Association of habitual coffee consumption and kidney function: A prospective analysis in the Rotterdam Study.

BACKGROUND & AIMS: Population-based studies have suggested a protective effect of coffee against development of chronic kidney disease (CKD), possibly through coffee's anti-inflammatory and antioxidant compounds. Studies on coffee and kidney function decline in the general population are scarce. We studied associations of habitual coffee consumption with repeated assessments of estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR). METHODS: We used data from 7,914 participants of the population-based Rotterdam Study. Baseline coffee consumption data (cups/day) were obtained from home interviews and validated food frequency questionnaires (1997-2008). Repeated assessments of eGFR (ml/min per 1.73 m2, 1997-2014) were calculated according to the creatinine-based CKD Epidemiology Collaboration equation of 2012. Repeated assessments of urinary albumin and creatinine were used to estimate ACR (mg/g, 2006-2014). Data were analyzed by applying linear mixed models, adjusted for sociodemographic, lifestyle and dietary factors, and cardiovascular disease risk factors. Predefined subgroup analyses were performed stratified by CKD risk factors. RESULTS: Participants' mean (SD) baseline age was 66 (10) years, 57% were women and median [IQR] coffee consumption was 3.0 [2.0, 5.0] cups/day. Those drinking more coffee were more likely to smoke, and to have type 2 diabetes (T2D) and obesity. Mean eGFR was 79 (15) ml/min per 1.73 m2. In the total study population, coffee was not associated with longitudinal eGFR during a median of 5.4 years of follow-up (ß = 0.04 ml/min per 1.73 m2 per one cup/day [95% CI: -0.10,0.18]). However, among those aged >70 years, one additional coffee cup/day was associated with on average 0.84 (0.51,1.18) ml/min per 1.73 m2 higher longitudinal eGFR. Among obese participants this estimate was 0.32 (0.01,0.63). A protective trend was also observed among former smokers (0.17 [-0.03,0.39]) and those with T2D (0.42 [-0.05,0.88]). Coffee was not associated with longitudinal ACR (0.01 mg/ml [-0.01,0.02]). CONCLUSION: While coffee was not associated with eGFR and ACR in the total population, more coffee consumption was associated with higher longitudinal eGFR among those at higher risk for CKD, i.e., among those aged 70+ and obese participants. These findings require confirmation in other prospective cohort studies.

Relationship of several serum folate forms with kidney function and albuminuria: cross-sectional data from the National Health and Nutrition Examination Surveys (NHANES) 2011-2018.

We aim to examine the relation of several folate forms (5-methyltetrahydrofolate (5-mTHF), unmetabolised folic acid (UMFA) and MeFox) with kidney function and albuminuria, which remained uncertain. The cross-sectional study was conducted in 18 757 participants from National Health and Nutrition Examination Survey 2011-2018. The kidney outcomes were reduced estimated glomerular filtration rate (eGFR) (<60 ml/min/1·73 m2), microalbuminuria (albumin:creatinine ratio (ACR) of 30-299 mg/g) and macroalbuminuria (ACR ≥ 300 mg/g). Overall, there were significant inverse associations between serum 5-mTHF and kidney outcomes with significant lower prevalence of reduced eGFR (OR, 0·71; 95 % CI: 0·57, 0·87) and macroalbuminuria (OR, 0·65; 95 % CI: 0·46, 0·91) in participants in quartiles 3-4 (v. quartiles 1-2; both Pfor trend across quartiles <0·05). In contrast, there were significant positive relationship between serum UMFA and kidney outcomes with significant higher prevalence of reduced eGFR in participants in quartiles 2-4 (v. quartile 1; OR, 2·12; 95 % CI: 1·45, 3·12; Pfor trend <0·001) and higher prevalence of macroalbuminuria in participants in quartile 4 (v. quartiles 1-3; OR, 1·46; 95 % CI: 1·06, 2·01; Pfor trend <0·001). However, there was no significant associations of 5-mTHF and UMFA with microalbuminuria. In addition, there were significant positive relationships of serum MeFox with reduced eGFR, microalbuminuria and macroalbuminuria (all Pfor trend <0·01). In conclusion, higher 5-mTHF level, along with lower UMFA and MeFox level, was associated with lower prevalence of kidney outcomes, which may help counsel future clinical trials and nutritional guidelines regarding the folate supplement.

