Risk Of Kidney Disease Progression Research Articles

Hyperuricemia Predicts Kidney Disease Progression After Acute Allograft Dysfunction

BackgroundHyperuricemia is associated with the development of new cardiovascular events and chronic allograft nephropathy in patients with decreased allograft function. This study investigates whether hyperuricemia in kidney transplant recipients should be considered as an independent predictor of kidney disease progression after acute allograft dysfunction. MethodsBetween September 1, 2010, and December 31, 2012, 124 patients who underwent kidney graft biopsy for acute allograft dysfunction were enrolled. Participants were divided into 2 groups: A hyperuricemic group (n = 57) and a normouricemic group (n = 67). The mean serum uric acid (UA) level was obtained by averaging all measurements, once per month for 3 months, before the study began. Clinical and laboratory data were collected. We investigated the role of hyperuricemia on the composite end point (CEP) of doubling of serum creatinine and graft failure by using Cox regression and Kaplan-Meier plots. ResultsOver a mean follow-up of 14.27 months, the hyperuricemic group had a poor cumulative survival and easily reached the CEP of doubling of serum creatinine and graft failure (P = .025) with a first-year cumulative incidence of 29.84% and a second-year cumulative incidence of 35.09%. Cox regression models revealed that age at biopsy (unadjusted hazard ratio [HR], 1.03; 95% CI, 1.00–1.06), hyperuricemia (HR, 2.24; 95% CI, 1.13–4.46), and interstitial fibrosis and tubular atrophy (IF/TA), including <25% of parenchyma affected (HR, 3.71; 95% CI, 1.34–10.31) and ≥25% of parenchyma affected (HR, 5.10; 95% CI, 1.83–14.19), were highly associated with poor outcome. After adjusting different variables, hyperuricemia and IF/TA were still significant. ConclusionPersistently high serum UA and IF/TA both contribute to the risk of kidney disease progression after acute allograft dysfunction.

Meta-Analysis of Association between Pathological Characteristics and Renal Outcomes in Adult Idiopathic Membranous Nephropathy

Background and objectives: The associations of pathological features with renal outcomes in adult Idiopathic Membranous Nephropathy (IMN) are still controversial. A meta-analysis was performed to assess whether pathological features could independently predict risk of progressive kidney disease in adult IMN patients. Methods: The PubMed database (January 2000 to September 2013) was searched to identify cohort studies of adult IMN patients (≥ 50 patients for each study) in which at least one of the following pathological features was assessed: segmental sclerosis, tubular atrophy/interstitial fibrosis, arteriosclerosis, C3 deposits by immunofluorescence, and the stage or heterogeneity of electron dense deposits by electron microscopy. Renal outcomes included development of renal insufficiency or progression to ESRD. Results: Nine cohort studies were included. A total of 2080 patients with 252 hard endpoints (renal insufficiency or ESRD) were reported. Segmental sclerosis was significantly associated with poor renal outcomes (8 studies with 1622 patients: hazard ratio, 1.59 [95% confidence interval, 1.07-2.37], P=0.02). Tubular atrophy/interstitial fibrosis and arteriosclerosis were also significantly associated with poor renal outcomes (7 studies with 1569 patients: 3.85 [2.16-6.87], P<0.000001; and 5 studies with 1349 patients: 1.83 [1.17-2.86], P=0.008). There were insufficient data to systematically assess the independent predictive value of C3 deposits and the stage and heterogeneity of electron dense deposits. Conclusions: Significant associations of renal outcomes with segmental sclerosis, chronic tubule interstitial injury, and arteriosclerosis were only confirmed in two, five, and one of nine included studies, respectively. However, this meta-analysis indicated that each of these pathological features was significantly associated with progression of kidney disease. More methodologically sound and sufficiently powered prospective cohort studies with adequate number of patients and length of follow-up are still urgently needed to address the questions regarding prognostic utility of pathological features in adult IMN patients.

