Patients with end-stage renal disease treated with dialysis are often prescribed complex medicati... more Patients with end-stage renal disease treated with dialysis are often prescribed complex medication regimens, placing them at risk for drug-drug interactions and other medication-related problems. Particularly in the context of a broader interest in more patient-centered value-based care, improving medication management is an increasingly important focus area. However, current medication management metrics, designed for the broader patient population, may not be well suited to the specific needs of patients with kidney disease, especially given the complexity of medication regimens used by dialysis patients. We propose a kidney pharmacy-focused quality pyramid that is intended to provide a framework to guide dialysis organizations, health care providers, and/or clinicians with respect to an optimal medication management approach for dialysis patients. Incorporation of core programs in medication management, including medication reconciliation, safety programs, and medication therapy management for patients at high risk for medication-related problems, may result in improved outcomes. Although a growing body of evidence supports the concept that active medication management can improve medication adherence and reduce medication-related problems, these strategies are viewed as costly and are not widely deployed. However, if done effectively, pharmacy-led medication management has the potential to be one of the more cost-effective disease management strategies and may greatly improve outcomes for these complex patients.
Transplant physicians in the United States continue to face an interesting problem when offering ... more Transplant physicians in the United States continue to face an interesting problem when offering kidney transplantation as a form of renal replacement therapy to older end-stage renal disease (ESRD) patients. The limited life-expectancy of these patients and an ever-present shortage of cadaveric organs makes kidney transplantation in this population a potentially controversial issue. Early results suggested poor outcomes for cadaveric renal transplantation in middle-aged or elderly ESRD patients. Improved patient selection, changes in immunosuppression regimens, and living-related transplantation have increased the success of transplantation in these patients. Efforts to define older patients at risk for cardiovascular disease and to account for their altered immune function may further improve outcomes. However, if older ESRD patients are to be rightfully included in the patient population eligible for transplantation, then the organ shortage will inevitably worsen. A potentially i...
Various malignancies are associated with the paraneoplastic evolution of the nephrotic syndrome. ... more Various malignancies are associated with the paraneoplastic evolution of the nephrotic syndrome. Renal biopsy in these instances frequently shows membranous glomerulonephritis. We describe a patient who had metastatic bronchial carcinoid tumor with development of microscopic hematuria and subsequent nephrotic syndrome in conjunction with another paraneoplastic process, a malignancy-related neuropathy. A decline in actual glomerular filtration rate led to percutaneous renal biopsy, which revealed fine holes in the glomerular basement membrane and focal capillary corrugation. Electron microscopy showed numerous small subepithelial dense deposits and fusion of foot processes, confirming the diagnosis of stage I membranous nephropathy. We believe this is the first published case of true carcinoid tumor associated with the nephrotic syndrome and a specific paraneoplastic glomerular lesion. Carcinoid tumor should be considered in the spectrum of malignancies associated with paraneoplastic development of the nephrotic syndrome.
IMPORTANCE While several studies have demonstrated the benefit of enrollment in chronic condition... more IMPORTANCE While several studies have demonstrated the benefit of enrollment in chronic condition special needs plans (C-SNPs) for other chronic diseases (eg, diabetes), there is no evaluation of the association of C-SNPs with outcomes among patients with end-stage kidney disease (ESKD). OBJECTIVE To examine whether and to what degree C-SNP enrollment was associated with improved clinical outcomes and quality of life in patients with ESKD.