Blood lead, vitamin D status, and albuminuria in patients with type 2 diabetes.

Environmental lead exposure has been linked with reduced kidney function. However, evidence about its role in diabetic kidney damage, especially when considering the nutritional status of vitamin D, is sparse. In this observational study, we investigated the association between low-level lead exposure and urinary albumin-to-creatinine ratio (UACR) and assessed potential impact of vitamin D among 4033 diabetic patients in Shanghai, China. Whole blood lead was measured by graphite furnace atomic absorption spectrometry. Serum 25-hydroxyvitamin D [25(OH)D] was tested using a chemiluminescence immunoassay. The associations of blood lead with UACR and albuminuria, defined as UACR ≥30 mg/g, according to 25(OH)D levels were analyzed using linear and Poisson regression models. A doubling of blood lead level was associated with a 10.7% higher UACR (95% CI, 6.19%-15.5%) in diabetic patients with 25(OH)D < 50 nmol/L, whereas the association was attenuated toward null (2.03%; 95% CI, -5.18% to 9.78%) in those with 25(OH)D ≥ 50 nmol/L. Similarly, the risk ratios of prevalent albuminuria per doubling of blood lead level between the two groups were 1.09 (95% CI, 1.03-1.15) and 0.99 (95% CI, 0.86-1.14), respectively. Joint analysis demonstrated that a combination of high blood lead and low 25(OH)D corresponded to significantly higher UACR. Among diabetic patients with 25(OH)D < 50 nmol/L, the increment of UACR relative to blood lead was more remarkable in those with reduced estimated glomerular filtration rate (<60 mL/min/1.73 m2). These results suggested that higher blood lead levels were associated with increased urinary albumin excretion in diabetic patients with vitamin D deficiency. Further prospective studies are needed to validate our findings and to determine whether vitamin D supplementation yields a benefit.

Coffee Consumption and Kidney Function: A Mendelian Randomization Study.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality worldwide, with limited strategies for prevention and treatment. Coffee is a complex mixture of chemicals, and consumption has been associated with mostly beneficial health outcomes. This work aimed to determine the impact of coffee consumption on kidney function. STUDY DESIGN: Genome-wide association study (GWAS) and Mendelian randomization. SETTING & PARTICIPANTS: UK Biobank baseline data were used for a coffee consumption GWAS and included 227,666 participants. CKDGen Consortium data were used for kidney outcomes and included 133,814 participants (12,385 cases of CKD) of mostly European ancestry across various countries. EXPOSURE: Coffee consumption. OUTCOMES: Estimated glomerular filtration rate (eGFR), CKD GFR categories 3 to 5 (G3-G5; eGFR<60mL/min/1.73m2), and albuminuria. ANALYTICAL APPROACH: GWAS to identify single-nucleotide polymorphisms (SNPs) associated with coffee consumption in UK Biobank and use of those SNPs in Mendelian randomization analyses of coffee consumption and kidney outcomes in CKDGen. RESULTS: 2,126 SNPs were associated with coffee consumption (P<5×10-8), 25 of which were independent and available in CKDGen. Drinking an extra cup of coffee per day conferred a protective effect against CKD G3-G5 (OR, 0.84; 95% CI, 0.72-0.98; P=0.03) and albuminuria (OR, 0.81; 95% CI, 0.67-0.97; P=0.02). An extra cup was also associated with higher eGFR (ß=0.022; P=1.6×10-6) after removal of 3 SNPs responsible for significant heterogeneity (Cochran Q P = 3.5×10-15). LIMITATIONS: Assays used to measure creatinine and albumin varied between studies that contributed data and a sex-specific definition was used for albuminuria rather than KDIGO guideline recommendations. CONCLUSIONS: This study provides evidence of a beneficial effect of coffee on kidney function. Given widespread coffee consumption and limited interventions to prevent CKD incidence and progression, this could have significant implications for global public health in view of the increasing burden of CKD worldwide.

Metabolic Changes and Diabetes Microvascular Complications 5 Years After Obesity Surgery.

