Association between gene polymorphisms of the components of the renin-angiotensin-aldosteron system, graft function, and the prevalence of hypertension, anemia, and erythrocytosis after kidney transplantation.

INTRODUCTION: Genetic predisposition, including polymorphisms of the renin-angiotensin system (RAS) genes, are among the potential factors that may affect the occurrence of hypertension, anemia, or erythrocytosis as well as transplanted kidney function. However, the association of the RAS genes polymorphism and the kidney transplant outcomes is controversial. The aim of this study was to analyze the association between polymorphic variants of the angiotensin-converting enzyme (insertion/deletion [I/D]), angiotensinogen (M235T), and angiotensin II receptor type 1 (A1166C) genes, and the early and long-term kidney graft outcomes, as well as the prevalence of hypertension, anemia and erythrocytosis after kidney transplantation. PATIENTS AND METHODS: We included 331 consecutive kidney transplant patients performed between 1998 and 2003. Of the total, 87.9% of patients completed a 5-year follow-up. Subjects were genotyped for the I/D, M235T, and A1166C polymorphisms. RESULTS: None of the examined polymorphism affected early or long-term graft function or was associated with hypertension before or after kidney transplantation. There was no significant difference in genotype distribution between patients with and without posttransplant erythrocytosis. However, posttransplant anemia (PTA) seemed to be significantly more common among kidney recipients with TT and MT than MM angiotensinogen genotypes (35.7% vs 20.7%; P=.03). The T allele was associated with the risk of development of PTA (odds ratio, 2.12; 95% confidence interval, 1.12-3.99; P=.02). CONCLUSION: Our results do not support the hypothesis that polymorphism of the genes coding RAS components may by an independent risk factor for the development of interstitial fibrosis/tubular atrophy, posttransplant hypertension, or PTE. Further studies are necessary to investigate the association between angiotensinogen M235T genotypes and PTA.

Comparative long-term efficacy and tolerability of pitavastatin 4 mg and atorvastatin 20-40 mg in patients with type 2 diabetes mellitus and combined (mixed) dyslipidaemia.

AIM: To compare the long-term efficacy and safety of pitavastatin with atorvastatin in patients with type 2 diabetes and combined (mixed) dyslipidaemia. METHODS: Randomised, double-blind, active-controlled, multinational non-inferiority study. Patients were randomised 2 : 1 to pitavastatin 4 mg (n = 279) or atorvastatin 20 mg (n = 139) daily for 12 weeks. Patients completing the core study could continue on pitavastatin 4 mg (n = 141) or atorvastatin 20 mg (n = 64) [40 mg (n = 7) if lipid targets not reached by week 8] for a further 44 weeks (extension study). The primary efficacy variable was the change in low-density lipoprotein cholesterol (LDL-C). RESULTS: Reductions in LDL-C were not significantly different at week 12 between the pitavastatin (-41%) and atorvastatin (-43%) groups. Attainment of National Cholesterol Education Program and European Atherosclerosis Society targets for LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) was similarly high for both treatment groups. Changes in secondary lipid variables (e.g. HDL-C, apolipoprotein B and triglycerides) were similar between treatments. Post hoc analysis showed that adjusted mean treatment differences for pitavastatin vs. atorvastatin were within the non-inferiority margin at weeks 16 (+0.11%; 95% confidence interval (CI), -5.23 to 5.44) and 44 (-0.02%; 95% CI, -5.46 to 5.41) of the extension study. Both treatments were well tolerated; atorvastatin increased fasting blood glucose from baseline (+7.2%; p < 0.05), whereas pitavastatin had no significant effect (+2.1%). CONCLUSIONS: Reductions in LDL-C and changes in other lipids were not significantly different in patients treated with pitavastatin 4 mg or atorvastatin 20 or 40 mg. Pitavastatin may, however, have a more favourable effect on the glycaemic status.

Comparison of manual steering and steering via joystick of a flexible rhino endoscope.

Flexible endoscopes are used in ENT surgery for examination tasks in cases wherever rigid endoscopes are unsuitable to reach certain positions in the nasal cavity. Until today they are steered by hand and no robotized system has been put into clinical practice. One qualification a robot manipulator system has to fulfill to be accepted is not to create new disadvantages compared to the conventional method in surgery. An important factor is the time needed to steer the new system compared to the time needed to steer the conventional system. In this article a robot manipulator system and an experiment are presented to compare the particular times test persons need to perform a certain task. This approach offers the possibility to benchmark the developed robot manipulator system and future systems for flexible rhino endoscopes.