Baseline Kidney Function as Predictor of Mortality and Kidney Disease Progression in HIV-Positive Patients

BackgroundChronic kidney disease (CKD) is associated with increased all-cause mortality and kidney disease progression. Decreased kidney function at baseline may identify human immunodeficiency virus (HIV)-positive patients at increased risk of death and kidney disease progression.Study DesignObservational cohort study.Setting & Participants7 large HIV cohorts in the United Kingdom with kidney function data available for 20,132 patients.PredictorBaseline estimated glomerular filtration rate (eGFR).OutcomesDeath and progression to stages 4-5 CKD (eGFR <30 mL/min/1.73 m2 for >3 months) in Cox proportional hazards and competing-risk regression models.ResultsMedian age at baseline was 34 (25th-75th percentile, 30-40) years, median CD4 cell count was 350 (25th-75th percentile, 208-520) cells/μL, and median eGFR was 100 (25th-75th percentile, 87-112) mL/min/1.73 m2. Patients were followed up for a median of 5.3 (25th-75th percentile, 2.0-8.9) years, during which 1,820 died and 56 progressed to stages 4-5 CKD. A U-shaped relationship between baseline eGFR and mortality was observed. After adjustment for potential confounders, eGFRs <45 and >105 mL/min/1.73 m2 remained associated significantly with increased risk of death. Baseline eGFR <90 mL/min/1.73 m2 was associated with increased risk of kidney disease progression, with the highest incidence rates of stages 4-5 CKD (>3 events/100 person-years) observed in black patients with eGFR of 30-59 mL/min/1.73 m2 and those of white/other ethnicity with eGFR of 30-44 mL/min/1.73 m2.LimitationsThe relatively small numbers of patients with decreased eGFR at baseline and low rates of progression to stages 4-5 CKD and lack of data for diabetes, hypertension, and proteinuria.ConclusionsAlthough stages 4-5 CKD were uncommon in this cohort, baseline eGFR allowed the identification of patients at increased risk of death and at greatest risk of kidney disease progression.

A reappraisal of renin–angiotensin system blockade on microalbuminuria development

A reappraisal of renin–angiotensin system blockade on microalbuminuria development

Defective renal maintenance of the vitamin D endocrine system impairs vitamin D renoprotection: a downward spiral in kidney disease

In kidney disease, the progressive loss of renal capacity to produce calcitriol, the vitamin D hormone, is a key contributor to elevations in parathyroid hormone (PTH) and mineral and skeletal disorders predisposing to renal and cardiovascular damage, ectopic calcifications, and high mortality rates. Thus, the safe correction of calcitriol deficiency to suppress PTH has been the treatment of choice for decades. However, recent epidemiological and experimental data suggest that calcitriol replacement may improve outcomes through renal and cardioprotective actions unrelated to PTH suppression. Furthermore, a striking incidence of vitamin D deficiency occurs in kidney disease and associates more strongly than calcitriol deficiency with a higher risk for kidney disease progression and death. Despite the translational relevance of these findings, no prospective trials are currently available in support of the efficacy of vitamin D supplementation and/or calcitriol replacement to safely halt/moderate renal disease progression. This review updates the pathophysiology behind the vicious cycle by which kidney injury impairs the maintenance of normal vitamin D and calcitriol levels, which in turn impedes vitamin D/calcitriol renoprotective actions, a requirement for the design of prospective trials to improve current recommendations for vitamin D interventions at all stages of kidney disease.

Tertiary excess of fibroblast growth factor 23 and hypophosphatemia following kidney transplantation

Hypophosphatemia caused by inappropriate urinary phosphate wasting is a frequent metabolic complication of the early period following kidney transplantation. Although previously considered to be caused by tertiary hyperparathyroidism, recent evidence suggests a primary role for persistently elevated circulating levels of the phosphorus-regulating hormone, FGF23. In the setting of a healthy renal allograft, markedly increased FGF23 levels from the dialysis period induce renal phosphate wasting and inhibition of calcitriol production, which contribute to hypophosphatemia. While such tertiary FGF23 excess and resultant hypophosphatemia typically abates within the first few weeks to months post-transplant, some recipients manifest persistent renal phosphate wasting. Furthermore, increased FGF23 levels have been associated with increased risk of kidney disease progression, cardiovascular disease, and death outside of the transplant setting. Whether tertiary FGF23 excess is associated with adverse transplant outcomes is unknown. In this article, we review the physiology of FGF23, summarize its relationship with hypophosphatemia after kidney transplantation, and speculate on its potential impact on long-term outcomes of renal allograft recipients.

