Measured and Estimated Glomerular Filtration Rate to Evaluate Rapid Progression and Changes over Time in Autosomal Polycystic Kidney Disease: Potential Impact on Therapeutic Decision-Making.

Autosomal polycystic kidney disease (ADPKD) is the most common genetic form of kidney failure, reflecting unmet needs in management. Prescription of the only approved treatment (tolvaptan) is limited to persons with rapidly progressing ADPKD. Rapid progression may be diagnosed by assessing glomerular filtration rate (GFR) decline, usually estimated (eGFR) from equations based on serum creatinine (eGFRcr) or cystatin-C (eGFRcys). We have assessed the concordance between eGFR decline and identification of rapid progression (rapid eGFR loss), and measured GFR (mGFR) declines (rapid mGFR loss) using iohexol clearance in 140 adults with ADPKD with ≥3 mGFR and eGFRcr assessments, of which 97 also had eGFRcys assessments. The agreement between mGFR and eGFR decline was poor: mean concordance correlation coefficients (CCCs) between the method declines were low (0.661, range 0.628 to 0.713), and Bland and Altman limits of agreement between eGFR and mGFR declines were wide. CCC was lower for eGFRcys. From a practical point of view, creatinine-based formulas failed to detect rapid mGFR loss (-3 mL/min/y or faster) in around 37% of the cases. Moreover, formulas falsely indicated around 40% of the cases with moderate or stable decline as rapid progressors. The reliability of formulas in detecting real mGFR decline was lower in the non-rapid-progressors group with respect to that in rapid-progressor patients. The performance of eGFRcys and eGFRcr-cys equations was even worse. In conclusion, eGFR decline may misrepresent mGFR decline in ADPKD in a significant percentage of patients, potentially misclassifying them as progressors or non-progressors and impacting decisions of initiation of tolvaptan therapy.

Improved short-term outcomes of kidney transplants in controlled donation after the circulatory determination of death with the use of normothermic regional perfusion.

Normothermic regional perfusion (NRP) allows the in situ perfusion of organs with oxygenated blood in donation after the circulatory determination of death (DCDD). We aimed at evaluating the impact of NRP on the short-term outcomes of kidney transplants in controlled DCDD (cDCDD). This is a multicenter, nationwide, retrospective study comparing cDCDD kidneys obtained with NRP versus the standard rapid recovery (RR) technique. During 2012-2018, 2302 cDCDD adult kidney transplants were performed in Spain using NRP (n = 865) or RR (n = 1437). The study groups differed in donor and recipient age, warm, and cold ischemic time and use of ex situ machine perfusion. Transplants in the NRP group were more frequently performed in high-volume centers (≥90 transplants/year). Through matching by propensity score, two cohorts with a total of 770 patients were obtained. After the matching, no statistically significant differences were observed between the groups in terms of primary nonfunction (p = .261) and mortality at 1 year (p =  .111). However, the RR of kidneys was associated with a significantly increased odds of delayed graft function (OR 1.97 [95% CI 1.43-2.72]; p < .001) and 1-year graft loss (OR 1.77 [95% CI 1.01-3.17]; p = .034). In conclusion, compared with RR, NRP appears to improve the short-term outcomes of cDCDD kidney transplants.

Extending the Battery Life of the ZigBee Routers and Coordinator by Modifying Their Mode of Operation.

Wireless sensor networks proliferate more and more in all social scopes and sectors. Such networks are implemented in smart homes, smart cities, security systems, medical resources, agriculture, automotive industry, etc. Communication devices and sensors of such networks are powered with batteries: the enlarging of battery life is a hot research topic. We focus on wireless sensor networks based on ZigBee technology. While sleep standard operation mode is defined for end devices, it is not the case for the rest of devices (routers and Coordinator), which usually always remain in active mode. We designed a formal optimization model for maximizing the enlarging of the battery life of routers and Coordinator, allowing us to delimit practical successful conditions. It was successfully tested with a standard ZigBee datasheet comprising technical data for sensors, routers, and coordinators. It was tested in a practical wireless sensor network assembly with XBee S2C devices. We derived, from the previous model, a novel but simple protocol of communication among routers and coordinators. It was tested in different use cases. We showed that when end devices generate traffic at regular intervals, the enlarging of the battery life of routers and Coordinator was possible only under certain use cases.

