotensin system.

Hypertension: Silent and/or ignored / L’hypertension silencieuse ou ignorée

Ignore this editorial. Hypertension is so banal—it’s really common, easily measured and assessed, the treatment is mostly pharmacologic. . . . Wait a minute! That should be very exciting for pharmacists. Consider these facts: Hypertension is the number 1 leading risk factor for death and disability globally.1 Infectious diseases, poor sanitation and HIV are important, too, but 13% of all deaths (9.4 million annually) and 7% of all disability are caused by increased blood pressure. The World Health Organization (WHO) has declared its World Health Day 2013 theme to be hypertension.2 Indeed, in terms of “doing the most good for the most people,” as a pharmacist, focusing on hypertension might be the most important thing you can do. As you know, when blood pressure increases above 115/70 mmHg, blood vessels are damaged, causing more than half of all strokes and cases of heart disease, as well as being a major risk factor for kidney failure, dementia and other vascular diseases.3 World Health Day in 2013 plans to focus attention on the causes and consequences of hypertension, the need for people to adopt healthy behaviours to prevent hypertension, the need for regular blood pressure checks and the need for governments to create healthy environments to assist in preventing hypertension.2 Canada is well advanced in efforts to prevent and control hypertension compared with many countries. About 1 in 5 adult Canadians have hypertension, while the rate in many countries is over 3 in 10. Canada also has the highest national rate of treatment and control of hypertension,4,5 possibly because it has had strong nongovernmental and governmental partnerships, an extensive interdisciplinary hypertension education program (CHEP) and a well-organized hypertension community, led by Hypertension Canada (www.hypertension.ca).6 Canada also has a recently updated Pan-Canadian Framework to help guide the effort to prevent and control hypertension.7 Further, a national committee of health care and scientific organizations (the Canadian Hypertension Advisory Committee), including the Canadian Pharmacists Association, is helping guide and prioritize actions for prevention and control of hypertension. Look for the updated hypertension guidelines for pharmacists in the next issue of CPJ. By the numbers: #1: Hypertension is the number 1 risk for death and disability around the globe. 1/5 of Canadians have hypertension. 90% of Canadians living an average life span will develop hypertension. 1/3 of Canadians with hypertension are not controlled. 44% of people with diabetes have poor hypertension control. Although much has been accomplished, far too many Canadians remain adversely affected by increased blood pressure. It is estimated that over 90% of Canadians living an average life span will develop hypertension and that close to 7.5 million adult Canadians have hypertension.8,9 Many Canadians are particularly vulnerable, including ethnic minorities and people with low incomes and education. Close to 1 in 3 Canadians have uncontrolled hypertension10 (as do 44% of people with diabetes)11 and lack of awareness of hypertension is common in young adults.10 Cardiovascular risk factors other than blood pressure are largely not well controlled in people with hypertension. And, because much of hypertension is caused by unhealthy diets, the Canadian Hypertension Advisory Committee is focused on advocating for the implementation of healthy food policies7 (see https://www.facebook.com/HypertensionTalk?ref=stream).

Gadolinio y fibrosis sistémica nefrogénica

IntroductionGadolinium is a contrast medium used in MRI. Gadolinium compounds differ in their chemical structure. The administration of these compounds has been associated with the emergence of a rare but serious disease called nephrogenic systemic fibrosis, predominantly characterized by skin involvement. Materials and methodsIn our center we have three MRI scans of 1.5T and 3T MRI and use different gadolinium compounds. ResultsThis article will discuss the guidelines for the administration of the different compounds of gadolinium. It summarizes the precautions and procedures in different situations. All processes that produce a decrease in glomerular filtration rate and affect renal function, are considered risk factors for the development of nephrogenic systemic fibrosis. ConclusionsGadolinium is a contrast medium in MRI that provides much information, but we must be aware of its limitations, especially in relation to the nephrogenic systemic fibrosis.Recommendations on the use of gadolinium. Adults: A questionnaire will be used by the technician or radiologist to assess risk factors for kidney failure, and if possible, the glomerular filtration rate is obtained. Children: Information for nursing mothers and parents on the risk of gadolinium and its accumulation.

Smoking is a risk factor in the progression to kidney failure

To study the role of smoking in renal damage, we measured gender-specific effects, dose-response relationships, and whether cessation reduced the risk of smoking on future kidney failure. During a median follow-up of 10.3 years, 124 of 65,589 participants of the HUNT II study, a Norwegian population, progressed to stage 5 chronic kidney disease. Former- and current-smokers less than 70 years of age at inclusion had significant multi-adjusted hazard ratios of 3.32 and 4.01 for kidney failure compared to those who never smoked. In men, the risk increased with a significantly higher trend for cumulative smoking (pack-years); however, the risk significantly decreased with increased elapsed years since smoking cessation. Although the prevalence of current smoking did not differ between genders, females had smoked less (10.2 compared to 15.8 pack-years) and the number of kidney failure cases was lower in females than in men (46 compared to 78). The effect of smoking on the risk of kidney failure was similar (hazard ratios of 2.94 and 4.30 in current-smoking women and men, respectively), but did not reach statistical significance in women. Thus, in this large population-based sample, we found that smoking is a significant risk factor for future kidney failure. Smoking cessation decreased this risk, at least in men.