Persistent Glomerular Hematuria in Living Kidney Donors Confers a Risk of Progressive Kidney Disease in Donors After Heminephrectomy

Although glomerular hematuria is likely a sign of chronic kidney disease that will develop into overt nephropathy after donation, it remains unclear whether prospective donors with hematuria should be excluded. We reviewed the medical records of 242 donors who donated at our institution from 2001 to 2007 and surveyed the prevalence of hematuria pre- and postdonation. We then investigated the association of hematuria with proteinuria postdonation and trends in glomerular filtration rate. Before donation, 8.3% of 242 donors presented with persistent hematuria, a finding that was significantly associated with dysmorphic hematuria before donation. Most cases of predonation persistent hematuria persisted after donation, and the overall prevalence increased to 15.3%. During a median follow-up period of 2.3 years after donation, 8.3% developed persistent proteinuria, with incidence being significantly higher in donors having persistent hematuria with dysmorphic red blood cells (d-RBC) both before and after donation. Postdonation persistent hematuria with d-RBC was also associated with a progressive decline in renal function. These results indicate that persistent glomerular hematuria is strongly associated with a higher incidence of postdonation progressive kidney disease. Potential donors with persistent glomerular hematuria should be excluded, while those with isolated hematuria need to be evaluated with heightened caution.

Dual Renin-Angiotensin-Aldosterone System Blockade for Diabetic Kidney Disease

Blockade of the renin-angiotensin-aldosterone system (RAAS) prevents the development and progression of diabetic kidney disease (DKD). It is controversial whether the simultaneous use of two RAAS inhibitors (ie, dual RAAS blockade) further improves renal outcomes. This review examines the scientific rationale and current clinical evidence addressing the use of dual RAAS blockade to prevent and treat DKD. It is concluded that dual RAAS blockade should not be routinely applied to patients with low or moderate risk of progressive kidney disease (normoalbuminuria or microalbuminuria with preserved glomerular filtration rate). For patients with high risk of progressive kidney disease (substantial albuminuria or impaired glomerular filtration rate), clinicians should carefully weigh the potential risks and benefits of dual RAAS blockade on an individual basis until ongoing clinical trials provide further insight.

Very low but stable glomerular filtration rate after living kidney donation: is the concept of “chronic kidney disease” applicable to kidney donors?

Renal prognosis and outcome of Japanese kidney donors, who have lower preoperative glomerular filtration rate (GFR) and are generally older than their counterparts abroad, have scarcely been investigated. Here, the longitudinal changes in renal function of Japanese kidney donors were studied to clarify the prevalence and consequences of low GFR. We reviewed charts of the living kidney donors and followed renal function by estimated GFR (eGFR, ml/min/1.73 m(2)) from the time of transplantation (n = 237), until 1 (n = 162) to 3 years after donation (n = 77). Median eGFR at the time of transplant was 78.7. GFR declined by approximately 40% at 1 year after donation, and as a result, most (85%) Japanese kidney donors developed chronic kidney disease (CKD) stage 3, with a median eGFR of only 48.0. The result, that the mean change in eGFR at 1-3 years after donation showed a steady increment of 0.97 ml/min/1.73 m(2) per year, was distinct from the generally accepted notion that GFR declines with age. This upward change was seen irrespective of the absolute values of eGFR at or 1 year after donation, even including a subgroup with the lowest postoperative eGFR of <40. Most Japanese donors developed CKD stage 3 after donation but without subsequent progression, at least for several years. Although CKD is in general regarded to confer a significant risk for progressive kidney disease, this notion might not apply to living kidney donors with low GFR but without the risk factors for progression.

