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PubMed2006

Is early treatment of anaemia with epoetin-alpha beneficial to pre-dialysis chronic kidney disease patients? Results of a multicentre, open-label, prospective, randomized, comparative group trial.

BACKGROUND: This multicentre, open-label prospective, randomized, comparative-group study evaluated the effects of maintaining haemoglobin (Hb) in pre-dialysis chronic kidney disease (CKD) patients. METHODS: A total of 197 patients were randomized to start subcutaneous epoetin-alpha (SC-EPO; EPREX; 1000 U twice weekly) at an early stage of anaemia to maintain Hb at 11.0 +/- 1.0 g/dl (group A, n = 65), or to allow Hb to fall to < or =9.0 g/dl before starting SC-EPO (group B, n = 132) (2000 U three times weekly); and subsequently maintaining Hb at 11.0 +/- 1.0 g/dl. RESULTS: Of 132 patients randomized to group B, 55 progressed to treatment (-trigger). The study was prematurely terminated due to contraindication of the subcutaneous administration route. Mean weekly EPO doses at 1 year were 1471 U for group A; 820 U for group B; final doses were 2281 U for group A; 2099 U for group B. There was no significant difference between groups A and B with regard to left ventricular mass (-12.5 vs -9.7%; P = 0.82). In groups A and B, 48% and 52%, respectively, terminated the study because of dialysis/death, after a median of 36.3 and 27.3 months, respectively. CONCLUSION: Early intervention to correct anaemia in CKD patients did not have a significant impact on LVM, the primary efficacy variable. Time to dialysis/death was not significantly different between groups A and B.

Adolescent↗

PubMed2006

Antenatal oligohydramnios of renal origin: long-term outcome.

BACKGROUND: Prognosis of fetuses with renal oligohydramnios (ROH) is often still regarded as poor. Neonatal complications and the long-term follow-up of fetuses with ROH in two pediatric centres are described. Method. 23 fetuses (16 males, 7 females) were included as patients. Primary diseases included congenital anomalies of the kidney and urinary tract (n = 16), autosomal recessive polycystic kidney disease (n = 4) and renal tubular dysgenesis (n = 3). The analysis includes retrospective chart review. RESULTS: Seven children died (30%), the majority (n = 4, 17%) within the neonatal period due to pulmonary hypoplasia and renal insufficiency. Fourteen patients (61%) required postnatal mechanical ventilation for a median of 4 (range 1-60) days; 11 infants had an associated pneumothorax. All 16 surviving children have chronic kidney disease (CKD) at a current median age of 5.7 years (range 0.5-14.5), managed conservatively in eight patients [median glomerular filtration rate 51 (range 20-78) ml/min/1.73 m(2)]. Eight patients reached end-stage renal disease at a median age of 0.3 years (range 2 days to 8.3 years), including one patient with pre-emptive kidney transplantation. Five of the patients requiring dialysis underwent successful renal transplantation at a median age of 3.5 years (range 2.5-4). Growth was impaired in seven children requiring growth hormone treatment. Cognitive and motor development was normal in 12 (75%) of the 16 patients and showed a delay in four children, including two with associated syndromal features. CONCLUSION: ROH is not always associated with a poor prognosis and long-term outcome in survivors is encouraging. The high incidence of neonatal complications and long-term morbidity due to CKD requires a multidisciplinary management of these children.

Adolescent↗

PubMed2006

Measurement of vascular calcification using CT fistulograms.