An age-related decrease in factor V Leiden frequency among Polish subjects.

Factor V Leiden (G1691A FV mutation) is a widely acknowledged risk factor of deep vein thrombosis, including pulmonary embolism as the most serious complication. However, its high prevalence of ~5%in the Caucasian population might be related to an unknown evolutionary advantage. It might exert a beneficial effect on the carrier, e.g. protecting women from excessive bleeding during labour or allowing increased survival in severe sepsis or with other inflammatory diseases. The aim of our study was to verify or contradict the hypothesis of a favourable association between the A allele (A1691) and longevity in the Polish population. For this purpose, the G1691A mutation was analyzed by PCR-RFLP in 1016 Poles: 400 neonates (187 female and 312 male), 184 healthy adults (129 female and 55 male), and 432 long-lived individuals (age ≥95 years: 343 women and 89 men). Frequencies of G1691A carriers and the A1691 allele in long-lived individuals (0.2% and 0.1%, respectively) were significantly lower than in neonates (4.2% and 2.2%, respectively) and adults (3.3% and 1.6%). The frequency of the G1691A factor V Leiden mutation decreased with age, which indicates a shorter survival time among A1691 allele carriers in the Polish population.

Quality of life among diabetic and non-diabetic patients on maintenance haemodialysis.

AIMS: To compare the quality of life of end stage renal disease (ESRD) diabetic and non-diabetic patients undergoing chronic haemodialysis. METHODS: A case-control study of 54 diabetic and 60 non-diabetic patients undergoing maintenance haemodialysis. All subjects completed the Kidney Disease Quality of Life Short Form (KDQOL-SF) version 1.3 questionnaire as well as the SF-36 Health Survey (SF-36). RESULTS: When compared to the control non-diabetic group, physical health was significantly impaired in diabetic dialysis patients (P<0.005) and staff encouragement was significantly worse (P<0.05). In both groups, all other compounds of the SF-46 and variables related to kidney disease were similar. CONCLUSIONS: To improve diabetic haemodialysis patients' quality of life, physical activity should be incorporated to the routine dialysis care and health care professionals should support them more intensively.

Practical guidance on intensification of insulin therapy with BIAsp 30: a consensus statement.

BACKGROUND: Basal insulin and premix insulin are commonly prescribed first-line insulin therapies for patients failing to maintain glycaemic control on oral therapy. When control on these insulins starts to drift, premix analogues, such as biphasic insulin aspart 30/70 (BIAsp 30), are a simple and effective tool for intensification as they can be injected up to three-times daily (TID). However, at present, international recommendations for intensification of insulin therapy using premix analogues are limited and specific guidance on dosing is not available for many scenarios. METHODS: In October 2008, an international expert panel met to review the current guidelines for insulin intensification with BIAsp 30 in patients with type 2 diabetes, with the aim of developing practical guidance for general and specialist practitioners. RESULTS: Simple treatment algorithms have been developed for (i) patients on basal insulin (human or analogue) once daily or twice daily (BID) who need intensification to BIAsp 30 BID, and (ii) patients on BIAsp 30 once daily or BID who can be intensified to BIAsp 30 BID or TID. As well as these algorithms, specific guidance has been provided on dose transfer (from basal insulin to BIAsp 30), dose split (when intensifying from once daily to BID), and combination oral therapies. In addition, a guide to dose titration is included. CONCLUSIONS: The guidelines presented here should enable general or specialist practitioners to use BIAsp 30 to intensify the insulin therapy of patients failing on basal insulin or BIAsp 30 once or twice daily.

Intensification to biphasic insulin aspart 30/70 (BIAsp 30, NovoMix 30) can improve glycaemic control in patients treated with basal insulins: a subgroup analysis of the IMPROVE observational study.