Cost-Effectiveness of Screening and Optimal Management for Diabetes, Hypertension, and Chronic Kidney Disease: A Modeled Analysis

Chronic kidney disease is, increasingly, both a contributor to premature deaths and a financial burden to the health system, and is estimated to affect between 10% and 15% of the adult population in Western countries. Hypertension and, in particular diabetes, are significant contributors to the global burden of chronic kidney disease. Although it might increase costs, screening for, and improved management of, persons at increased risk of progressive kidney disease could improve health outcomes. We therefore sought to estimate the costs and health outcomes of alternative strategies to prevent end-stage kidney disease, compared with usual care. A Markov model comparing: 1) intensive management versus usual care for patients with suboptimally managed diabetes and hypertension; and 2) screening for and intensive treatment of diabetes, hypertension, and proteinuria versus usual care was developed. Intervention effectiveness was based on published meta-analyses and randomized controlled trial data; costs were measured from a central health-care funder perspective in 2008 Australian dollars ($A), and outcomes were reported in quality-adjusted life-years (QALYs). Intensive treatment of inadequately controlled diabetes was both less costly (an average lifetime saving of $A133) and more effective (with an additional 0.075 QALYs per patients) than conventional management. Intensive management of hypertension had an incremental cost-effectiveness ratio (ICER) $A2588 per QALY gained. Treating all known diabetics with angiotensin-converting enzyme (ACE) inhibitors was both less costly (an average lifetime saving of $A825 per patient) and more effective than current treatment (resulting in 0.124 additional QALYs per patient). Primary care screening for 50- to 69-year-olds plus intensive treatment of diabetes had an ICER of $A13,781 per QALY gained. Primary care screening for hypertension (between ages 50 and 69 years) plus intensive blood pressure management had an ICER of $A491 per QALY gained. Primary care screening for proteinuria (between ages 50 and 69 years) combined with prescription of an ACE inhibitor for all persons showing proteinuria and all known diabetics had an ICER of $A4793 per QALY gained. Strategies combining primary care screening of 50- to 69-year-olds for proteinuria, diabetes, and hypertension followed by the routine use of ACE inhibitors, and optimal treatment of diabetes and hypertension, respectively, have the potential to reduce death and end-stage kidney disease and are likely to represent good value for money.

Dual blockade of the renin-angiotensin system: are two better than one?

The beneficial effects of blood pressure-lowering treatments on the risks of major cardiovascular events are well established [1]. Interruption of the renin–angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) has been shown to be an effective strategy for lowering blood pressure. Randomized trials have shown that ACEi can lower blood pressure by an average of 5/2 mmHg and reduce the risks of cardiovascular events and cardiovascular mortality by ∼20% (and total mortality by 10%) [2–6]. ARBs produce similar reductions in blood pressure and vascular events (although fewer patients have received them in randomized trials) [7–9]. Further, RAS blockade has been reliably shown to reduce the risk of kidney disease progression [10–15]. A meta-analysis of ACEi and ARB monotherapy in diabetic nephropathy demonstrated reductions in end-stage renal disease (ESRD) of around one-quarter for both treatments [16]. Similarly, an individual patient data meta-analysis of ACEi in non-diabetic kidney disease showed a relative risk reduction of 31% (95% CI 5–49%). The major trials of ACEi or ARB monotherapy in various patient populations are summarized in Table 1. As shown in Table 1, among patients at a low risk of renal progression ESRD occurs rarely, and only after many years or even decades. This probably explains the lack of renal benefit reported in large general population trials and meta-analyses of such trials [17–19]. Furthermore, there is some evidence that even the relative benefit might depend on baseline risk, making it even less likely that any true benefit could be detected in existing trials [10]. Whether the observed benefits of RAS blockade are only mediatedbytheirbloodpressure-loweringeffectorwhether other effects also play a role remains controversial; there is some evidence that interruption of the RAS provides more benefit than would simply be expected by the degree of blood pressure reduction alone [5,7,20]. It has been suggested that incomplete blockade of the RAS with ACEi or ARB monotherapy can cause a phenomenon called ‘aldosterone escape’, in which the lack of negative feedback from end-products of the RAS causes a reactive increase in renin and consequent increases in angiotensin I and II concentrations which overwhelm the pharmacological blockade [21]. Dual blockade would therefore be attractive as ACEi and ARB inhibit the RAS at different steps. However, there is continuing uncertainty about the balance of benefits and harms of dual RAS blockade, both in terms of cardiovascular risk and progression of kidney disease. This question will be discussed here in the context of recent evidence from randomized controlled trials.