Hypertension is common in CKD, and is a risk factor for faster progression of kidney disease and ... more Hypertension is common in CKD, and is a risk factor for faster progression of kidney disease and development and worsening of CVD. Some antihypertensive agents also slow the progression of kidney disease by mechanisms in addition to their antihypertensive effect. 1.1 Antihypertensive therapy should be used in CKD to: 1.1.a Lower blood pressure (A); 1.1.b Reduce the risk of CVD, in patients with or without hypertension (B) (see Guideline 7); 1.1.c Slow progression of kidney disease, in patients with or without hypertension (A) (see Guidelines 8, 9,10). 1.2 Modifications to antihypertensive therapy should be considered based on the level of proteinuria during treatment (C) (see Guidelines 8, 9, 10,11). 1.3 Antihypertensive therapy should be coordinated with other therapies for CKD as part of a multi-intervention strategy (A). 1.4 If there is a discrepancy between the treatment recommended to slow progression of CKD and to reduce the risk of CVD, individual decision-making should be based on risk stratification (C). BACKGROUND The Joint National Committee (JNC) for Prevention, Detection, Evaluation and Treatment of High Blood Pressure issues regular reports that are meant to provide guidance for primary-care clinicians. The seventh report (JNC 7), issued in 2003, suggests stratification of risk for CVD in individuals with high blood pressure to determine the intensity of treatment. Individuals at highest risk should receive most intensive treatment, including prompt pharmacological therapy, a lower blood pressure goal, and use of specific antihypertensive agents for "compelling indications," including CKD. 5,5a Hypertension is common in CKD, affecting 50% to 75% of individuals. The Work Group for this K/DOQI Guideline on Hypertension and Antihypertensive Agents in CKD proposes recommendations for all patients with CKD, whether or not they have hypertension. Guideline 1 reviews the goals of antihypertensive therapy; multi-intervention strategies for CKD; and possible discrepancies between goals of slowing progression of CKD and reducing CVD risk. It concludes with a review of key recommendations of the guidelines and compares the recommendations to those made by the JNC 7, as well as with previous reports by the NKF and ADA. Limitations, implementation issues, and research recommendations are covered in subsequent guidelines. RATIONALE Definitions Antihypertensive therapy includes lifestyle modifications and pharmacological therapy that reduce blood pressure, in patients with or without hypertension. Lifestyle modifications include changes in diet, exercise, and habits that may slow the progression of CKD or lower the risk of CVD. These guidelines focus specifically on lifestyle modifications that lower blood pressure. Lifestyle modifications are discussed in more detail in Guideline 6. Pharmacological therapy includes selection of antihypertensive agents and blood pressure goals. Antihypertensive agents are defined as agents that lower blood pressure and are usually prescribed to hypertensive individuals for this purpose. Other agents may also lower blood pressure as a side-effect. It is important to note that antihypertensive agents may have salutary effects on CKD and CVD in addition to lowering systemic blood pressure, such as reducing proteinuria, slowing GFR decline, and inhibiting other pathogenetic mechanisms of kidney disease progression and CVD. General principles of pharmacological therapy and target blood pressure for reducing CVD risk are discussed in Guideline 7. "Preferred agents." Classes of antihypertensive agents that have beneficial effects on progression of CKD or reducing CVD risk, in addition to their antihypertensive effects, are defined as "preferred agents" for those conditions. Preferred agents for specific types of CVD are discussed in Guideline 7. In certain types of CKD, specific classes of antihypertensive agents, notably those that inhibit the renin-angiotensin system (RAS), are preferred agents for slowing progression of kidney disease. Thus, the guidelines recommend the use of specific classes of antihypertensive agents in certain types of CKD, even if hypertension is not present. These agents also reduce proteinuria and may be considered for this purpose as well. Preferred agents for CKD are discussed in Guidelines 8 through 10. ACE inhibitors and angiotensin receptor blockers are discussed in Guideline 11, and diuretics are discussed in Guideline 12. Strength of Evidence Patients with CKD are in the "highest-risk" group for CVD (Strong). Patients with CKD are at increased risk of CVD. Hypertension is a risk factor for CVD events in CKD. However, there have been few controlled trials to demonstrate the efficacy of blood pressure lowering to reduce the risk of CVD in CKD; therefore, the Work Group made recommendations for CKD based on extrapolation from evidence on the efficacy of antihypertensive therapy in the general population. Because of the high risk of CVD in CKD, the Work Group concluded that individuals with CKD should be included in the "highest-risk group" for implementation of antihypertensive therapy to reduce CVD risk. Table 42 shows recommendations from JNC 7 for the highest-risk group. Guideline 7 discusses the appropriate blood pressure target to reduce risk of CVD in the highest-risk group. Some classes of antihypertensive agents are preferred in certain types of CKD (Strong). Most patients with CKD experience progressive GFR decline over time. Hypertension is a risk factor for faster progression of kidney disease. In addition, some other modifiable risk factors (proteinuria and activity of the RAS) are also affected by antihypertensive therapy. RCTs demonstrate that some classes of antihypertensive agents (notably, those that inhibit the RAS) are "preferred agents" for slowing progression of specific types of CKD. In addition, for some types of CKD, the blood pressure goal recommended for CVD risk reduction in high-risk groups has been shown to slow the progression of CKD. Thus, the Work Group recommended that antihypertensive therapy in CKD also be guided by the type of kidney disease. Table 43 shows general recommendations to slow the progression of CKD. Guidelines 8 through 10 discuss specific types of CKD. Level of proteinuria and changes in the level of proteinuria may be a guide to modifications of antihypertensive therapy (Weak). Proteinuria is important in CKD for a number of reasons. It is a marker for kidney damage, a clue to the type (diagnosis of CKD), and a risk factor for faster progression of kidney disease and development of CVD, and it identifies patients who benefit more from preferred agents and a lower target blood pressure (Table 29). In addition, it has been hypothesized that changes in the level of proteinuria during treatment may be a surrogate widely used guidelines for treatment of individuals with hypertension and diabetes the two most common causes of CKD. During the Work Group s meetings, JNC 6 15 and ADA 2002 115,116 were available. Risk stratification (Table 47). JNC 6 suggested risk stratification of individuals with hypertension for therapeutic decisions. 15 Although JNC 7 simplified this classification, the Work Group found the concepts useful in its deliberations. There is a spectrum of risk from very high to low, and patients were classified into three general risk categories. Patients at "low risk" (Group A) were defined as those without pre-existing CVD or target organ damage, without diabetes, and with no other risk factors for CVD other than hypertension. Patients at "high risk" (Group B) were defined as those without CVD or target organ damage, without diabetes, but with one or more with other risk factors for CVD. Patients at "very high risk" (Group C) were defined as those with CVD, target organ damage, or compelling indications, such as diabetes and CKD. Because there are few studies of antihypertensive therapy on CVD in CKD and because patients with CKD are in the highest-risk category for CVD, the Work Group recommends extrapolating the results from studies in the general population and other highest-risk populations to CKD (see Guideline 7).