AIMS: The international IMPROVE observational study investigated the safety profile and effectiveness of biphasic insulin aspart 30/70 (BIAsp 30) in the routine treatment of patients with type 2 diabetes. We present analyses for the subgroup of patients who switched from basal insulin to BIAsp 30. METHODS: Patients in routine care who started insulin therapy with or switched to BIAsp 30 from existing insulin regimens were eligible for this 26-week study. This analysis includes only patients previously treated with basal insulin. Outcomes including adverse events, hypoglycaemic events and glycaemic profile were recorded from patients' notes, recall and diaries. RESULTS: Of the 748 patients included (age 59.7+/-11.8 years, diabetes duration 11.4+/-7.3 years, baseline HbA1c 9.1+/-1.6%), 497 were previously using human neutral protamine Hagedorn (NPH) insulin and 245 analogue basal insulin. Overall, major and minor hypoglycaemia rates decreased from baseline to final visit (major: 0.171 to 0.011; minor: 9.70 to 5.89 events/patient-year) and were similar between the subgroups. HbA1c and fasting blood glucose were significantly reduced from baseline (NPH prestudy: -1.6%, -2.4 mmol/l; analogue basal prestudy: -1.8%, -2.4 mmol/l), as was postprandial blood glucose, with 33.8% of patients achieving the HbA1c target < 7% without hypoglycaemia. Insulin dose increased slightly from prestudy (0.33+/-0.21 U/kg), baseline (0.40+/-0.20 U/kg) to final visit (0.52+/-0.26 U/kg); most patients (76%) followed a twice-daily regimen at final visit. Body weight did not change significantly and treatment satisfaction increased. CONCLUSIONS: Patients with type 2 diabetes inadequately controlled on basal insulins may improve their glycaemic control by intensification to BIAsp 30 therapy.

Spine bone mineral density in subjects after renal transplantation compared with end-stage renal failure and healthy subjects.

The aim of the study was to assess spine bone mineral density in 160 dialyzed subjects with end-stage renal failure, 81 patients after renal transplantation, and 148 controls. Spine bone mineral density [g/cm (2)] was measured by Lunar DPX-L (USA). Data analyses were performed using Statistica for Windows. In gender subgroups Z-score were significantly lower after transplantation than in controls (p<0.001), but not in subjects on dialysis. The mean value of Z-score in subjects after transplantation was significantly lower than in dialyzed patients. Z-score both in transplanted and dialyzed males were significantly lower than in females. Duration of dialysis, time since transplantation, and cumulative dose of steroids did not associate with values of spine bone mineral density (except for the negative association with dialysis duration time in males). In patients after transplantation, multiple stepwise regression analysis of spine bone mineral density and age, body size, parathormone, duration of dialysis, time after transplantation, and cumulative dose of steroids after transplantation have shown negative role of steroids use and positive role of parathormone and bone mass in males. Spine bone mineral density in dialyzed subjects was not decreased as compared with controls while the aggravation in skeletal status was observed after renal transplantation.

Safety and effectiveness of biphasic insulin aspart 30/70 (NovoMix 30) when switching from human premix insulin in patients with type 2 diabetes: subgroup analysis from the 6-month IMPROVE observational study.

AIMS: IMPROVE is an open-label, multinational, non-randomised, 26-week observational study designed to evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in routine clinical practice. Here, we report data for patients switching to BIAsp 30 from human premixed insulin. METHODS: Patients (n = 3856) with type 2 diabetes previously receiving human premixed insulin with or without oral antidiabetic drugs were eligible for inclusion. Demographic data, efficacy end-points (HbA(1c), fasting blood glucose and postprandial blood glucose) and safety end-points (serious adverse drug reactions, hypoglycaemia and adverse events) were collected at baseline and final visit. A subgroup analysis of mean dose change was also undertaken. RESULTS: Switching patients to BIAsp 30 resulted in significant improvements in glycaemic control combined with a reduced risk of hypoglycaemia. Patients who reached the HbA(1c) target (< 7%) had shorter diabetes duration, lower HbA(1c) at baseline and needed less insulin. Over 30% of patients were able to reach this target without experiencing hypoglycaemia over the 26-week period. Compared with asymmetric dose switching, unit-for-unit switching resulted in the highest proportion of patients reaching HbA(1c) target and incurred the least amount of dose titration. CONCLUSIONS: A unit-for-unit switch is the most effective as well as the simplest approach when transferring patients from biphasic human insulin 30 to BIAsp 30.

Initiating insulin therapy with, or switching existing insulin therapy to, biphasic insulin aspart 30/70 (NovoMix 30) in routine care: safety and effectiveness in patients with type 2 diabetes in the IMPROVE observational study.