Exploration of anaemia as a progression factor in African Americans with cardiovascular disease

Despite the higher incidence of end-stage renal disease (ESRD) among African Americans, whites in the USA have a higher prevalence of chronic kidney disease. This may be due, in part, to faster progression to ESRD among African Americans. Anaemia is associated with a risk of kidney disease progression and is more prevalent among African Americans. The purpose of this study is to determine if anaemia is associated with progression to ESRD differently according to race. A retrospective cohort study of Cooperative Cardiovascular Project data for 87 693 Medicare beneficiaries >or=65 years old and ESRD free admitted to 4047 hospitals with acute myocardial infarction between February 1994 and June 1995 was conducted. Follow-up was collected through June 2004 for ESRD and mortality. Among 87 693 patients, 7.0% were African Americans and 50.1% females. African Americans had a higher prevalence of anaemia than whites (40.2% versus 26.7%, respectively; P < 0.001). Lower haematocrit was associated with higher ESRD rates after adjustment, and the association of haematocrit with ESRD did not vary according to race (P = 0.19). This association was strongest at the lowest baseline kidney function (GFR <15) with hazard ratios increasing 7-fold as haematocrit decreased from >or= 42% to <28%. In a nationally representative sample of patients with cardiovascular disease, anaemia was associated equally among African Americans and whites with an increased risk of ESRD.

African Ancestry, Socioeconomic Status, and Kidney Function in Elderly African Americans

Kidney disease is a major public health problem in the United States that affects African Americans disproportionately. The relative contribution of environmental and genetic factors to the increased burden of kidney disease among African Americans is unknown. The associations of genetic African ancestry and socioeconomic status with kidney function were studied cross-sectionally and longitudinally among 736 community-dwelling African Americans who were aged >65 yr and participating in the Cardiovascular Health Study. Genetic African ancestry was determined by genotyping 24 biallelic ancestry-informative markers and combining this information statistically to generate an estimate of ancestry for each individual. Kidney function was evaluated by cystatin C and estimated GFR (eGFR) using the Modification of Diet in Renal Disease equation. Longitudinal changes in serum creatinine and eGFR were estimated using baseline and follow-up values. In cross-sectional analyses, there was no association between genetic African ancestry and either measure of kidney function (P = 0.36 for cystatin C and 0.68 for eGFR). African ancestry was not associated with change in serum creatinine > or =0.05 mg/dl per yr (odds ratio [OR] 0.94; 95% confidence interval [CI] 0.83 to 1.06) or with change in eGFR > or =3 ml/min per 1.73 m(2) per yr (OR 1.02; 95% CI 0.92 to 1.13). In contrast, self reported African-American race was strongly associated with increased risk for kidney disease progression compared with white individuals for change in creatinine (OR 1.77; 95% CI 1.33 to 2.36) and for change in eGFR (OR 3.21; 95% CI 2.54 to 4.06). Among self-identified African Americans, low income (< US dollars 8000/yr) was strongly associated with prevalent kidney dysfunction by cystatin C >1.29 g/dl (adjusted OR 2.7; 95% CI 1.0 to 7.5) or by eGFR <60 ml/min per 1.73 m(2) (adjusted OR 3.2; 95% CI 1.1 to 9.4) compared with those with incomes >US dollars 35,000/yr. Alleles that are known to be present more frequently in the African ancestral group were not associated with kidney dysfunction or kidney disease progression. Rather, kidney dysfunction in elderly African Americans seems more attributable to differences in environmental and social factors.