Interference Effects Redress over Power-Efficient Wireless-Friendly Mesh Networks for Ubiquitous Sensor Communications across Smart Cities.

Ubiquitous sensing allows smart cities to take control of many parameters (e.g., road traffic, air or noise pollution levels, etc.). An inexpensive Wireless Mesh Network can be used as an efficient way to transport sensed data. When that mesh is autonomously powered (e.g., solar powered), it constitutes an ideal portable network system which can be deployed when needed. Nevertheless, its power consumption must be restrained to extend its operational cycle and for preserving the environment. To this end, our strategy fosters wireless interface deactivation among nodes which do not participate in any route. As we show, this contributes to a significant power saving for the mesh. Furthermore, our strategy is wireless-friendly, meaning that it gives priority to deactivation of nodes receiving (and also causing) interferences from (to) the rest of the smart city. We also show that a routing protocol can adapt to this strategy in which certain nodes deactivate their own wireless interfaces.

Spanish modified version of the palliative care outcome scale-symptoms renal: cross-cultural adaptation and validation.

BACKGROUND: Patients with chronic kidney disease (CKD) have a high symptoms burden that is related to a poor health-related quality of life (HRQoL) and high costs of care. Validated instruments may be useful for assessing the symptoms and monitoring outcomes in these patients. The Palliative care Outcome Scale-Symptoms Renal (POS-S Renal) is a patient-reported outcome measure for assessing symptoms in CKD stage 4-5. This study is the first cross-cultural adaptation and psychometric analysis of this clinical tool. The purpose of this study is to carry out a cross-cultural adaptation of the POS-S Renal for Spanish-speaking patients, and to perform an analysis of the psychometric properties of this questionnaire. METHODS: The English version of the POS-S Renal was culturally adapted and translated into Spanish using a double forward and backward method. An expert panel evaluated the content validity. The questionnaire was pilot-tested in 30 patients. A total of 200 patients with CKD stage 4-5 filled in a modified Spanish version of the POS-S Renal and the MSAS-SF. Statistical analysis to evaluate the psychometric properties of the questionnaire was carried out. RESULTS: The content validity index (CVI) was 0.97, which indicated that the content of the instrument is an adequate reflection of the symptoms in advanced CKD (ACKD). The factor analysis indicated a two-factor solution explaining 35.05% of total variance. The confirmatory factor analysis (CFA) demonstrated that the two factor model was well supported (comparative fit index = 0.98, root mean square error of approximation = 0.068). This assessment tool demonstrated a satisfactory test-retest reliability (r = 0.909 to factor 1, r = 0.695 to factor 2, r = 0.887 to total score), good internal consistency to factor 1 (α = 0.78) and moderate internal consistency to factor 2 (α = 0.56). Concurrent criterion-related validity with MSAS-SF was also demonstrated, with r = 0.860, which indicated a high degree of correlation with a validated instrument that has been used in patients with ACKD. CONCLUSIONS: The Spanish modified version of the POS-S Renal is a reliable and valid instrument that can be used to assess symptoms in Spanish patients with CKD stage 4-5.

The error of estimated GFR in predialysis care.

The error of estimated glomerular filtration rate (eGFR) and its consequences in predialysis are unknown. In this prospective multicentre study, 315 predialysis patients underwent measured GFR (mGFR) by the clearance of iohexol and eGFR by 52 formulas. Agreement between eGFR and mGFR was evaluated by concordance correlation coefficient (CCC), total deviation index (TDI) and coverage probability (CP). In a sub-analysis we assessed the impact of eGFR error on decision-making as (i) initiating dialysis, (ii) preparation for renal replacement therapy (RRT) and (iii) continuing clinical follow-up. For this sub-analysis, patients who started RRT due to clinical indications (uremia, fluid overload, etc.) were excluded. eGFR had scarce precision and accuracy in reflecting mGFR (average CCC 0.6, TDI 70% and cp 22%) both in creatinine- and cystatin-based formulas. Variations -larger than 10 ml/min- between mGFR and eGFR were frequent. The error of formulas would have suggested (a) premature preparation for RTT in 14% of stable patients evaluated by mGFR; (b) to continue clinical follow-up in 59% of subjects with indication for RTT preparation due to low GFRm and (c) to delay dialysis in all asymptomatic patients (n = 6) in whom RRT was indicated based on very low mGFR. The error of formulas in predialysis was frequent and large and may have consequences in clinical care.