AIMS: The IMPROVE observational study evaluated the safety profile and effectiveness of biphasic insulin aspart 30/70 (BIAsp 30) in patients with type 2 diabetes in routine practice in 11 countries. METHODS: Patients who initiated insulin therapy with, or switched existing insulin therapy to, BIAsp 30 in routine care were eligible for this 26-week, non-interventional observational study. Data on adverse events, hypoglycaemia and glycaemic parameters were obtained from patients' diaries and medical notes. Questionnaire-based patient treatment satisfaction was also measured. We report global results and, uniquely for a diabetes observational study, country-specific data. RESULTS: A total of 52,419 patients were enrolled from three prestudy treatment groups: no pharmaceutical therapy (n = 8966, diabetes duration 2.0 years, baseline HbA1c 9.9%), oral antidiabetic drugs (OADs) only (n = 33,797, diabetes duration 7.4 years, baseline HbA1c 9.2%) and insulin +/- OADs (n = 9568, diabetes duration 10.4 years, baseline HbA1c 9.3%). At final visit, HbA1c, fasting and postprandial blood glucose were significantly reduced from baseline in all subgroups (no pharmaceutical therapy: -3.1%, -5.9 and -9.0 mmol/l, respectively; OADs-only: -2.1%, -4.1 and -6.1 mmol/l; insulin +/- OADs: -2.0%, -3.3 and -5.1 mmol/l). Major hypoglycaemia rates decreased in all subgroups; minor hypoglycaemia increased in the insulin-naïve groups. There was no mean weight gain across subgroups. Across all countries, glycaemic parameters and major hypoglycaemia were reduced; weight increases were seen in some countries. Treatment satisfaction increased in all subgroups and countries following BIAsp 30 therapy. CONCLUSIONS: Initiating insulin with, or switching insulin therapy to, BIAsp 30 in routine care resulted in improved glycaemic control, reduced major hypoglycaemia and greater treatment satisfaction.

The IMPROVE study--a multinational, observational study in type 2 diabetes: baseline characteristics from eight national cohorts.

AIMS: The IMPROVE study is a multinational, open-label, non-randomised, 26-week observational study assessing the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) treatment in type 2 diabetes in routine clinical practice. The principal aims of this report were to characterise the baseline population and physicians' treatment decisions. METHODS: Patients with type 2 diabetes who required insulin and whose physician had decided to initiate BIAsp 30 were eligible. At baseline, demographic data and detailed medical histories were collected and physicians recorded their reasons for starting BIAsp 30, the glycaemic targets set and the regimens chosen. RESULTS: Data from 51,286 patients were included in analyses. Baseline glycaemic control was poor in all eight countries in the present analysis and in all prestudy treatment groups [no therapy, oral antidiabetic drugs (OADs) only, insulin with or without OADs], and the rates of vascular complications were high. Although the management of each of the three main measures of glycaemic control were key reasons for starting BIAsp 30, target-setting for postprandial glucose levels was variable. A twice-daily regimen was used to start BIAsp 30 therapy for 80% or more of patients. CONCLUSIONS: The IMPROVE baseline data reaffirm the global nature of poor glycaemic control in type 2 diabetes and echo the concerns that initiation of therapy, particularly insulin, is commonly delayed in clinical practice. Although postprandial glucose control was a key driver for physicians' choice of BIAsp 30, this was not consistently reflected in the targets set.

Quantitative ultrasound of phalanges of adults with end-stage renal disease or who have undergone renal transplantation.

In patients with end-stage renal disease (ESRD), bone disturbances are common. The aim of this study was to compare the bone mineral status in patients with ESRD, in patients post renal transplantation and in healthy controls. The groups were composed of 218 males and 126 females (ESRD), 43 males and 23 females (renal transplantation) and 614 males and 927 females (healthy controls). Skeletal status was evaluated by quantitative ultrasound measurements of the phalanges using a DBM 1200 (IGEA, Carpi, Italy), which measures the amplitude-dependent speed of sound (Ad-SoS) in m/s. Data analyses were performed with Statistica 6 for Windows (StatSoft, Inc., Tulsa, OK, USA). The Z-scores in gender subgroups were significantly lower in patients undergoing dialysis and after transplantation than in controls (p<0.00001). The Z-scores did not differ between gender subgroups after transplantation and the Z-scores of dialyzed males were significantly better than in females (p<0.00001). The mean value of Z-scores in patients after transplantation was significantly lower than in all patients with ESRD (p<0.05) and in males (p<0.01). The duration of dialysis negatively influenced the Ad-SoS; however, the time elapsed since transplantation did not. The cumulative corticosteroid dose did not correlate with skeletal variables. In conclusion, patients with ESRD treated with hemodialysis and postrenal transplantation patients, across both genders, were observed to have skeletal disturbances.