Obesity Is Associated With Family History of ESRD in Incident Dialysis Patients

Obesity is an established risk factor for chronic kidney disease and aggregates in families. The objective of this study is to examine the relationship between obesity and family history of end-stage renal disease (ESRD). Data were collected from 25,883 incident patients with ESRD in US ESRD Network 6 (Georgia, North Carolina, and South Carolina) dialysis clinics between 1995 and 2003. Family history is defined as a first- or second-degree relative with ESRD. Body mass index (BMI) at dialysis therapy initiation was classified as underweight (BMI < 18.5 kg/m2), normal (BMI, 18.5 to <25 kg/m2), overweight (BMI, 25 to < 30 kg/m2), obese (BMI, 30 to <35 kg/m2), or morbidly obese (BMI > or = 35 kg/m2). Twenty-three percent of patients reported a family history of ESRD. Of patients reporting a family history of ESRD, 5.5% were underweight, 32.5% had normal BMI, 28.0% were overweight, 17.3% were obese, and 16.7% were morbidly obese. After controlling for age, race, sex, primary cause of ESRD, history of diabetes, history of hypertension, and estimated glomerular filtration rate at dialysis therapy initiation, reported family history of ESRD was associated with being overweight (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.08 to 1.26), obese (OR, 1.25; 95% CI, 1.14 to 1.37), and morbidly obese (OR, 1.40; 95% CI, 1.27 to 1.55). Obesity at dialysis therapy initiation was associated independently with reported family history of ESRD. This finding suggests that behavioral factors, adiposity-related genes, and gene-by-BMI interaction may contribute to familial risk for ESRD. This finding also suggests that management of obesity may be even more important for patients with a family history of ESRD than for the general population.

Lessons Learned from Recent Hypertension Trials about Kidney Disease

This article reviews BP trials with primary or secondary cardiovascular (CV) or renal end points. It focuses on how results of recent trials have influenced guidelines and clinical practice with specific reference to two issues: ( 1 ) Achievement of goal BP in patients with chronic kidney disease and ( 2 ) emerging data on the importance of decreasing proteinuria to prevent CV events and slow kidney disease progression. Each study is evaluated on its strengths and weaknesses as well as extrapolation of findings to the general population. The tenants of this article are that the baseline level of proteinuria and the magnitude of proteinuria reduction are important determinants of renal outcome in addition to lowering BP and should be consider in all future trials. Second, comparing trials of people with different stages of nephropathy and unknown or differing levels of proteinuria is limited in generalizing the CV or renal outcome to a more global population. As a preamble to this article, two observations are noteworthy: First, use of antihypertensive therapy in those with stage 3 nephropathy, i.e. , GFR of <60 ml/min, will not slow the rate of decline in kidney function to the same extent as in patients with normal kidney function (stage 1). Studies to address the aforementioned questions will not be performed, however, because of low event rates, relatively higher numbers of participants, and longer duration of follow-up, hence, higher cost than currently completed studies. Thus, we are faced with extrapolating from studies to clinical practice that may not be very appropriate. Second, observations from a number of clinical studies suggest that both risk for kidney disease progression as well as CV events may be inversely related to the level of kidney function and directly related to the amount of proteinuria (macroalbuminuria), defined as >300 mg/d of protein (1– …

Value of urinary excretion of microalbumin in predicting glomerular lesions in children with isolated microscopic hematuria