BACKGROUND: Obesity surgery has pronounced effects on metabolic profile of patients with type 2 diabetes mellitus (T2DM); however, reports on long-term remission rates based on the standardised and holistic criteria by the International Diabetes Federation (IDF) and effects on T2DM microvascular complications are scarce in the literature. In this retrospective clinical trial, our objectives were to assess these variables 5 years after surgery. METHODS: Clinical data and direct measurements of renal and retinal damage were collected prospectively and analysed retrospectively for 82 patients with T2DM who underwent obesity surgery and were followed up for 5 years. RESULTS: The cohort of 82 patients with T2DM that were followed up 5 years after obesity surgery was predominantly female (71%) with a median age of 51 years, weight of 133.5 kg, BMI of 46.8 kg/m2 and pre-operative duration of T2DM of 8 years; 6% of patients had diet-controlled T2DM, 57% were on non-insulin treatment and 37% were on insulin treatment pre-operatively. Of the total 82 patients, 59 patients underwent Roux-en-Y gastric bypass, 15 sleeve gastrectomy and 8 patients underwent gastric band operations. At 5 years, 5% and 15% patients achieved optimisation and improvement of the metabolic state based on the IDF criteria respectively. Surgery was associated with almost halving of the albumin-creatinine ratio in 22 patients with pre-existing albuminuria (follow-up data available for 64 patients) and an overall stabilisation of retinopathy in 24 patients with retinal images available at 5 years. CONCLUSION: Whilst the findings on microvascular complications are encouraging, the rates of metabolic remission were lower than expected and raise the need for validated protocols to assist clinicians in managing these patients more aggressively post-operatively to achieve optimum cardio-metabolic risk factor control and hopefully further reduction in microvascular and macrovascular complications.

Non-Traditional Risk Factors of Albuminuria in the Pediatric Population: A Scoping Review.

The presence of albumin in urine has been used for more than four decades as a marker of renal and cardiovascular damage. Most of the information on this marker is related to adults. The prevalence of albuminuria in the pediatric population has been reported as being 2.2-12.8% in some countries. Most research in this field is related to albuminuria and diseases, such as diabetes and hypertension. Using the methodology described by Arksey and O'Malley in 2005, a scoping review was carried out to show that the presence of albumin in urine in the pediatric population might be associated with environmental, demographic, congenital, infectious, and non-infectious factors. The information collected is supported by 74 references present in PubMed. The results reveal the multiple causes associated with albuminuria in the pediatric population. This information can be very useful for clinical practice by adding knowledge about albuminuria behavior in children.

[Urinary iodine concentration in adult patients with type 1 diabetes mellitus]. / Jodurie u nemocných s diabetes mellitus 1. typu Vztahy k vybraným parametrum charakterizujícím diabetický syndrom.

INTRODUCTION: In patients with type 1 and 2 diabetes mellitus only rare data concerning the status of iodine supplementation and impact of possible iodine deficiency is available. AIM: To get basic information about (a) state of supply with iodine in patients with type 1 diabetes mellitus (DM1T), (b) the difference from non-diabetic population, (c) possible association of iodine saturation with some clinical and laboratory features of the diabetic syndrome, including the state of thyroid gland. SUBJECTS AND METHODS: We examined 54 men and 51 women treated with DM1T in a cross-sectional study. Age: median 42 years (25th quartil 31, 75th quartil 55), DM1T duration: 18 years (13, 23), BMI: 25.9 (23.3, 29.7), HbA1c: 61 mmol/mol (51, 71), creatinine: 71 µmol/l (61, 83), micro-albuminuria 4.3 µg/min (1.9, 11.8), TSH: 1.77 mIU/l (1.12, 2.80). The iodine saturation was evaluated using iodine concentration in a sample of first morning urine. RESULTS: Urinary iodine concentration in the whole group: median 152 µg/l, 25th quartile 117 µg/l, 75th quartile 219 µg/l. More than 50 % of the urinary iodine samples fell within range of optimal saturation (100-200 µg/l), 13 % within insufficient saturation (< 100 µg/l), 35 % of the samples showed increased saturation (> 200 µg/l), in which 2/3 were men. Using multiple regression analysis we found significant positive association of urinary iodine concentration and male gender, body weight, stature, and serum creatinine. No relation between urinary iodine and clinical and laboratory features of the diabetic syndrome was found. CONCLUSIONS: Iodine saturation in examined patients with DM1T was in accordance with ICCIDD (WHO) requirements for optimal/good saturation in non-diabetic population. With respect to the chosen normal urinary iodine concentration, eg. 100, resp. 150 µg/l the features of diabetic syndrome were not different. The question whether other factors than general measures taken in the past for solution of the iodine deficiency in the Czech Republic are involved in good level of iodine saturation in patients with DM1T should be addressed in further investigations comprising larger cohorts of patients.Key words: diabetes mellitus - urinary iodine concentration.