Quantitative ultrasound measurements in diabetic and nondiabetic patients with end-stage renal disease.

The aim of the study was to assess skeletal status in diabetic and nondiabetic subjects with end-stage renal disease (ESRD). One hundred twenty-three patients with ESRD (57 patients with diabetes: 9 type 1 and 48 type 2) and 66 nondiabetic patients were evaluated. Control group comprised 1541 subjects (614 males and 927 females). Diabetes and/or renal insufficiency was the only reason of bone disease and, in control group, no factors known to influence bone metabolism (chronic diseases or prolonged medications) were noted. Skeletal status was evaluated by quantitative ultrasound measurements at the hand phalanges using DBM 1200 (IGEA, Carpi, Italy), which measures amplitude-dependent speed of sound (Ad-SoS [m/s]). Because of some differences in mean age in subgroups of patients and controls, comparisons were performed using values of Z-score. In all diabetic patients, Z-score was significantly higher compared with nondiabetics (p < 0.05). In all type 1 diabetes patients, Z-score was significantly lower than in all nondiabetic patients (p < 0.05) and in patients with type 2 diabetes (p < 0.001). Z-score was also significantly lower in type 2 diabetics than in nondiabetic females (p < 0.00001) but did not differ in males. Comparisons between Z-scores in controls and patients showed that Z-score in nondiabetic females was significantly lower than in female controls (p < 0.000001), and in nondiabetic males--diabetic type 2 males as well as females--Z-score did not differ vs. results in adequate control group. Z-score was significantly lower in patients with diabetes type 1 vs. all controls (p < 0.001). Correlation analysis showed in all nondiabetic patients that Z-score was negatively affected by duration time of dialysis (r = -0.37, p < 0.01) and parathyroid hormone (PTH) serum level (r = -0.35, p < 0.01). In patients with type 1 diabetes, only PTH influenced significantly Z-score (r = -0.76, p < 0.05) and, in patients with type 2 diabetes, no significant correlations were obtained. Subjects with type 1 diabetes seemed to be sensitive for skeletal disturbances in a course of renal insufficiency, whereas subjects with type 2 diabetes did not show such skeletal pathology as shown by ultrasound measurements at hand phalanges.

Five weeks of treatment with the GLP-1 analogue liraglutide improves glycaemic control and lowers body weight in subjects with type 2 diabetes.

AIMS: Effects of the long acting GLP-1 analogue--liraglutide in subjects with type 2 diabetes. METHODS: 144 type 2 diabetic subjects on metformin treatment (1000 mg BID) were randomised to 5 weeks of treatment (double-blind) with metformin plus liraglutide, liraglutide or metformin, or metformin plus glimepiride (open label). The dose of liraglutide was increased weekly from 0.5 to 2 mg OD. RESULTS: Liraglutide added to metformin monotherapy was associated with a significant reduction in fasting serum glucose (FSG) (-3.9 mM -4.9; -2.9) (primary objective), and HbA1c levels (-0.8% -1.2; -0.4). Furthermore, liraglutide in combination with metformin vs. metformin plus glimepiride significantly reduced FSG (-1.2 mM -2.2; -0.2). In addition, body weight was significantly lower in the metformin plus liraglutide vs. the metformin plus glimepiride group (-2.9 kg -3.6; -2.1). There were no biochemically confirmed episodes of hypoglycaemia with liraglutide treatment. Nausea was the most frequently reported adverse event following liraglutide therapy, it was transient in nature, and led to withdrawal of only 4% of the subjects. CONCLUSIONS: Using a weekly dose-titration liraglutide is well tolerated up to 2 mg daily. While liraglutide caused transient gastrointestinal side effects, this rarely interfered with continuing treatment. An improvement in FSG over that in control groups was seen for liraglutide as an add-on to metformin. In the latter case, body weight was reduced in comparison to metformin plus glimepiride. Liraglutide is a promising drug for the treatment of type 2 diabetes.

Transmission of G-protein beta3 subunit C825T alleles to offspring affected with end-stage renal disease.