Inflammation on the Waiting List Is a Risk Factor for New-Onset Prediabetes and Post-Transplant Diabetes Mellitus: A Prospective Study.

INTRODUCTION: Inflammation is a risk factor for diabetes in the general population. The role of inflammation in prediabetes or post-transplant diabetes mellitus (PTDM) is not clear. We evaluated the association between inflammatory markers in patients on the waiting list for renal transplantation and the onset of prediabetes and PTDM 12 months after transplantation. METHODS: This is a post hoc analysis of a prospective study that included nondiabetic patients on the waiting list for kidney transplantation who underwent an oral glucose tolerance test (OGTT) and were followed up to 12 months after transplantation. At this time, those patients without PTDM underwent another OGTT. At pre-transplantation, five cytokines: TNFα, IL6, IL1ß, CRP, MCP1 were determined. The association between inflammation and prediabetes/PTDM was evaluated using multiple regression models. RESULTS: 110 patients on the waiting list were enrolled: 74 had normal glucose metabolism and 36 had prediabetes or occult diabetes. At 12 months, 53 patients had normal glucose metabolism, 25 prediabetes, and 32 PTDM. In multiple regression analysis, pre-transplant inflammation was not a risk factor for prediabetes or PTDM. This was attributed to the high interrelation between obesity, prediabetes, and inflammation: about 75% of the cases had these conditions. In a sub-analysis, we analyzed only patients without prediabetes and occult diabetes on the waiting list and found that TNFα levels and BMI at pre-transplantation were independently associated with the onset of prediabetes or PTDM 1 year after transplantation. CONCLUSIONS: Pre-transplant inflammation and BMI are risk factors for prediabetes and PTDM in patients without glucose metabolism alterations.

Sodium-glucose cotransporter-2 inhibitor therapy in kidney transplant patients with type 2 or post-transplant diabetes: an observational multicentre study.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have cardioprotective and renoprotective effects. However, experience with SGLT2is in diabetic kidney transplant recipients (DKTRs) is limited. Methods: This observational multicentre study was designed to examine the efficacy and safety of SGLT2is in DKTRs. The primary outcome was adverse effects within 6 months of SGLT2i treatment. Results: Among 339 treated DKTRs, adverse effects were recorded in 26%, the most frequent (14%) being urinary tract infection (UTI). In 10%, SGLT2is were suspended mostly because of UTI. Risk factors for developing a UTI were a prior episode of UTI in the 6 months leading up to SGLT2i use {odds ratio [OR] 7.90 [confidence interval (CI) 3.63-17.21]} and female sex [OR 2.46 (CI 1.19-5.03)]. In a post hoc subgroup analysis, the incidence of UTI emerged as similar in DKTRs treated with SGLT2i for 12 months versus non-DKTRs (17.9% versus 16.7%). Between baseline and 6 months, significant reductions were observed in body weight [-2.22 kg (95% CI -2.79 to -1.65)], blood pressure, fasting glycaemia, haemoglobin A1c [-0.36% (95% CI -0.51 to -0.21)], serum uric acid [-0.44 mg/dl (95% CI -0.60 to -0.28)] and urinary protein:creatinine ratio, while serum magnesium [+0.15 mg/dl (95% CI 0.11-0.18)] and haemoglobin levels rose [+0.44 g/dl (95% CI 0.28-0.58]. These outcomes persisted in participants followed over 12 months of treatment. Conclusions: SGLT2is in kidney transplant offer benefits in terms of controlling glycaemia, weight, blood pressure, anaemia, proteinuria and serum uric acid and magnesium. UTI was the most frequent adverse effect. According to our findings, these agents should be prescribed with caution in female DKTRs and those with a history of UTI.