Prevalence and determinants of chronic kidney disease in rural and urban Cameroonians: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) is a global public health problem that disproportionally affects people of African ethnicity. We assessed the prevalence and determinants of CKD and albuminuria in urban and rural adults Cameroonians. METHODS: This was a cross-sectional study of 6-month duration (February to July 2014), conducted in the health district of Dschang (Western Region of Cameroon), using a multistage cluster sampling. All adults diagnosed with albuminuria (≥ 30 mg/g) and/or decreased estimated glomerular filtration rate (eGFR) (< 60 ml/min/1.73 m(2)) were re-examined three months later. Logistic regression models were used to relate baseline characteristics with prevalent CKD. RESULTS: We included 439 participants with a mean age of 47 ± 16.1 years; with 185 (42.1 %) being men and 119 (27.1 %) being urban dwellers. There was a high prevalence of hypertension (25.5 %), diabetes (9.8 %), smoking (9.3 %), alcohol consumption (59.7 %), longstanding use of herbal medicine (90.9 %) and street medications (87.5 %), and overweight/obesity (53.3 %) which were predominant in rural area. The prevalence of CKD was 13.2 % overall, 14.1 % in rural and 10.9 % in urban participants. Equivalents figures for CKD stages G3-G4 and albuminuria were 2.5 %, 1.6 % and 5.0 %; and 12.1 %, 14.1 % and 6.7 % respectively. Existing hypertension and diabetes were associated with all outcomes. Elevated systolic blood pressure and the presence of hypertension and diabetes were the predictors of albuminuria and CKD while urban residence was associated with CKD stages G3-G4. CONCLUSION: The prevalence of CKD and albuminuria was high in this population, predominantly in rural area, and driven mostly by the commonest risk factors.

A prospective controlled study of living kidney donors: three-year follow-up.

BACKGROUND: There have been few prospective controlled studies of kidney donors. Understanding the pathophysiologic effects of kidney donation is important for judging donor safety and improving our understanding of the consequences of reduced kidney function in chronic kidney disease. STUDY DESIGN: Prospective, controlled, observational cohort study. SETTING & PARTICIPANTS: 3-year follow-up of kidney donors and paired controls suitable for donation at their donor's center. PREDICTOR: Kidney donation. OUTCOMES: Medical history, vital signs, glomerular filtration rate, and other measurements at 6, 12, 24, and 36 months after donation. RESULTS: At 36 months, 182 of 203 (89.7%) original donors and 173 of 201 (86.1%) original controls continue to participate in follow-up visits. The linear slope of the glomerular filtration rate measured by plasma iohexol clearance declined 0.36±7.55mL/min per year in 194 controls, but increased 1.47±5.02mL/min per year in 198 donors (P=0.005) between 6 and 36 months. Blood pressure was not different between donors and controls at any visit, and at 36 months, all 24-hour ambulatory blood pressure parameters were similar in 126 controls and 135 donors (mean systolic blood pressure, 120.0±11.2 [SD] vs 120.7±9.7mmHg [P=0.6]; mean diastolic blood pressure, 73.4±7.0 vs 74.5±6.5mmHg [P=0.2]). Mean arterial pressure nocturnal dipping was manifest in 11.2% ± 6.6% of controls and 11.3% ± 6.1% of donors (P=0.9). Urinary protein-creatinine and albumin-creatinine ratios were not increased in donors compared with controls. From 6 to 36 months postdonation, serum parathyroid hormone, uric acid, homocysteine, and potassium levels were higher, whereas hemoglobin levels were lower, in donors compared with controls. LIMITATIONS: Possible bias resulting from an inability to select controls screened to be as healthy as donors, short follow-up duration, and dropouts. CONCLUSIONS: Kidney donors manifest several of the findings of mild chronic kidney disease. However, at 36 months after donation, kidney function continues to improve in donors, whereas controls have expected age-related declines in function.

Vitamin D analogue therapy, cardiovascular risk and kidney function in people with Type 1 diabetes mellitus and diabetic nephropathy: a randomized trial.