BACKGROUND: Vascular calcification (VC), precipitated by calcium and phosphate imbalance, is a major contributor to cardiovascular disease (CVD) in chronic kidney disease (CKD). Electron-beam computed tomography (EBCT) quantitatively assesses coronary artery calcification (CAC), with VC scores predictive of atherosclerosis and cardiac events in the general and CKD population. EBCT is not readily available but spiral CT can also provide quantitative assessment of the extent of VC. CT fistulograms can be used as initial investigation for arterio-venous fistula (AVF) problems in haemodialysis (HD). The images obtained include thoracic aorta, brachio-cephalic, subclavian and common carotid arteries which allow assessment of the extent of VC in these vessels. No study to date has combined the CT fistulogram with concurrent determination of VC. METHODS: We hypothesize that a single investigation for AVF management may also provide information on VC. We retrospectively analysed CT fistulograms on 28 HD patients determining VC scores (in Hounsfield units) in AVF, subclavian and carotid arteries and aorta. We correlated these scores with patient demographics, serum markers of mineral metabolism (time averaged for the period 6 months prior to CT) and calcium-based phosphate binders. RESULTS: Patients (60.7% male) had a median age of 59 years and 46.4% were diabetic. The mean duration of dialysis was 17.5 months. CT fistulograms showed predominantly aortic (75% of patients) and subclavian (75%) calcifications, with only 21.4% having carotid VC and minimal VC at the level of AVF. Median VC scores were 619.8 (0-1481.4) for aorta and 521.7 (0-1139.6) for subclavian (scores of >400 indicate severe atherosclerotic disease), but there was no significant correlation with serum markers or duration of HD. Increasing age correlated significantly with greater VC in aortic (R = 0.53, P = 0.003) and subclavian (R = 0.40, P = 0.03) vessels, as well as with the number of VC sites involved. CAC was present in most patients (89.3%) but CAC scores were not able to be determined because of cardiac movement. CONCLUSION: Concurrent determination of the degree of calcification in certain vessels may be possible from CT studies assessing AVF structure. VC scores provided by CT fistulograms could contribute to HD patient CVD risk assessment but studies with larger patient numbers are required to determine their relevance.

Adult↗

PubMed2003

National kidney disease education program.

The National Kidney Disease Education Program (NDKEP) is a program of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health. It seeks to increase awareness of CKD among high risk groups and primary care providers. The NKDEP is a response to the rapidly escalating incidence of ESRD in the United States in the face of new treatment to prevent and mitigate CKD. The hope is that awareness will lead to action, testing, and treatment.

Female↗

PubMed2004

Development, prevention, and potential reversal of left ventricular hypertrophy in chronic kidney disease.

Although a high prevalence of left ventricular (LV) hypertrophy is recognized with increasing severity of chronic kidney disease (CKD), previously neither its progression nor its potential for prevention or reversal has been addressed adequately in this population group. A nested analysis of a 2-yr study involving 155 patients with stage 3/4 CKD, examining effects of hemoglobin change (range, 90 to 130 g/L) on LV mass in patients with (n = 46; 30%) and without (n = 105; 70%) initial LV hypertrophy, is reported. At baseline, the group with LV hypertrophy was older (P < 0.01), had higher BP (P < 0.01), had greater LV wall and cavity dimensions (P < 0.001), and had more prevalent use of antihypertensive agents (P < 0.001) but a lower hemoglobin concentration (P < 0.05) and GFR (P < 0.01). A total of 117 patients were available for assessment at 2 yr. Importantly, 57 (68%) with initial normal LV indices showed no appreciable change with time; however, 27 (32%) developed LV hypertrophy, with growth in both wall and cavity dimensions (P < 0.001). In contrast, 23 (50%) of those with initial LV hypertrophy maintained elevated LV indices, whereas 10 (22%) regressed, through wall but not cavity reduction, to within normal LV indices. Predisposing factors to maintaining or achieving normal LV mass dimensions included relative youth (P < 0.05), a lower pulse pressure (P < 0.05), and a higher GFR (P < 0.05) but not hemoglobin concentration or parathyroid hormone levels. These findings suggest that even at a relatively advanced stage of renal dysfunction, control of BP and volume, together with regulated metabolic and clinical indices, may contribute to the prevention or even reversal of LV hypertrophy in a substantial proportion of patients.

Adolescent↗

PubMed2005

Benefits of erythropoietin in renal transplantation.

Anemia is a common complication in patients with chronic kidney diseases (CKD), including transplanted patients. Recent studies have found a prevalence of anemia of about 30%, whereas less than 10% of these patients received recombinant human erythropoietin. Factors explaining this high incidence of anemia in renal transplant recipients include delayed and impaired graft function and use of drugs inhibiting the action of angiotensin II and preventing rejection. Like in CKD patients, chronic anemia may impact on the cardiovascular system and finally on the high mortality of these patients. Recent data suggest also that anemia may be a factor of progression of renal dysfunction in kidney transplant recipients. A French randomized multicenter study was designed to answer this question.