Journal of the American Society of Nephrology : JASN, 2001
The discovery of insulin in 1922 changed the treatment of type 1 diabetes mellitus (DM) forever. ... more The discovery of insulin in 1922 changed the treatment of type 1 diabetes mellitus (DM) forever. Insulin was the first effective therapy for type 1 DM; however, its success engendered a terrible paradox for patients with this disease. The use of insulin transformed type 1 DM from a rapidly fatal condition to a chronic incurable illness, revealing the long-term complications associated with DM, e.g., nephropathy, vasculopathy, retinopathy, and neuropathy, and the terrible toll that they take throughout a lifetime. DM now affects approximately 20 million individuals in the United States, with at least 2 million individuals having classic type 1 DM (1). Hyperglycemia, alone or in concert with hypertension, is the primary factor influencing the development of major diabetic complications (2,3). Therefore, correcting hyperglycemia is an obvious strategy for altering the course of DM and its complications. The Diabetes Control and Complications Trial (4) demonstrated that glycemic control...
OBJECTIVE To examine the likelihood of transplantation and trends over time among persons with en... more OBJECTIVE To examine the likelihood of transplantation and trends over time among persons with end-stage renal disease (ESRD) in Wisconsin. METHODS We examined the influence of patient- and community-level characteristics on the rate of kidney transplantation in Wisconsin among 22,387 patients diagnosed with ESRD between January 1, 1982 and October 30, 2005. We grouped patients by the year of ESRD onset in order to model the change in transplantation rates over time. RESULTS After multivariate adjustment, all other racial groups were significantly less likely to be transplanted compared with whites, and the racial disparity increased over calendar time. Older patients were less likely to be transplanted in all periods. Higher community income and education level and a greater distance from patients' residence to the nearest dialysis center significantly increased the likelihood of transplantation. Males also had a significantly higher rate of transplantation than females. CONCLU...
Wolters Kluwer Health may email you for journal alerts and information, but is committed to maint... more Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... Skip Navigation Links Home > July 15, ...
Chronic allograft nephropathy (CAN) remains a major barrier to long-term allograft survival. The ... more Chronic allograft nephropathy (CAN) remains a major barrier to long-term allograft survival. The authors retrospectively compared the development of CAN in recipients of cadaveric (CAD), living-related donor (LRD), and living-unrelated donor (LURD) transplants at their center. The authors retrospectively examined the impact of various factors on the incidence of CAN using univariate and multivariate proportional hazards analysis in a single-center kidney transplant population. Between 1 January 1990 and 31 May 2000, 2,140 kidney-alone transplants were performed at the authors' center. The overall 5-year incidence of biopsy-proven CAN was 12.2% (n=203). Risk factors for CAN included the number of transplants (P=0.0001), acute rejection (P=0.0001), panel reactive antibody (P=0.0001), discharge creatinine (P=0.0001), 1-year creatinine (P=0.0015), delayed graft function (P=0.007), total human leukocyte antigen (HLA)-B and -DR mismatches (P=0.0005), recipient age (P=0.003), black donor race (P=0.001), black recipient race (0.0457), donor age (P=0.0053), cold storage time (P=0.019), and cytomegalovirus infections (P=0.002). Interestingly, although the LRD HLA-identical recipients had a significantly lower incidence of CAN (P=0.0015), the incidence of CAN in CAD and HLA-nonidentical LRD recipients did not differ. Graft survival was significantly worse in CAD recipients compared with all other groups (P<0.001). These results demonstrate the importance of immunologic and nonimmunologic factors on the development of CAN. The disparities in overall graft survival, despite the similarities in CAN rates, suggests that other factors, in addition to CAN, influence the increase in graft loss in CAD transplant recipients.
To determine whether patients with tertiary hyperparathyroidism due to single-or two-gland diseas... more To determine whether patients with tertiary hyperparathyroidism due to single-or two-gland disease undergoing limited resection have similar long-term outcomes compared with patients with hyperplasia undergoing subtotal or total parathyroidectomy. Summary Background Data Tertiary hyperparathyroidism occurs in less than 2% of patients after renal transplantation. Approximately 30% of these cases are caused by one or two hyperfunctioning glands. Nevertheless, the standard operation for this disease has been subtotal or total parathyroidectomy with autotransplantation.