AIM: To evaluate the effects of therapy with the vitamin D analogue paricalcitol on markers of cardiovascular risk and kidney function in people with Type 1 diabetes mellitus and diabetic nephropathy. METHODS: In a double-blind, randomized placebo-controlled, crossover trial, 48 participants on stable renin angiotensin aldosterone system blockade and diuretics were assigned, in random order, to 12 weeks of paricalcitol and 12 weeks of placebo therapy, separated by a 4-week washout period. Primary and secondary endpoints were changes in plasma N-terminal probrain natriuretic peptide and urinary albumin excretion rate obtained before and after each intervention. Glomerular filtration rates were estimated and measured ((51) Cr-EDTA plasma clearance glomerular filtration rate) after each intervention. RESULTS: The mean (sd) age of the participants was 57 (9) years, the baseline geometric mean (95% CI) urinary albumin excretion rate was 148 (85-259) mg/24 h, the mean (sd) HbA1c was 70 (9) mmol/mol [8.6 (3)%], the mean (sd) estimated glomerular filtration rate was 47 (15) ml/min/1.73 m(2) and the mean (sd) 24-h blood pressure was 135 (17)/74 (10) mmHg. Compared with placebo therapy, vitamin D analogue therapy had no significant effect on plasma N-terminal probrain natriuretic peptide concentration (P = 0.6), urinary albumin excretion rate was reduced by 18% (P = 0.03 for comparison), estimated glomerular filtration rate was reduced by 5 ml/min/1.73 m(2) (P < 0.001) and measured glomerular filtration rate was reduced by 1.5 ml/min/1.73 m(2) (P = 0.2). CONCLUSIONS: Paricalcitol therapy did not affect plasma N-terminal probrain natriuretic peptide concentration in people with Type 1 diabetes and diabetic nephropathy; however, the urinary albumin excretion rate was significantly lowered.

Vitamin D modulates the association of circulating insulin-like growth factor-1 with carotid artery intima-media thickness.

OBJECTIVE: Experimental evidence indicates that circulating insulin-like growth factor-1 (IGF-1) counteracts vascular aging and atherosclerosis, for which increased carotid artery intima-media thickness (IMT) is a marker. Yet, IGF-1 concentrations have been inconsistently associated with carotid IMT in epidemiological studies. Since vitamin D is also implicated in vascular protection and affects IGF-1 biology, we hypothesized that it would influence the effect of IGF-1 on IMT. METHODS: The relationship between carotid IMT and fasting serum IGF-1 was examined across strata of 25-hydroxyvitamin D [25(OH)D] in 472 participants in the Baltimore Longitudinal Study of Aging (BLSA) with well-controlled blood pressure and in 165 treatment-naive patients with essential hypertension from the Microalbuminuria: A Genoa Investigation on Complications (MAGIC) study. Moreover, the interplay between vitamin D and IGF-1 was preliminarily explored in EA.hy926 endothelial cells. RESULTS: After adjusting for age, sex, BMI, renal function, smoking, systolic blood pressure, LDL-cholesterol, glycemia, antihypertensive or lipid-lowering therapy, season, parathyroid hormone, and vitamin D supplementation, IGF-1 was significantly and negatively associated with carotid IMT only within the lowest 25(OH)D quartile (range 6.8-26 ng/mL) of the BLSA (ß -0.095, p = 0.03). Similarly, a significant negative correlation between IGF-1 and carotid IMT was found after full adjustment only in MAGIC patients with 25(OH)D concentrations below either the deficiency cut-off of 20 ng/mL (ß -0.214, p = 0.02) or 26 ng/mL (ß -0.174, p = 0.03). Vitamin D dose-dependently decreased hydrogen peroxide-induced endothelial cell oxidative stress and apoptosis, which were further inhibited by IGF in the presence of low, but not high vitamin D concentration. CONCLUSIONS: Circulating IGF-1 is vasoprotective primarily when vitamin D levels are low. Future studies should address the mechanisms of vitamin D/IGF-1 interaction.

Clinical findings associated with homozygous sickle cell disease in the Barbadian population--do we need a national SCD registry?