BACKGROUND: Results of epidemiological studies have suggested that a hereditary predisposition to the development of chronic renal failure exists, and that such predisposition might be independent from underlying etiology of kidney disease. On the other hand, high blood pressure contributes substantially to a faster rate of progression of renal damage, regardless of underlying etiology of kidney disease. In this study we tested whether GNB3 C825T polymorphism, previously reported to be associated with hypertension, contributes to predisposition to end-stage renal disease (ESRD). METHODS: GNB3 polymorphism was genotyped in 247 family trios: offspring affected with ESRD and both parents, and transmission/disequilibrium test was used to establish the allele-phenotype association. Among the examined offspring, 47 patients had ESRD in the course of type 1 diabetes and diabetic nephropathy, 120 had primary glomerulonephritis and 80 had interstitial nephritis. We observed no significant differences between the GNB3 C and T allele transmission from heterozygous parents to affected offspring. RESULTS: In the overall group of examined patients, the C:T allele transmission (%) was 48:52, while in patients with diabetic nephropathy, chronic glomerulonephritis and chronic interstitial nephritis the transmission was (%) 50:50, 48:52 and 48:52, respectively. CONCLUSION: The results of our study suggest that GNB3 C825T polymorphism does not contribute substantially to the increased risk of the development of ESRD.

Human SA gene Pst1 polymorphism and chronic renal failure: results of the family-based study.

BACKGROUND: Because of the heterogeneous aetiology of kidney diseases, interactions between multiple genetic and environmental factors are thought to be involved in the process of progression to end-stage renal disease (ESRD). Raised blood pressure remains a well-established, independent risk factor for a more rapid decline of renal function in various kidney diseases. The aim of the study was to investigate the role of the human SA gene Pst1 polymorphism in the development and/or progression of chronic renal failure (CRF). METHODS: This polymorphism was genotyped in a group of 247 family trios (offspring affected with end-stage renal disease, and both parents): 120 with primary chronic glomerulonephritis, 80 with interstitial nephritis, and 47 with diabetic nephropathy. Transmission/disequilibrium test (TDT) was used to evaluate allele transmission from heterozygous parents to affected offspring. RESULTS: SA gene Pst1 allele transmission did not differ from random proportion of 50:50, with no significant variation in the slope of reciprocal serum creatinine over time between patients with SA Pst1 A1A1, A1A2, and A2A2 genotypes. In addition, no impact of this marker on the rate of progression of CRF in the course of diabetes mellitus, interstitial nephritis, and chronic glomerular nephritis was shown. CONCLUSION: Results of the study suggest no major role of SA gene polymorphism in promoting renal damage. However, the limited numbers of patients having both parents alive included in the analysis might have resulted in insufficient power to detect a minor impact of this polymorphism, especially if such effect is confined to a certain aetiology of CRF.

Angiotensin I-converting enzyme gene insertion/deletion and angiotensinogen M235T polymorphisms: risk of chronic renal failure. End-Stage Renal Disease Study Group.

BACKGROUND: Chronic renal failure (CRF) is a complex phenotype that results from an underlying kidney disease and superimposing environmental and genetic factors. The aim of our study was to evaluate the role of polymorphisms in the genes encoding for components of the renin-angiotensin system (RAS) in the development and/or progression of CRF. METHODS: Two hundred forty-seven family trios (patients with CRF and both parents; 120 with primary chronic glomerulonephritis, 80 with interstitial nephritis, and 47 with type 1 diabetes with nephropathy) were examined, and transmission/disequilibrium test (TDT) was used to evaluate allele transmission from heterozygous parents to affected offspring. RESULTS: The D allele of the angiotensin I-converting enzyme (ACE) gene insertion/deletion polymorphism was transmitted significantly more frequently than expected for no association among all examined trios and in the subgroup of patients with interstitial nephritis. The angiotensinogen 235T allele was transmitted significantly more frequently to patients with CRF than expected for no association, but the effect was seen only in patients with interstitial nephritis. The presence of the DD or ID genotype was associated with a faster rate of decline of renal function, which was not observed for the angiotensinogen M235T polymorphism. For chymase gene and angiotensin II receptor type 1 gene, allele transmission did not deviate significantly from a random proportion of 50:50%. CONCLUSIONS: The results of this study suggest that ACE gene insertion/deletion and angiotensinogen M235T polymorphisms contribute to the increased risk for the development of CRF, but the magnitude of the effect within subsets of patients with specific etiologies of CRF must be evaluated further.