Background: Disease progression rates and outcomes per stage of kidney disease in kidney transpla... more Background: Disease progression rates and outcomes per stage of kidney disease in kidney transplant recipients with type 1 diabetes mellitus are unknown. Study Design: Single-center retrospective cohort study. Settings & Participants: 276 kidney transplant recipients with type 1 diabetes mellitus and a functioning graft at 1 year posttransplantation. Predictors: Stage of chronic kidney disease at 1 year posttransplantation, donor source, and other clinical characteristics (covariates). Outcomes & Measurements: Slope of creatinine clearance, weighted average slopes of creatinine clearance in a subgroup of 60 patients, death-censored allograft and patient survival rates. Results: The median rate of creatinine clearance decrease after the first posttransplantation year was Ϫ1.6 mL/min/y (95% confidence interval [CI], Ϫ1.97 to Ϫ1.30) during a median follow-up of 8.4 years (95% CI, 8.13 to 8.84). The slope was significantly greater in stages 1 to 2 (Ϫ1.7 mL/min/y; 95% CI, Ϫ2.2 to Ϫ1.4) than stage 3 (Ϫ1.2 mL/min/y; 95% CI, Ϫ1.9 to Ϫ0.6; P ϭ 0.0003). However, chronic kidney disease stage and donor source had no significant effect on death-censored allograft survival and patient survival rates. There were 23 deaths and 31 allograft losses in patients with stages 1 to 2 compared with 19 deaths and 18 allograft losses in those with stage 3. Univariate and multivariable Cox regression analyses showed that semiquantitative proteinuria of 1 or greater, mean arterial pressure, hematocrit of 33% or less, and calcineurin-inhibitor use were associated with decreased allograft survival, and age and hemoglobin A 1c level of 7% or greater were significant risk factors for patient death regardless of donor type and stage of kidney function. Limitations: Generalizability to other settings; study power. Conclusion: All forms of kidney transplantation in patients with type 1 diabetes mellitus progressed at similar rates regardless of chronic kidney disease stage at 1 year posttransplantation. Age, anemia, hemoglobin A 1c level, proteinuria, hypertension, and calcineurin-inhibitor use were associated with decreased allograft and patient outcomes.
Registry analyses and single-center studies have demonstrated that hypertension significantly inc... more Registry analyses and single-center studies have demonstrated that hypertension significantly increases the risk for chronic graft loss. The graft itself may contribute to posttransplant hypertension, and intragraft vasoactive hormones therefore, may be dysregulated in posttransplant hypertension. We used the reverse-transcription polymerase chain reaction to assess the intragraft regulation of renin-angiotensin system transcripts in biopsy samples from 42 stable renal transplant patients with posttransplant hypertension. We also examined mRNA expression of inducible nitric oxide synthase, transforming growth factor-beta (TGF-beta), select cytokines, and metalloproteinase transcripts in biopsy tissue. Polymerase chain reaction products were quantitated using high performance liquid chromatography and normalized to beta-actin mRNA expression. Serum creatinine, glomerular filtration rate or creatinine clearance and tubular atrophy on biopsy were concurrently assessed. Renin and select Thl cytokine mRNA expression correlated with blood pressure. Type 1 angiotensin II receptor mRNA expression significantly correlated with glomerular filtration rate or creatinine clearance (P = 0.034) and inversely correlated with Th1 cytokines, inducible nitric oxide synthase, and cyclooxygenase-1 mRNA expression (P< or =0.013 for each). Type 1 angiotensin II receptor mRNA also approached a significant inverse correlation with TGF-beta mRNA expression (P = 0.09). Conversely, angiotensin-converting enzyme mRNA expression directly correlated with Thl cytokine (P< or =0.008 for each) and TGF-beta mRNA expression (P = 0.006). Type 1 angiotensin II receptor mRNA expression also correlated with matrix metalloproteinase-1 promoter region, tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and tissue inhibitor of matrix metalloproteinase-3 mRNA expression. Notably, matrix metalloproteinase-1 promoter region, tissue inhibitor of matrix metalloproteinase-2, and tissue inhibitor of matrix metalloproteinase-3 inversely correlated with TGF-beta mRNA expression (P< or =0.0027 for each). Type 1 angiotensin II receptor mRNA expression at biopsy directly correlated with glomerular filtration rate at 2 year's follow-up. However, angiotensin-converting enzyme mRNA expression at biopsy inversely correlated with glomerular filtration rate at 2 year's follow-up. These data suggest that allograft-level RAS gene expression may be predictive of future graft function in the setting of diastolic hypertension.