Anemia↗

PubMed2005

Endothelial functions improve with decrease in asymmetric dimethylarginine (ADMA) levels after renal transplantation.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased cardiovascular events. The relationships between the markers of inflammation and endothelial dysfunction were investigated both before and after living donor kidney transplantation. METHODS: Twenty-seven renal transplant patients were studied. Eleven patients (six male, five female) were on cyclosporine A, whereas 16 patients (nine male, seven female) were treated with tacrolimus based regimes. Twenty-seven subjects (12 males, 15 females) were studied as controls. Plasma adiponectin, high sensitive C reactive protein (hsCRP), Asymetric dimethyl arginine (ADMA) levels were studied before transplantation and on days 1, 3, 7, 14, and 28. The brachial artery flow mediated dilatation (FMD) was studied before transplantation and on the 28th day. RESULTS: Serum hsCRP and ADMA levels decreased significantly from the first posttransplantation day on each measurement (P<0.001 for all) while the decrement of plasma adiponectin started in the third day (P<0.001 for all). The FMD was lower in the patients than the control group (P<0.001) and improved significantly in the 28th day of transplantation (P<0.001). CONCLUSIONS: The results indicate that ADMA is associated with FMD in CKD both before and after kidney transplantation. Endothelial functions improve at the very beginning of the posttransplantation period with accompanying reduction in ADMA and hsCRP levels.

Adult↗

PubMed2026

Home blood pressure telemonitoring reveals race-specific patterns of target organ damage.

BACKGROUND: Racial differences in cardiac and renal target organ damage (TOD) may persist at comparable blood pressure levels. This study compared TOD in high-risk, non-African-American Black and White patients in relation to the home blood pressure (HBP). METHODS: UPRIGHT-HTM (NCT04299529) is an ongoing international trial comparing risk stratification strategies in asymptomatic patients, aged 55-75  years, with ≥5 risk factors. Patients engage in HBP telemonitoring (OMRON HEM 9210-T). After 34.7 months (median), 287 Black and 154 White patients underwent echocardiography. At baseline, their chronic kidney disease (CKD) grade was assessed by cross-classification of the race-free estimated glomerular filtration rate and albuminuria (2024 KDIGO guideline). HBP was stratified by the 2024 ESC thresholds. Linear and logistic regression models, including a race-by-HBP interaction term, were applied to assess associations with the home systolic HBP. RESULTS: The number of HBP readings was 252 215. Median systolic/diastolic HBP was 127/77 mmHg with 142 patients (32.2%) having home hypertension. Fewer Black patients received statins or combination therapy for hypertension or diabetes. Among nonhypertensive White compared to Black patients, left atrial dimensions, mitral annular s', and stroke volume had a steeper slope in relation to systolic HBP. All patients had concentric left ventricular remodeling, but only 4 Black and 13 White patients had an ejection fraction < 50%. CKD grade was worse in Black than White patients without association with HBP. CONCLUSIONS: TOD primarily affects the kidney in Black and the heart in White patients. Intensifying pharmacological treatment in sub-Saharan Africa, including antihypertensives, lipid-lowering agents, antidiabetic medications, and aspirin, should create an opportunity for improved overall cardiovascular and metabolic prevention.

Aged↗

PubMedDate not supplied

C-reactive protein and end-stage renal disease.

The significance of CRP and inflammation has increased over time, especially in the end-stage renal disease (ESRD) population. From a simple marker it now appears that CRP is an active participant in pro-atherosclerotic phenomenon including local pro-inflammatory and thrombotic events. Studies in the general population indicate the usefulness of CRP in prognostication and in monitoring response to therapy. The clinical usefulness of CRP monitoring in chronic kidney disease (CKD) and especially in ESRD deserves closer study. In the meantime, the utility of CRP measurements for monitoring and treatment is on a case-by-case basis. Management of traditional cardiovascular risk factors should be considered. In the interest of optimizing therapy it is prudent to use biocompatible membranes and ultrapure water. A careful search for infectious processes in dialysis patients is recommended, with special attention to vascular access sites, periodontitis, gastritis, and other potentially chronic or covert infections. ACE-inhibitor use should be maximized in all eligible CKD patients. The data on the use of statins in ESRD have been generally positive but await further validation. Individualized use for selected patients is probably beneficial.

Anemia↗

PubMed2007

Association of serum fetuin-A with carotid arterial stiffness.