BACKGROUND: Comprehensive care in homozygous sickle cell disease (HbSS) entails universal neonatal screening and subsequent monitoring of identified patients, a process which has been streamlined in the neighbouring island of Jamaica. In preparation for a similar undertaking in Barbados, we have developed a database of persons with known HbSS, and have piloted processes for documenting clinical manifestations. We now present a brief clinical profile of these findings with comparisons to the Jamaican cohort. METHODS: HbSS participants were recruited from clinics and support groups. A history of select clinical symptoms was taken and blood and urine samples and echocardiograms were analysed. A re-analysis of data from a previous birth cohort was completed. RESULTS: Forty-eight persons participated (32 F/16 M); age range 10-62 yrs. 94% had a history of ever having a painful crisis. In the past year, 44% of participants had at least one crisis. There were >69 crises in 21 individuals; 61% were self-managed at home and the majority of the others were treated and discharged from hospital; few were admitted. The prevalence of chronic leg ulceration was 27%. Forty-two persons had urinalysis, 44% were diagnosed with albuminuria (urinary protein/creatinine ratio ≥30 mg/g). Thirty-two participants had echocardiography, 28% had a TRJV ≥ 2.5 m/s. Re-analysis of the incidence study revealed a sickle gene frequency (95% CI) of 2.01% (0.24 to 7.21). CONCLUSION: Although we share a common ancestry, it is thought that HbSS is less common and less severe in Barbados compared to Jamaica. The Jamaican studies reported a sickle gene frequency of 3.15 (2.81 to 3.52); the prevalence of chronic leg ulcers and albuminuria was 29.5% and 42.5% respectively. These comparisons suggest that our initial thoughts may be speculative and that HbSS may be an underestimated clinical problem in Barbados. A prospective neonatal screening programme combined with centralized, routine monitoring of HbSS morbidity and outcomes will definitively answer this question and will improve the evidence-based care and management of HbSS in Barbados.

Factors associated with CKD in the elderly and nonelderly population.

BACKGROUND AND OBJECTIVES: The risk factors for CKD in different age groups remain unknown. This community-based study aimed to identify the risk factors for CKD in elderly and nonelderly patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A multistage sampling survey for CKD was conducted in 2007 in Kaohsiung County, an area with the highest prevalence of dialysis in the world. CKD was defined as proteinuria in at least the microalbuminuric stage or an estimated GFR (eGFR) of <60 ml/min per 1.73 m(2). The factors for CKD in elderly and nonelderly patient groups were identified (with age 60 years as a cutoff value). RESULTS: The analyses included 3352 participants, of whom 687 had CKD. The weighted prevalence of CKD was 19.4% (95% confidence interval [CI], 18.0%-20.7%). Elderly patients typically presented with low eGFR and nonelderly patients, with proteinuria. Age, annual income, use of oral analgesics, metabolic syndrome, hyperuricemia, and hemoglobin were risk factors for CKD in both age groups. In elderly patients, risk factors were medical history of diabetes mellitus, CKD, stroke, and not using analgesic injection (odds ratios [95% CIs], 3.58 [2.06-6.22], 3.66 [1.58-8.43], 3.89 [1.09-13.87], 2.27 [1.21-4.17], respectively). In nonelderly patients, associated risk factors for CKD were gout, hepatitis B virus infection, and use of the Chinese herbal medicine Long Dan Xie Gan Tang (odds ratios [95% CIs], 3.15 [1.96-5.07], 1.66 [1.09-2.53], and 8.86 [1.73-45.45], respectively). CONCLUSIONS: The risk factors for CKD vary by age.

Combined inhibition of aromatase activity and dihydrotestosterone supplementation attenuates renal injury in male streptozotocin (STZ)-induced diabetic rats.

Our previous studies showed that streptozotocin (STZ)-induced diabetic male rats have increased estradiol and decreased testosterone levels that correlate with renal injury (Xu Q, Wells CC, Garman GH, Asico L, Escano CS, Maric C. Hypertension 51: 1218-1224, 2008). We further showed that either supplementing dihydrotestosterone (DHT) or inhibiting estradiol biosynthesis in these diabetic rats was only partially renoprotective (Manigrasso MB, Sawyer RT, Marbury DC, Flynn ER, Maric C. Am J Physiol Renal Physiol 301: F634-F640, 2011; Xu Q, Prabhu A, Xu S, Manigrassso MB, Maric C. Am J Physiol 297: F307-F315, 2009). The aim of this study was to test the hypothesis that the combined therapy of DHT supplementation and inhibition of estradiol synthesis would afford better renoprotection than either treatment alone. The study was performed in 12-wk-old male nondiabetic (ND), STZ-induced diabetic (D), and STZ-induced diabetic rats that received the combined therapy of 0.75 mg/day of DHT along with 0.15 mg · kg(-1) · day(-1) of an aromatase inhibitor, anastrozole (Dta), for 12 wk. Treatment with the combined therapy resulted in attenuation of albuminuria by 84%, glomerulosclerosis by 55%, and tubulointerstitial fibrosis by 62%. In addition, the combined treatment decreased the density of renal cortical CD68-positive cells by 70% and decreased protein expression of transforming growth factor-ß protein expression by 60%, collagen type IV by 65%, TNF-α by 55%, and IL-6 by 60%. We conclude that the combined treatment of DHT and blocking aromatase activity in diabetic male STZ-induced diabetic rats provides superior treatment than either treatment alone in the prevention of diabetic renal disease.