Glucarpidase (Carboxypeptidase G2) Intervention in Adult and Elderly Cancer Patients with Renal Dysfunction and Delayed Methotrexate Elimination After High-Dose Methotrexate Therapy

Leucovorin and extracorporeal removal of methotrexate (MTX) have limited efficacy in delayed MTX elimination after high-dose methotrexate (HD-MTX) therapy. Glucarpidase (carboxypeptidase G2) cleaves MTX into nontoxic metabolites, but experience with this enzyme is limited in adult patients. We evaluated the effects of glucarpidase intervention in adult and elderly patients with delayed MTX elimination. Forty-three patients (age, 18-78 years) with MTX serum concentrations (sMTX) of 1-1,187 micromol/l received glucarpidase, leucovorin rescue guided by MTX immunoassay, and standard supportive care. MTX and MTX metabolites were quantified in serum (24 patients) and urine (8 patients) by high-performance liquid chromatography. Contributory risk factors, toxicities, and survival were recorded in all patients. Glucarpidase was well tolerated and resulted in an immediate >97% reduction in sMTX, with a 0.2%-35% urinary recovery of the total MTX dose as inactive MTX metabolites. Forty (93%) of 43 patients had normalization (n = 25) or improvement (n = 15) of their serum creatinine. Frequent grade III-IV MTX toxicities were hematological (60%) and mucositis (35%); only eight (19%) patients developed grade III-IV nephrotoxicity. Ten (23%) of 43 patients experienced fatal complications associated with HD-MTX therapy. Patients with three or more contributory risk factors for delayed MTX elimination had a significantly poorer survival than patients with fewer than three risk factors (hazard ratio, 3.64; confidence interval, 1.14-17.54). Glucarpidase is well tolerated and produces a rapid inactivation of substantial amounts of MTX. However, overall results are still unsatisfactory in adult and elderly patients, suggesting that earlier recognition of delayed MTX elimination and more rapid intervention are needed.

Excess weight as a risk factor for kidney failure

The increasing incidence of end-stage renal disease and the epidemic of obesity are major public health problems. We review recent epidemiological evidence that excess weight is an important risk factor for chronic kidney disease and end-stage renal disease. A cohort study of over 300 000 adults and 8 million years of follow-up determined that elevated BMI was a significant risk factor for end-stage renal disease. This relationship was evident starting at a BMI of 25 kg/m and persisted after adjustment for hypertension and diabetes. A population-based case-control study showed that a BMI of at least 25 kg/m at age 20 was significantly associated with development of advanced chronic kidney disease. This was true even among those without diabetes or hypertension. Excess weight is a common, strong and modifiable risk factor for chronic kidney disease and end-stage renal disease. Even individuals who are not overtly obese are at risk. Excess weight contributes to chronic kidney disease and end-stage renal disease over and above its role in hypertension and diabetes. Weight loss may represent a novel intervention to reduce risk of chronic kidney disease development and progression.

Proteinuria reduction and progression to renal failure in patients with type 2 diabetes mellitus and overt nephropathy

Little is known of the effects of blood pressure reduction by specific classes of antihypertensive drugs on the association between proteinuria reduction and progression of kidney insufficiency and development of end-stage kidney disease in patients with overt diabetic nephropathy in type 2 diabetes mellitus. Associations between baseline proteinuria and proteinuria reduction by either irbesartan, amlodipine, or control for similar decrements in blood pressure and the cumulative incidence of renal end points were examined using the Kaplan-Meier method in patients enrolled in the Irbesartan Diabetic Nephropathy Trial. Risk for kidney failure doubled for each doubling of baseline proteinuria level (hazard ratio, 2.04; 95% confidence interval, 1.87 to 2.22; P < 0.001). For each halving of proteinuria level between baseline and 12 months with treatment, risk for kidney failure was reduced by more than half (hazard ratio, 0.44; 95% confidence interval, 0.40 to 0.49; P < 0.001). For the same proportional change in proteinuria, the reduction in risk for kidney failure was significantly greater for irbesartan compared with amlodipine ( P = 0.048), but not control ( P = 0.245). Proteinuria reduction in the first 12 months of therapy with irbesartan is associated with 36% of the total renoprotective effect observed. Baseline proteinuria is an important risk factor for kidney failure and provides a means to identify patients at greatest risk. Halving proteinuria halves the kidney risk. Proteinuria reduction using an angiotensin receptor-blocking agent, such as irbesartan, should be regarded as an important therapeutic goal in renoprotective strategies.