OBJECTIVE: Fetuin-A is a circulating glycoprotein which is well characterized as an inhibitor of ectopic calcification. Vascular calcification commonly found in chronic kidney disease (CKD) patients is a predictor of cardiovascular death. Recently, several groups have demonstrated that low fetuin-A levels are associated with mortality in uraemic patients, possibly through regulation of vascular calcification. However, the physiological significance of fetuin-A in atherosclerosis remains unknown, except in specific conditions, such as vascular calcification in CKD patients. The objective of this study was to investigate the association between serum fetuin-A levels and arterial stiffness, a functional property of atherosclerosis, in healthy subjects. PATIENTS AND MEASUREMENTS: The study subjects comprised 141 healthy subjects. We measured serum fetuin-A levels and stiffness parameter beta for the common carotid artery, which was assessed by ultrasound using a phase-locked echo-tracking system. RESULTS: Simple regression analyses indicated that serum fetuin-A levels were significantly correlated with stiffness parameter beta (r = 0.200, P = 0.018). Multiple regression analyses showed that, besides age, fetuin-A (beta = 0.166, P = 0.033) independently contribute to the stiffness parameter beta (R(2) = 0.310, P < 0.0001). CONCLUSIONS: Serum fetuin-A level is associated with carotid arterial stiffness, independent of known atherogenic factors in healthy subjects.

Age Factors↗

PubMed2005

Molecular mechanisms activating muscle protein degradation in chronic kidney disease and other catabolic conditions.

Muscle atrophy is a prominent feature of chronic kidney disease (CKD) and is frequent in other catabolic conditions. Results from animal models of these conditions as well as patients indicate that atrophy is mainly owing to accelerated muscle proteolysis in the ubiquitin-proteasome (Ub-P'some) proteolytic system. The Ub-P'some system, however, rapidly degrades actin or myosin but cannot breakdown actomyosin or myofibrils. Consequently, another protease must initially cleave the complex structure of muscle. We identified caspase-3 as an initial and potentially rate-limiting proteolytic step that cleaves actomyosin/myofibrils to produce substrates degraded by the Ub-P'some system. In rodent models of CKD and other catabolic conditions, we find that caspase-3 is activated and cleaves actomyosin to actin, myosin and their fragments. This initial proteolytic step in muscle leaves a characteristic footprint, a 14-kDa actin band, providing a potential diagnostic tool to detect muscle catabolism. We also found that stimulation of caspase-3 activity depends on inhibition of IRS-1-associated phosphatidylinositol 3-kinase (PI3K) activity; inhibiting PI3K in muscle cells also leads to expression of a critical E3-ubiquitin-conjugating enzyme involved in muscle protein breakdown: atrogin-1/MAFbx. Thus, protein breakdown by caspase-3 and the ubiquitin-proteasome system in muscle are stimulated by the same signal: a low PI3K activity. These responses could yield therapeutic strategies to block muscle atrophy.

Caspase 3↗

PubMed2005

Sex, haemoglobin and kidney disease: new perspectives.

Anaemia is recognized as a common complication of chronic kidney disease with significant associated morbidity and mortality. Published data document the negative impact of anaemia on cardiovascular disease outcomes, progression of chronic kidney disease (CKD), hospitalizations, rehabilitation and quality of life, among others. Gender differences have been identified in many of these areas as well as, and importantly, in cardiovascular and chronic kidney disease outcomes. Female gender is associated with lower risk of cardiovascular morbidity and mortality as well as slower progression of chronic kidney disease. Interestingly, there are some well-described physiological adaptations to anaemia in women, which include shifting of the haemoglobin oxygen dissociation curve to reduce oxygen affinity secondary to higher levels of 2,3-diphosphoglycerate. However, the complex physiology underlying the impact of anaemia or gender on patients with chronic kidney disease is not well-characterized to date. Furthermore, there has been little examination of the potential interaction between anaemia and gender on cardiac or kidney outcomes. In this paper, we review the documented impact of anaemia and gender on outcomes, and explore the interaction of anaemia and gender in patients with CKD. We also present data that describe the potential importance of considering gender when targeting specific levels of haemoglobin. The value of a new perspective on haemoglobin and gender in kidney disease is important from both a physiological and an economical perspective.

Anemia↗

PubMed2006

Protein biomarkers associated with acute renal failure and chronic kidney disease.