Patients with end-stage renal disease treated with dialysis are often prescribed complex medicati... more Patients with end-stage renal disease treated with dialysis are often prescribed complex medication regimens, placing them at risk for drug-drug interactions and other medication-related problems. Particularly in the context of a broader interest in more patient-centered value-based care, improving medication management is an increasingly important focus area. However, current medication management metrics, designed for the broader patient population, may not be well suited to the specific needs of patients with kidney disease, especially given the complexity of medication regimens used by dialysis patients. We propose a kidney pharmacy-focused quality pyramid that is intended to provide a framework to guide dialysis organizations, health care providers, and/or clinicians with respect to an optimal medication management approach for dialysis patients. Incorporation of core programs in medication management, including medication reconciliation, safety programs, and medication therapy management for patients at high risk for medication-related problems, may result in improved outcomes. Although a growing body of evidence supports the concept that active medication management can improve medication adherence and reduce medication-related problems, these strategies are viewed as costly and are not widely deployed. However, if done effectively, pharmacy-led medication management has the potential to be one of the more cost-effective disease management strategies and may greatly improve outcomes for these complex patients.
Transplant physicians in the United States continue to face an interesting problem when offering ... more Transplant physicians in the United States continue to face an interesting problem when offering kidney transplantation as a form of renal replacement therapy to older end-stage renal disease (ESRD) patients. The limited life-expectancy of these patients and an ever-present shortage of cadaveric organs makes kidney transplantation in this population a potentially controversial issue. Early results suggested poor outcomes for cadaveric renal transplantation in middle-aged or elderly ESRD patients. Improved patient selection, changes in immunosuppression regimens, and living-related transplantation have increased the success of transplantation in these patients. Efforts to define older patients at risk for cardiovascular disease and to account for their altered immune function may further improve outcomes. However, if older ESRD patients are to be rightfully included in the patient population eligible for transplantation, then the organ shortage will inevitably worsen. A potentially i...
Various malignancies are associated with the paraneoplastic evolution of the nephrotic syndrome. ... more Various malignancies are associated with the paraneoplastic evolution of the nephrotic syndrome. Renal biopsy in these instances frequently shows membranous glomerulonephritis. We describe a patient who had metastatic bronchial carcinoid tumor with development of microscopic hematuria and subsequent nephrotic syndrome in conjunction with another paraneoplastic process, a malignancy-related neuropathy. A decline in actual glomerular filtration rate led to percutaneous renal biopsy, which revealed fine holes in the glomerular basement membrane and focal capillary corrugation. Electron microscopy showed numerous small subepithelial dense deposits and fusion of foot processes, confirming the diagnosis of stage I membranous nephropathy. We believe this is the first published case of true carcinoid tumor associated with the nephrotic syndrome and a specific paraneoplastic glomerular lesion. Carcinoid tumor should be considered in the spectrum of malignancies associated with paraneoplastic development of the nephrotic syndrome.
IMPORTANCE While several studies have demonstrated the benefit of enrollment in chronic condition... more IMPORTANCE While several studies have demonstrated the benefit of enrollment in chronic condition special needs plans (C-SNPs) for other chronic diseases (eg, diabetes), there is no evaluation of the association of C-SNPs with outcomes among patients with end-stage kidney disease (ESKD). OBJECTIVE To examine whether and to what degree C-SNP enrollment was associated with improved clinical outcomes and quality of life in patients with ESKD.
Hypertension is common in CKD, and is a risk factor for faster progression of kidney disease and ... more Hypertension is common in CKD, and is a risk factor for faster progression of kidney disease and development and worsening of CVD. Some antihypertensive agents also slow the progression of kidney disease by mechanisms in addition to their antihypertensive effect. 1.1 Antihypertensive therapy should be used in CKD to: 1.1.a Lower blood pressure (A); 1.1.b Reduce the risk of CVD, in patients with or without hypertension (B) (see Guideline 7); 1.1.c Slow progression of kidney disease, in patients with or without hypertension (A) (see Guidelines 8, 9,10). 1.2 Modifications to antihypertensive therapy should be considered based on the level of proteinuria during treatment (C) (see Guidelines 8, 9, 10,11). 1.3 Antihypertensive therapy should be coordinated with other therapies for CKD as part of a multi-intervention strategy (A). 1.4 If there is a discrepancy between the treatment recommended to slow progression of CKD and to reduce the risk of CVD, individual decision-making should be based on risk stratification (C). BACKGROUND The Joint National Committee (JNC) for Prevention, Detection, Evaluation and Treatment of High Blood Pressure issues regular reports that are meant to provide guidance for primary-care clinicians. The seventh report (JNC 7), issued in 2003, suggests stratification of risk for CVD in individuals with high blood pressure to determine the intensity of treatment. Individuals at highest risk should receive most intensive treatment, including prompt pharmacological therapy, a lower blood pressure goal, and use of specific antihypertensive agents for "compelling indications," including CKD. 5,5a Hypertension is common in CKD, affecting 50% to 75% of individuals. The Work Group for this K/DOQI Guideline on Hypertension and Antihypertensive Agents in CKD proposes recommendations