Urinary microalbumin excretion was assessed in 76 children with asymptomatic microscopic hematuria in whom the presence of proteinuria, hypertension, reduced renal function, hypercalciuria, urinary tract infection or structural abnormality of the urinary tract had been excluded. All children underwent a percutaneous kidney biopsy to determine whether microalbumin excretion can be used as a marker to predict the source of hematuria. Microalbumin excretion was considered normal if the urinary ratio of microalbumin to creatinine (MA/Cr ug/mg) was < or =30. Twenty-two (29%) had microalbuminuria (MA/Cr 96+/-30 microg/mg) and 54 (71%) had normal albumin excretion (MA/Cr 13+/-2 microg/mg). Of those with normoalbuminuria, 38 (70%) had normal renal tissue, 15 (28%) thin glomerular basement membrane (TGBM) disease and 1 (2%) IgA nephropathy. In contrast, 20 (91%) of those with microalbuminuria had IgA nephropathy and 2 (9%) had TGBM disease. The mean urinary MA/Cr ratio for all IgA children was 89+/-32 microg/mg higher compared with a value for the children with TGBM disease (14 +/-3 microg/mg, P <0.001) or children whose renal biopsy appeared normal (11+/-2 microg/mg, P <0.001). Statistical analysis revealed no significant differences between the mean MA/Cr ug/mg ratio for children with TGBM disease and those with normal glomerular findings. Fourteen of the 20 children with IgA nephropathy who also had microalbuminuria were treated with an angiotensin-converting enzyme (ACE) inhibitor. Over a mean follow-up of 51 months, none developed overt proteinuia; hematuria resolved and microalbuminuria returned to normal in eight (57%) during therapy with the ACE-inhibitor. In contrast, hematuria persisted and prtoteinuria developed in the other untreated children. None of the children with TGBM disease developed overt proteinuria after a mean of 51 months. Hematuria was persistent in children with TGBM disease, but often resolved in those whose biopsies were completely normal. These data suggest that determination of urinary microalbumin excretion is warranted in the routine examination of children with isolated microscopic hematuria. Routine screening for microalbuminuria may help to identify a subgroup of patients with IgA nephropathy who are at high risk for progressive kidney disease and need more intensive therapy and closer follow-up.

Book Review

The Kidney and Hypertension Edited by George L. Bakris 233 pages . New York, NY ; Martin Dunitz ; 2004 $99.95 . ISBN 841842702 The rates of end-stage renal disease have been at epidemic levels for decades in the United States. The disparities associated with kidney disease are very significant, with African Americans being five times more likely to develop end-stage renal disease. Most alarming are the increasing disease rates, such that medicine will not be able to keep pace with the $80,000-plus annual costs for dialysis. Hypertension is a major factor associated with the risk of kidney disease progression, and it is essential that clinicians understand the blood pressure (BP)—kidney relationship and its impact on adverse health outcomes. Complicating the transfusion of the information from research to practice are the multiple aspects of the hypertension–kidney disease relationship and the changing risk profiles of the population. Bakris has edited a comprehensive multiauthored book that seeks to inform residents, fellows, and junior faculty of the current clinical concepts regarding hypertension and kidney disease. The text addresses the appropriate measurement of BP, hypertension detection, understanding of risk associated with elevated BP, mechanisms of disease, and hypertension treatment strategies based on evidence-based medicine. Specific emphasis and focus are dedicated to the issues of salt retention, action of the renin-angiotensin system, overactivity of the sympathetic nervous system, renal artery stenosis, and the resistant nature of hypertension in patients with renal disease. The book has three major sections. The first section deals with assessment, epidemiology, BP measurement, microalbuminuria, proteinuria, systolic BP, and secondary hypertension. The second section focuses on general treatment with special considerations for risk reduction, BP treatment goals, the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, treatment of elevated lipids, and hypertension urgencies. The third section addresses the treatment of high-risk patients, including patients with diabetes, African Americans and South and East Asians, pregnant patients with hypertension, children with hypertension, and BP in dialysis patients. The book has the characteristics inherit to many multiple-author texts. In particular, writing styles and relevance vary by author. The number of references included at the end of each chapter range from 9 to 74. As with many such publications, the time needed for coordinating the writing assignments, edits, rewrites, and synthesis to one document seems to have delayed the publication such that current relevant references are not included. In the case of this book, several citations refer to the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI), rather than the current JNC 7 guidelines. On the other hand the text is well indexed and structured, demonstrating an extensive review process by the editor. The book is easy to read and follow. Sections and topics of special interest to the reader are quickly identified and located. The book offers a useful resource for the intended audience, i.e., residents, fellows, and junior faculty who need to understand the impact and clinical considerations of the hypertension–kidney relationship in the patient population and, most importantly, the need for early diagnosis and aggressive treatment of hypertension to successfully reduce the population burden of kidney disease.—Daniel T. Lackland, DrPH, Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston, SC