Acute renal failure (ARF) as well as chronic kidney disease (CKD) are currently categorized according to serum creatinine concentrations. Serum creatinine, however, has shortcomings because of its low predictive values. The need for novel markers for the early diagnosis and prognosis of renal diseases is imminent, particularly for markers reflecting intrinsic organ injury in stages when glomerular filtration is not impaired. This review summarizes protein markers discussed in the context of ARF as well as CKD, and provides an overview on currently available discovery results following 'omics' techniques. The identified set of candidate marker proteins is discussed in their cellular and functional context. The systematic review of proteomics and genomics studies revealed 56 genes to be associated with acute or chronic kidney disease. Context analysis, i.e. correlation of biological processes and molecular functions of reported kidney markers, revealed that 15 genes on the candidate list were assigned to the most significant ontology groups: immunity and defence. Other significantly enriched groups were cell communication (14 genes), signal transduction (22 genes) and apoptosis (seven genes). Among 24 candidate protein markers, nine proteins were also identified by gene expression studies. Next generation candidate marker proteins with improved diagnostic and prognostic values for kidney diseases will be derived from whole genome scans and protemics approaches. Prospective validation still remains elusive for all proposed candidates.

Acute Kidney Injury↗

PubMed2006

An open-label study of darbepoetin alfa administered once monthly for the maintenance of haemoglobin concentrations in patients with chronic kidney disease not receiving dialysis.

OBJECTIVE: To demonstrate the efficacy and safety of once-monthly (QM) darbepoetin alfa administration in maintaining haemoglobin (Hb) 11.0-13.0 g dL(-1) in subjects with chronic kidney disease (CKD) not receiving dialysis and previously treated with darbepoetin alfa every other week (Q2W). SUBJECTS: This open-label study enrolled subjects > or =18 years of age who had glomerular filtration rate > or =15 and < or =60 mL min(-1)/1.73 m(2), had Hb 11.0-13.0 g dL(-1), and were receiving Q2W darbepoetin alfa. DESIGN: Subjects were switched to QM darbepoetin alfa therapy for 28 weeks; the QM dose was titrated to maintain Hb levels. Primary end-point: proportion of subjects maintaining Hb > or =11.0 g dL(-1) during the final 8 weeks of the study (evaluation phase). Secondary end-points: Hb concentration during evaluation, darbepoetin alfa dose during the study, adverse events, laboratory parameters, and blood pressure. RESULTS: The study enrolled 152 subjects (female 52%, white 64%). Mean Hb > or =11.0 g dL(-1) during evaluation was achieved by 76% of the 150 subjects who received at least one dose of darbepoetin alfa [95% confidence interval (CI): 68%, 83%]. Mean (SD) Hb during evaluation was 11.71 (0.92) g dL(-1). Eighty-five per cent of 129 subjects who completed the study (95% CI: 78%, 91%) had Hb > or =11.0 g dL(-1) during evaluation. The dose of darbepoetin alfa over the study period was median (95% CI) 124.4 mug (106.2, 140.0). Darbepoetin alpha administered QM was well tolerated in study subjects. CONCLUSION: Darbepoetin alpha administered QM maintained Hb in study subjects with CKD not receiving dialysis.

Administration, Oral↗

PubMed2005

Predictors of diabetic end-stage renal disease in Japan.