for all patients with CKD, whether or not they have hypertension. Guideline 1 reviews the goals of antihypertensive therapy; multi-intervention strategies for CKD; and possible discrepancies between goals of slowing progression of CKD and reducing CVD risk. It concludes with a review of key recommendations of the guidelines and compares the recommendations to those made by the JNC 7, as well as with previous reports by the NKF and ADA. Limitations, implementation issues, and research recommendations are covered in subsequent guidelines. RATIONALE Definitions Antihypertensive therapy includes lifestyle modifications and pharmacological therapy that reduce blood pressure, in patients with or without hypertension. Lifestyle modifications include changes in diet, exercise, and habits that may slow the progression of CKD or lower the risk of CVD. These guidelines focus specifically on lifestyle modifications that lower blood pressure. Lifestyle modifications are discussed in more detail in Guideline 6. Pharmacological therapy includes selection of antihypertensive agents and blood pressure goals. Antihypertensive agents are defined as agents that lower blood pressure and are usually prescribed to hypertensive individuals for this purpose. Other agents may also lower blood pressure as a side-effect. It is important to note that antihypertensive agents may have salutary effects on CKD and CVD in addition to lowering systemic blood pressure, such as reducing proteinuria, slowing GFR decline, and inhibiting other pathogenetic mechanisms of kidney disease progression and CVD. General principles of pharmacological therapy and target blood pressure for reducing CVD risk are discussed in Guideline 7. "Preferred agents." Classes of antihypertensive agents that have beneficial effects on progression of CKD or reducing CVD risk, in addition to their antihypertensive effects, are defined as "preferred agents" for those conditions. Preferred agents for specific types of CVD are discussed in Guideline 7. In certain types of CKD, specific classes of antihypertensive agents, notably those that inhibit the renin-angiotensin system (RAS), are preferred agents for slowing progression of kidney disease. Thus, the guidelines recommend the use of specific classes of antihypertensive agents in certain types of CKD, even if hypertension is not present. These agents also reduce proteinuria and may be considered for this purpose as well. Preferred agents for CKD are discussed in Guidelines 8 through 10. ACE inhibitors and angiotensin receptor blockers are discussed in Guideline 11, and diuretics are discussed in Guideline 12. Strength of Evidence Patients with CKD are in the "highest-risk" group for CVD (Strong). Patients with CKD are at increased risk of CVD. Hypertension is a risk factor for CVD events in CKD. However, there have been few controlled trials to demonstrate the efficacy of blood pressure lowering to reduce the risk of CVD in CKD; therefore, the Work Group made recommendations for CKD based on extrapolation from evidence on the efficacy of antihypertensive therapy in the general population. Because of the high risk of CVD in CKD, the Work Group concluded that individuals with CKD should be included in the "highest-risk group" for implementation of antihypertensive therapy to reduce CVD risk. Table 42 shows recommendations from JNC 7 for the highest-risk group. Guideline 7 discusses the appropriate blood pressure target to reduce risk of CVD in the highest-risk group. Some classes of antihypertensive agents are preferred in certain types of CKD (Strong). Most patients with CKD experience progressive GFR decline over time. Hypertension is a risk factor for faster progression of kidney disease. In addition, some other modifiable risk factors (proteinuria and activity of the RAS) are also affected by antihypertensive therapy. RCTs demonstrate that some classes of antihypertensive agents (notably, those that inhibit the RAS) are "preferred agents" for slowing progression of specific types of CKD. In addition, for some types of CKD, the blood pressure goal recommended for CVD risk reduction in high-risk groups has been shown to slow the progression of CKD. Thus, the Work Group recommended that antihypertensive therapy in CKD also be guided by the type of kidney disease. Table 43 shows general recommendations to slow the progression of CKD. Guidelines 8 through 10 discuss specific types of CKD. Level of proteinuria and changes in the level of proteinuria may be a guide to modifications of antihypertensive therapy (Weak). Proteinuria is important in CKD for a number of reasons. It is a marker for kidney damage, a clue to the type (diagnosis of CKD), and a risk factor for faster progression of kidney disease and development of CVD, and it identifies patients who benefit more from preferred agents and a lower target blood pressure (Table 29). In addition, it has been hypothesized that changes in the level of proteinuria during treatment may be a surrogate widely used guidelines for treatment of individuals with hypertension and diabetes the two most common causes of CKD. During the Work Group s meetings, JNC 6 15 and ADA 2002 115,116 were available. Risk stratification (Table 47). JNC 6 suggested risk stratification of individuals with hypertension for therapeutic decisions. 15 Although JNC 7 simplified this classification, the Work Group found the concepts useful in its deliberations. There is a spectrum of risk from very high to low, and patients were classified into three general risk categories. Patients at "low risk" (Group A) were defined as those without pre-existing CVD or target organ damage, without diabetes, and with no other risk factors for CVD other than hypertension. Patients at "high risk" (Group B) were defined as those without CVD or target organ damage, without diabetes, but with one or more with other risk factors for CVD. Patients at "very high risk" (Group C) were defined as those with CVD, target organ damage, or compelling indications, such as diabetes and CKD. Because there are few studies of antihypertensive therapy on CVD in CKD and because patients with CKD are in the highest-risk category for CVD, the Work Group recommends extrapolating the results from studies in the general population and other highest-risk populations to CKD (see Guideline 7).