Renin-angiotensin system blockade and kidney transplantation: a longitudinal cohort study.

BACKGROUND: The beneficial effect of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) in kidney transplant recipients on modern immunosuppression is not yet well established. Our objective was to investigate the impact of the use of ACEI/ARB on patient and graft survival in a cohort of kidney transplant recipients. METHODS: A total of 990 patients, who received a single deceased donor kidney at our institution between 1996 and 2005, were included in this longitudinal cohort study. All-cause mortality and death-censored graft loss were the primary outcomes. We used traditional time-dependent Cox model (unweighted) and inverse-probability-of-treatment weighting of marginal structural models (weighted Cox model), controlling for time-dependent confounding by indication. RESULTS: A total of 414 patients (42%) received ACEI/ARB through the study period (median duration 14 months, interquartile range 6-40 months). ACEI/ARB use was associated with reduction of risk for mortality in the crude [hazard ratio (HR) 0.627, 95% confidence interval (CI) 0.412-0.953] and adjusted Cox analysis (HR 0.626, 95% CI 0.407-0.963). Similar results were observed after adjusting for confounding by indication (HR 0.629, 95% CI 0.407-0.973). By contrast, ACEI/ARB use was not associated with significant improvement of graft survival after kidney transplantation. CONCLUSION: ACEI/ARB prescription may be suggested as beneficial among multiple medications for reducing mortality in kidney transplant recipients, but its use was not associated with longer graft survival.

Efficacy and Safety of Eculizumab in Kidney Transplant Patients With Primary Atypical Hemolytic-Uremic Syndrome.

The atypical hemolytic-uremic syndrome (aHUS) is characterized by the triad of non-immune hemolytic anemia, thrombocytopenia, and acute renal failure. The aHUS is related to complement dysregulation; since the approval of eculizumab for this entity (a monoclonal antibody that inhibits C5 activation and blocks the formation of the membrane attack complex) the prognosis has improved. The recurrence of aHUS after kidney transplantation is frequent and implies loss of the graft in a high percentage of cases. Eculizumab prophylaxis to prevent recurrence has allowed successful kidney transplantation in this group of patients. We present a series of kidney transplant patients with chronic kidney disease secondary to aHUS and the use of eculizumab for prevention of recurrence.

Characteristics, management and outcomes of atypical haemolytic uraemic syndrome in kidney transplant patients: a retrospective national study.

BACKGROUND: Kidney transplantation (KTx) is a strong trigger for the development of either recurrent or de novo atypical haemolytic uraemic syndrome (aHUS). According to previous studies, eculizumab (ECU) is effective for prophylaxis and for treatment of recurrence. METHODS: We evaluated the experiences of Spanish patients with recurrent and de novo aHUS associated with KTx, treated or not treated with ECU. In the de novo group, we classified patients as having early de novo (during the first month) or late de novo aHUS (subsequent onset). RESULTS: We analysed 36 cases of aHUS associated with KTx. All of the 14 patients with pre-KTx diagnosis of aHUS were considered to have high or moderate risk of recurrence. Despite receiving grafts from suboptimal donors, prophylactic ECU was effective for avoiding recurrence. The drug was stopped only in two cases with low-moderate risk of recurrence and was maintained in high-risk patients with no single relapse. There were 22 de novo aHUS cases and 16 belonged to the early de novo group. The median time of onset in the late group was 3.4 years. The early group had a better response to ECU than the late group, probably due to earlier diagnosis and use of the drug. No genetic pathogenic variant was detected in de novo aHUS cases, suggesting a secondary profile of the disease. ECU was stopped in all de novo patients with no relapses. ECU was well tolerated in all cases. CONCLUSIONS: Both groups (pre-aHUS and de novo) presented different clinical profiles, management approaches and outcomes. One should consider aHUS regardless of time after KTx. Genetic studies are crucial to stratify risks of relapse and to determine necessary lengths of treatment. We suggest short ECU treatment for de novo cases without pathogenic mutation and that ECU treatment be considered pre-emptively for patients with moderate or high risk of recurrence.

Pancreas transplantation: differences in activity between Europe and the United States.