Proteinuria and hypertensive nephrosclerosis in African Americans

Proteinuria is a known risk factor for both renal disease progression and cardiovascular morbidity and mortality in hypertensive populations. African Americans are among the highest risk groups for development of renal disease in the setting of hypertension and suffer a disproportionate burden of end-stage renal disease attributed to hypertension. Population-based studies indicate that African Americans have higher rates of albuminuria compared to non-African Americans in part due to higher rates of hypertension and diabetes in African Americans as compared to non-Hispanic whites for example. The African American Study of Kidney Disease and Hypertension (AASK) Trial was a prospective long-term clinical trial that examined the effect of aggressive blood pressure lowering versus usual blood pressure lowering in three different classes of antihypertensives on renal outcomes in approximately 1200 African Americans with hypertensive nephrosclerosis. Two thirds of trial participants had < 300 mg protein, and one third had > or = 300 mg of protein in a 24-hour urine specimen at baseline. Those with > 300 mg protein excretion compared to those with < 300 mg protein excretion at baseline had more rapid decline in renal function and ESRD events. Moreover, lower levels of proteinuria than previously thought may be important for identifying those at higher risk for kidney disease progression. The AASK cohort study, a follow-up to the trial, is now underway. The longer term follow-up will provide new insights into proteinuria and other risk factors for progression of kidney disease in hypertensive nephrosclerosis.

Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis.

Angiotensin-converting enzyme (ACE) inhibitors reduce blood pressure and urine protein excretion and slow the progression of chronic kidney disease. To determine the levels of blood pressure and urine protein excretion associated with the lowest risk for progression of chronic kidney disease during antihypertensive therapy with and without ACE inhibitors. 11 randomized, controlled trials comparing the efficacy of antihypertensive regimens with or without ACE inhibitors for patients with predominantly nondiabetic kidney disease. MEDLINE database search for English-language studies published between 1977 and 1999. Data on 1860 nondiabetic patients were pooled in a patient-level meta-analysis. Progression of kidney disease was defined as a doubling of baseline serum creatinine level or onset of kidney failure. Multivariable regression analysis was performed to assess the association of systolic and diastolic blood pressure and urine protein excretion with kidney disease progression at 22 610 patient visits. Mean duration of follow-up was 2.2 years. Kidney disease progression was documented in 311 patients. Systolic blood pressure of 110 to 129 mm Hg and urine protein excretion less than 2.0 g/d were associated with the lowest risk for kidney disease progression. Angiotensin-converting enzyme inhibitors remained beneficial after adjustment for blood pressure and urine protein excretion (relative risk, 0.67 [95% CI, 0.53 to 0.84]). The increased risk for kidney progression at higher systolic blood pressure levels was greater in patients with urine protein excretion greater than 1.0 g/d (P < 0.006). Although reverse causation cannot be excluded with certainty, a systolic blood pressure goal between 110 and 129 mm Hg may be beneficial in patients with urine protein excretion greater than 1.0 g/d. Systolic blood pressure less than 110 mm Hg may be associated with a higher risk for kidney disease progression.

Preparing the patient for renal replacement therapy

PREVIEWThe increasing number of patients at risk for progressive kidney disease in the United States demands a collaborative approach to providing care for patients with this condition. A team-based initiative is particularly important as patients prepare for renal replacement therapy (RRT). In this article, Drs Bolton and Owen discuss specific aspects of RRT preparation, including management of blood pressure, treatment of anemia and phosphorus retention, dietary modifications, vascular access considerations, and control of lipid levels to reduce cardiovascular risk.