Journal of the American Society of Nephrology : JASN, 2001
The discovery of insulin in 1922 changed the treatment of type 1 diabetes mellitus (DM) forever. ... more The discovery of insulin in 1922 changed the treatment of type 1 diabetes mellitus (DM) forever. Insulin was the first effective therapy for type 1 DM; however, its success engendered a terrible paradox for patients with this disease. The use of insulin transformed type 1 DM from a rapidly fatal condition to a chronic incurable illness, revealing the long-term complications associated with DM, e.g., nephropathy, vasculopathy, retinopathy, and neuropathy, and the terrible toll that they take throughout a lifetime. DM now affects approximately 20 million individuals in the United States, with at least 2 million individuals having classic type 1 DM (1). Hyperglycemia, alone or in concert with hypertension, is the primary factor influencing the development of major diabetic complications (2,3). Therefore, correcting hyperglycemia is an obvious strategy for altering the course of DM and its complications. The Diabetes Control and Complications Trial (4) demonstrated that glycemic control...
OBJECTIVE To examine the likelihood of transplantation and trends over time among persons with en... more OBJECTIVE To examine the likelihood of transplantation and trends over time among persons with end-stage renal disease (ESRD) in Wisconsin. METHODS We examined the influence of patient- and community-level characteristics on the rate of kidney transplantation in Wisconsin among 22,387 patients diagnosed with ESRD between January 1, 1982 and October 30, 2005. We grouped patients by the year of ESRD onset in order to model the change in transplantation rates over time. RESULTS After multivariate adjustment, all other racial groups were significantly less likely to be transplanted compared with whites, and the racial disparity increased over calendar time. Older patients were less likely to be transplanted in all periods. Higher community income and education level and a greater distance from patients' residence to the nearest dialysis center significantly increased the likelihood of transplantation. Males also had a significantly higher rate of transplantation than females. CONCLU...
Wolters Kluwer Health may email you for journal alerts and information, but is committed to maint... more Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... Skip Navigation Links Home > July 15, ...
Chronic allograft nephropathy (CAN) remains a major barrier to long-term allograft survival. The ... more Chronic allograft nephropathy (CAN) remains a major barrier to long-term allograft survival. The authors retrospectively compared the development of CAN in recipients of cadaveric (CAD), living-related donor (LRD), and living-unrelated donor (LURD) transplants at their center. The authors retrospectively examined the impact of various factors on the incidence of CAN using univariate and multivariate proportional hazards analysis in a single-center kidney transplant population. Between 1 January 1990 and 31 May 2000, 2,140 kidney-alone transplants were performed at the authors' center. The overall 5-year incidence of biopsy-proven CAN was 12.2% (n=203). Risk factors for CAN included the number of transplants (P=0.0001), acute rejection (P=0.0001), panel reactive antibody (P=0.0001), discharge creatinine (P=0.0001), 1-year creatinine (P=0.0015), delayed graft function (P=0.007), total human leukocyte antigen (HLA)-B and -DR mismatches (P=0.0005), recipient age (P=0.003), black donor race (P=0.001), black recipient race (0.0457), donor age (P=0.0053), cold storage time (P=0.019), and cytomegalovirus infections (P=0.002). Interestingly, although the LRD HLA-identical recipients had a significantly lower incidence of CAN (P=0.0015), the incidence of CAN in CAD and HLA-nonidentical LRD recipients did not differ. Graft survival was significantly worse in CAD recipients compared with all other groups (P<0.001). These results demonstrate the importance of immunologic and nonimmunologic factors on the development of CAN. The disparities in overall graft survival, despite the similarities in CAN rates, suggests that other factors, in addition to CAN, influence the increase in graft loss in CAD transplant recipients.
To determine whether patients with tertiary hyperparathyroidism due to single-or two-gland diseas... more To determine whether patients with tertiary hyperparathyroidism due to single-or two-gland disease undergoing limited resection have similar long-term outcomes compared with patients with hyperplasia undergoing subtotal or total parathyroidectomy. Summary Background Data Tertiary hyperparathyroidism occurs in less than 2% of patients after renal transplantation. Approximately 30% of these cases are caused by one or two hyperfunctioning glands. Nevertheless, the standard operation for this disease has been subtotal or total parathyroidectomy with autotransplantation.