BACKGROUND: Although pancreas transplantation (PT) is the treatment of choice in selected diabetic patients, the International Pancreas Transplant Registry (IPTR) has reported important differences in activity between USA and Europe. Of all cases reported, 75% are from USA and only 23% from Europe. Therefore, an analysis of PT activity in selected European countries (SEC) and USA was performed. Materials and methods. We compared national data reports (2002-06) of deceased donors (DD) and deceased solid organ transplantation (DSOT), with special attention to PT activity from 13 SEC countries (375 million inhabitants) and USA (298 million inhabitants). RESULTS: The number of PT performed in USA was 2-fold higher than in SEC, with the annual rate >2.4 times higher in USA [5.08-4.64 versus 1.61-1.91 per million population (p.m.p.)]. DD and other DSOT activity rates were only slightly higher in USA. In SEC, important differences in PT activity rate were found between countries in the same year (0-6.21 p.m.p.) and in the same country between different years (6.21-2.47 p.m.p.), unrelated to DD or other DSOT activity rate. PT activity rate increased in SEC from 1.61 to 1.91 p.m.p. but decreased in six countries. The waiting list for PT at the end of 2006 was almost 2-fold higher in USA than in SEC. CONCLUSIONS: Differences in PT activity rate between 13 SEC countries and USA were not related to DD or other DSOT activity. Different waiting list inclusion criteria or incidence of diabetes complications may be considered in more specific studies.

[Immunosuppression for living donor renal allograft recipients]. / Inmunosupresión del receptor de donante vivo.

Living donor kidney transplantation allows immunosuppression individualization based on clinical and immunological criteria. Living donor kidney transplantation allows administration of immunosuppressive drugs days before transplantation, for a better acute rejection prevention. A 3-day course of tacrolimus and a micophenolic acid derivative is recommended. In recipients HLA-identical related to the donor, a tacrolimus-micophenolic acid régimen is recommended. Tacrolimus withdrawal after 6 months may be advisable. In all non-HLA-identical recipients, basiliximab induction is recommended, with the exception of high immunological risk patients, in whom thymoglobulin is a better option. The use of a kidney from an expanded criteria donor might imply a reduction in tacrolimus exposure since the very beginning, to optimize kidney graft function. In general, and depending on immunological risk, steroid withdrawal after the first 3 to 6 months is recommended. ABO-incompatible living donor kidney transplantation is feasible after specific immunoadsorption, gammaglobulins, a dose of rituximab and conventional immunosupression.

Carotid atheromatosis in nondiabetic renal transplant recipients: the role of prediabetic glucose homeostasis alterations.

BACKGROUND: Prediabetic glucose homeostasis alterations are important cardiovascular risk factors but their role in renal transplant recipients (RTR) has not been established. METHODS: In 172 RTRs without pretransplant or de novo diabetes, we measured carotid intima media thickness (c-IMT) and performed an oral glucose tolerance test (OGTT). RESULTS: In multivariate analysis, age, hypertension and male sex were independently associated with a c-IMT in the third tertile. A significant interaction between gender and glucose homeostasis parameters was observed. Among male RTR, those with a c-IMT in the third tertile showed significantly higher plasma glucose and HbA1c levels (5+/-0.5% vs. 5.1+/-0.5% vs. 5.5+/-0.4%; P<0.01 tertile 3 vs. 2 or 1) than those in other tertiles. Insulin action parameters were not significantly different. The odds ratio of being in the higher c-IMT tertile was 2.9 (95% CI: 1.05-8.1) per each 1% increase of HbA1c. By contrast, glucose and HbA1c levels were not significantly different between c-IMT tertiles in female RTR. However, age-adjusted insulin levels after OGTT were higher (86+/-10 vs. 51.7+/-9.4; P=0.02) and the insulin sensitivity index lower (0.8+/-0.3 vs. 0.048+/-0.03; P=0.04) among females in the third tertile as compared to the first one. CONCLUSION: Prediabetic glucose homeostasis alterations in RTRs are related to carotid atherosclerosis, although there may be gender differences in the underlying alteration.

Mineral metabolism disorders, vertebral fractures and aortic calcifications in stable kidney transplant recipients: The role of gender (EMITRAL study).