Diabetes mellitus (DM) has been the leading cause of incident dialysis in Japan since 1998, according to the Japanese Society for Dialysis Therapy (JSDT). In particular, the number of male DM dialysis patients is increasing. DM is becoming a worldwide epidemic in both developed and developing countries. Strategies to detect individuals at high-risk of developing CKD and end-stage renal disease (ESRD) are needed that can be implemented on a population-basis. Among the commonly measured variables, dipstick urinalysis (proteinuria, haematuria), blood pressure, serum creatinine, body mass index (BMI), and serum uric acid are significant predictors of ESRD. Recently, we evaluated the effect of DM as a risk factor of developing ESRD. DM was diagnosed when the fasting plasma glucose (FPG) was 126 mg/dL or more in participants (n = 78529) of the 1993 screening program in Okinawa. The prevalence of DM was 5.2%. The odds ratio (95% CI) of DM for developing ESRD was 3.098 (1.738-5.525, P = 0.0001) after adjusting for possible confounding variables. Early detection and treatment of DM might prevent DM-related ESRD. We examined 7125 non-DM screenees who underwent a 1-day health check between April 1997 and March 1998. They were followed-up until March 2000 to determine whether they developed DM. Over the 2 years, the cumulative incidence of DM was 2.3%, 2.9% in men and 1.3% in women. Proteinuria was the most robust predictor of the development of DM; the adjusted relative risk (95% CI) was 1.90 (1.14-3.17). Obesity, per se, is also recognized as a risk factor for developing proteinuria. The higher the BMI, the higher the risk of developing ESRD; the adjusted odds ratio (95% CI) was 1.273 (1.121-1.446, P = 0.0002) for men. Other than being overweight (BMI = 25.0 kg/m2), a smoking habit was a significant predictor of developing proteinuria. The prevalence of obesity and DM is increasing in Japan. It is possible that the impact of obesity and complications of DM are different among races and ethnicities. Public relations regarding the risk of DM and its complications are especially important in Asian countries. Asians have more fat than non-Asians, even at the same BMI levels. Knowledge of the predictors of DM-ESRD is crucial as a first step toward prevention. Consistent with this notion, initiatives on the management of CKD and ESRD were recently organized in Japan and internationally.

Asian People↗

PubMed2006

Prevention of chronic kidney disease: the next step forward!

The incidence of end stage renal disease in patients who have not experienced a classic primary renal disease is dramatically increasing. Chronic kidney disease (CKD) in these patients is due to diabetes, mostly type 2, hypertension and generalised atherosclerosis. As these patients are frequently diagnosed as having renal function impairment only in the late phase, more effort should be undertaken to diagnose them earlier, that is, at a time when renoprotective measures can still be undertaken. For that purpose, measurement of the estimated glomerular filtration rate (GFR) might be helpful. To properly interpret those measurements, however, we need to be aware of the pros and cons of the use of formulas to estimate the GFR. Most likely, a better way to detect subjects at risk of CKD in the early phase is screening by dipstick proteinuria or preferably by testing for (micro-) albuminuria. Because microalbuminuria not only indicates increased renal but also enhanced cardiovascular risk, the benefits of such screening programmes may have a much greater affect than only preventing renal disease.

Albuminuria↗

PubMed2006

Prevention programmes of progressive renal disease in developing nations.

Development of strategies for the early detection and prevention of non-communicable diseases, including kidney disease, is the only realistic strategy to avert an imminent global health and economic crisis and enhance equity in health care worldwide. In this article, we briefly examine the burden of non-communicable diseases, including diabetes, hypertension, cardiovascular disease and how chronic kidney disease (CKD) represents a key integrated element in the setting, even in developing countries. A possible explanation of the increasing number of people who have or are at risk to develop CKD in poor countries is also given. A survey of major screening and intervention programmes performed or ongoing globally is then presented, highlighting differences and hurdles of projects planned in developed or developing nations as well as in unprivileged communities in developed countries. Finally, some recommendations on future steps to implement prevention programmes in emerging worlds are provided.

Developing Countries↗

PubMedDate not supplied

Ambulatory medical care for elderly diabetics: the Fredericia survey of diabetic and fasting hyperglycaemic subjects aged 60-74 years.

The use of services from the primary health care system and hospital outpatient clinics was studied in persons aged 60-74 years. We studied 228 persons with known diabetes (KD) (52 insulin treated, 101 OHA, 66 diet, 9 untreated) and 87 with fasting hyperglycaemia (FH) and compared with sex and age matched controls (223 CKD, 82 CFH). Information on all services provided by the primary health care system during the 12 months before ascertainment was obtained from local and national registers. FH did not receive more primary care services and did not visit outpatient clinics more than controls. Two to three times more KD than controls received all kinds of services from general practice or visited outpatient clinics. No difference was seen for specialists, except for dentists and otologists who provided fewer services to KD than to CKD. Of insulin treated KD 56% had greater than or equal to 10 contacts with physicians during the year, independent of residual beta-cell function. The corresponding proportions for OHA-treated and diet treated KD were 27% and 29%. Outpatient clinics were visited by 79% of insulin treated KD (88% with high and 65% with low C-peptide secretion), 26% of OHA-treated KD and 33% of diet-treated KD. The prevalence of ischaemic heart disease, hypertension, and microalbuminuria was not increased in the KD using most primary care services.

Aged↗