Background: Disease progression rates and outcomes per stage of kidney disease in kidney transpla... more Background: Disease progression rates and outcomes per stage of kidney disease in kidney transplant recipients with type 1 diabetes mellitus are unknown. Study Design: Single-center retrospective cohort study. Settings & Participants: 276 kidney transplant recipients with type 1 diabetes mellitus and a functioning graft at 1 year posttransplantation. Predictors: Stage of chronic kidney disease at 1 year posttransplantation, donor source, and other clinical characteristics (covariates). Outcomes & Measurements: Slope of creatinine clearance, weighted average slopes of creatinine clearance in a subgroup of 60 patients, death-censored allograft and patient survival rates. Results: The median rate of creatinine clearance decrease after the first posttransplantation year was Ϫ1.6 mL/min/y (95% confidence interval [CI], Ϫ1.97 to Ϫ1.30) during a median follow-up of 8.4 years (95% CI, 8.13 to 8.84). The slope was significantly greater in stages 1 to 2 (Ϫ1.7 mL/min/y; 95% CI, Ϫ2.2 to Ϫ1.4) than stage 3 (Ϫ1.2 mL/min/y; 95% CI, Ϫ1.9 to Ϫ0.6; P ϭ 0.0003). However, chronic kidney disease stage and donor source had no significant effect on death-censored allograft survival and patient survival rates. There were 23 deaths and 31 allograft losses in patients with stages 1 to 2 compared with 19 deaths and 18 allograft losses in those with stage 3. Univariate and multivariable Cox regression analyses showed that semiquantitative proteinuria of 1 or greater, mean arterial pressure, hematocrit of 33% or less, and calcineurin-inhibitor use were associated with decreased allograft survival, and age and hemoglobin A 1c level of 7% or greater were significant risk factors for patient death regardless of donor type and stage of kidney function. Limitations: Generalizability to other settings; study power. Conclusion: All forms of kidney transplantation in patients with type 1 diabetes mellitus progressed at similar rates regardless of chronic kidney disease stage at 1 year posttransplantation. Age, anemia, hemoglobin A 1c level, proteinuria, hypertension, and calcineurin-inhibitor use were associated with decreased allograft and patient outcomes.
Registry analyses and single-center studies have demonstrated that hypertension significantly inc... more Registry analyses and single-center studies have demonstrated that hypertension significantly increases the risk for chronic graft loss. The graft itself may contribute to posttransplant hypertension, and intragraft vasoactive hormones therefore, may be dysregulated in posttransplant hypertension. We used the reverse-transcription polymerase chain reaction to assess the intragraft regulation of renin-angiotensin system transcripts in biopsy samples from 42 stable renal transplant patients with posttransplant hypertension. We also examined mRNA expression of inducible nitric oxide synthase, transforming growth factor-beta (TGF-beta), select cytokines, and metalloproteinase transcripts in biopsy tissue. Polymerase chain reaction products were quantitated using high performance liquid chromatography and normalized to beta-actin mRNA expression. Serum creatinine, glomerular filtration rate or creatinine clearance and tubular atrophy on biopsy were concurrently assessed. Renin and select Thl cytokine mRNA expression correlated with blood pressure. Type 1 angiotensin II receptor mRNA expression significantly correlated with glomerular filtration rate or creatinine clearance (P = 0.034) and inversely correlated with Th1 cytokines, inducible nitric oxide synthase, and cyclooxygenase-1 mRNA expression (P< or =0.013 for each). Type 1 angiotensin II receptor mRNA also approached a significant inverse correlation with TGF-beta mRNA expression (P = 0.09). Conversely, angiotensin-converting enzyme mRNA expression directly correlated with Thl cytokine (P< or =0.008 for each) and TGF-beta mRNA expression (P = 0.006). Type 1 angiotensin II receptor mRNA expression also correlated with matrix metalloproteinase-1 promoter region, tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and tissue inhibitor of matrix metalloproteinase-3 mRNA expression. Notably, matrix metalloproteinase-1 promoter region, tissue inhibitor of matrix metalloproteinase-2, and tissue inhibitor of matrix metalloproteinase-3 inversely correlated with TGF-beta mRNA expression (P< or =0.0027 for each). Type 1 angiotensin II receptor mRNA expression at biopsy directly correlated with glomerular filtration rate at 2 year's follow-up. However, angiotensin-converting enzyme mRNA expression at biopsy inversely correlated with glomerular filtration rate at 2 year's follow-up. These data suggest that allograft-level RAS gene expression may be predictive of future graft function in the setting of diastolic hypertension.
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Papers by Bryan Becker