BACKGROUND AND OBJECTIVES: The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. METHOD: We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. RESULTS: Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. CONCLUSIONS: Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients.

Heart valve calcification and calcium x phosphorus product in hemodialysis patients: analysis of optimum values for its prevention.

BACKGROUND: Prevalence of valve calcification (VC) in end-stage renal disease (ESRD) patients is high and information regarding modifiable predictors is scarce. Our aim was to determine the prevalence of VC in our maintenance hemodialysis (HD) population, and the optimal Ca x P value that most accurately predicted the presence of VC after controlling for comorbidities. METHODS: This was a cross-sectional observational study of a cohort of 52 stable patients on maintenance HD for more than 12 months. Mean 12 months serum biochemical data (calcium, phosphorus, PTH, lipids) and M-mode 2D echocardiogram were used to evaluate the presence or absence of mitral and aortic VC and ventricular geometry. RESULTS: Twenty patients (38.4%) presented with VC. Patients with VC were more commonly diabetic and showed higher levels of serum phosphorus, Ca x P product, total and LDL cholesterol, and poor ventricular geometry, as compared to patients without VC. Moreover, they required higher doses of both CaCO3 and Al(OH)3. Logistic regression analysis showed that VC was independently influenced by age, Ca x P, and diabetes. ROC curves illustrated that a Ca x P>43 mg2/dL2 was the optimal value in terms of sensitivity and specificity for predicting the presence of VC in our patient population. CONCLUSION: These findings highlight the importance of applying more vigorous measures for Ca x P control.

The influence of renin-angiotensin system genotypes on the antiproteinuric response to high doses of olmesartan in non-diabetic proteinuric nephropathies.

OBJECTIVE: To assess the antiproteinuric response to multifactorial treatment based on high doses of angiotensin II receptor antagonists (ARBs) (olmesartan) in patients with non-diabetic proteinuric nephropathies, according to three renin-angiotensin system (RAS) polymorphisms: insertion/deletion of the angiotensin converting enzyme (ACE) gene, the angiotensinogen gene M235T and the angiotensin II type 1 receptor (AT1R) A1166C. MATERIAL AND METHOD: We studied 53 patients with non-diabetic proteinuric nephropathy with a mean progression time of 84.4±15 months. 41 were males (77.4%); mean age 49.7±3 years, body mass index 30±6kg/m2. All received olmesartan (40mg/12h) associated with a mean of 2.4±1.6 antihypertensive drugs for a median period of 13 months (interquartile range 7-25 months). RESULTS: Systolic blood pressure (BP) decreased from 145±14mmHg to 128±14mmHg (P<.001) and diastolic BP from 85±11mmHg to 79±7mmHg (P<.01). Pulse pressure decreased from 53.5±14mmHg to 48±12mmHg (P<.05). Proteinuria decreased from 2.74±1.6g/24h to 0.9±1g/24h (P<.001), representing a mean decrease of 67.1%. According to RAS polymorphisms, antiproteinuric response was: angiotensinogen gene polymorphism: genotype TT: 76.8%; genotype MM: 67.3%; genotype MT: 65.8%, significantly higher (P<.05) for genotype TT compared to genotypes MM and MT. Polymorphism of the ACE gene: genotype DD: 71.4%; genotype ID: 60.6%, genotype II: 34.8%, significantly higher (P<.05) for genotype DD compared to genotypes ID and II, and also (P<.05) for genotype ID compared to II. AT1R gene polymorphism: genotype AC: 85.2%; genotype CC: 73.7%; genotype AA: 62.7%; significantly higher for genotype AC (P<.05) compared to genotypes AA and CC. The differences between initial and final proteinuria for the follow-up period were significant (P<.01) for genotypic associations DD/AA, DD/MT, DD/MM, DD/TT and DD/AC, although the association with the highest antiproteinuric effect was DD/AC (89.9%, P<.05%). CONCLUSIONS: Administering high doses of olmesartan in patients with non-diabetic proteinuric nephropathy results in significant reductions in proteinuria. This decrease was independent of blood pressure control and other confounding factors. RAS polymorphisms may modulate the antiproteinuric response to treatment with ARBs.