Serum phosphorus as a predictor of low-grade albuminuria in a general population without evidence of chronic kidney disease.

BACKGROUND: High levels of serum phosphorus, even within the normal range, have been associated with cardiovascular (CV) morbidity. Low-grade albuminuria (LGA) was demonstrated to be related to increased CV events in various study populations. The present study aimed to investigate the association between serum phosphorus levels and LGA in the general population. METHODS: We examined the individuals who had undergone health inspections. We evaluated the correlation between serum phosphorus and LGA in 8953 participants (mean age, 47.4 years) with estimated glomerular filtration rates (eGFRs)≥60 mL/min/1.73 m2 and urinary albumin-to-creatinine ratios (UACRs)<30 mg/g. Participants who underwent a colonoscopy were excluded. RESULTS: The mean UACR was significantly higher in the uppermost quartile group of serum phosphorus concentrations than in other quartile groups. In the multivariate regression analysis, serum phosphorus remained an independent predictor of increased UACR (B=0.610, P<0.001). Subgroup analyses showed that this association was maintained irrespective of age, gender, presence of hypertension or diabetes, body mass index and eGFR. CONCLUSIONS: In our population-based study, higher serum phosphorus was independently related to LGA in individuals without evidence of renal dysfunction. Further investigations are warranted to clarify the precise mechanism of the association between serum phosphorus and LGA.

Relationship between dietary intake and microalbuminuria: findings from the Takahata study.

BACKGROUND: Although several studies have investigated the relationship between dietary nutrient intake and microalbuminuria, no study of an Asian population has been reported. The present study investigates the relationship between dietary intake and microalbuminuria in a general Japanese population. METHODS: We analyzed 675 men and 924 women who did not have diabetes. Participants who had a urinary albumin-to-creatinine ratio (UACR) ≥300 mg/g, who did not complete a questionnaire regarding food frequency and who did not provide complete urine measurements were excluded. Nutrient intake was assessed by validated food frequency questionnaire. Microalbuminuria was defined as UACR ≥30 mg/g. The relationship between dietary nutrient intake and microalbuminuria was examined using a multiple logistic regression model adjusted for age, total energy intake, body mass index, smoking status, systolic blood pressure and use of antihypertensive medication. RESULTS: No significant association was observed among the men. The multiple adjusted odds ratios (95% confidence interval) of having microalbuminuria per 1 standard deviation increase in total protein (%kcal), animal protein (%kcal), animal protein (g/day), animal fat, niacin, carbohydrate and ß-cryptoxanthin among the women were 1.33 (1.07-1.66), 1.35 (1.09-1.66), 1.42 (1.08-1.88), 1.29 (1.05-1.59), 1.28 (1.04-1.57), 0.73 (0.58-0.92) and 0.76 (0.59-0.996), respectively. The multiple adjusted odds ratio (95% confidence interval) of having microalbuminuria in the highest quintile of n-3 polyunsaturated fatty acids compared with the lowest was 2.16 (1.03-4.54). CONCLUSION: Less animal protein and more ß-cryptoxanthin in the diet might help to prevent microalbuminuria. Prospective studies including controlled trials are required to confirm this conclusion.

Ethnic differences in the development of albuminuria: the DISTANCE study.

OBJECTIVES: To determine whether ethnic differences in the incidence of albuminuria are present in patients with diabetes, and to identify social, behavioral, and provider factors that explain ethnic differences. STUDY DESIGN: Survey follow-up design with a race-stratified baseline survey (2005-2006) in diabetic patients from a nonprofit, fully integrated healthcare system in Northern California. We followed the 10,596 respondents (30% whites, 20% blacks, 23% Hispanics, 14% Asians, and 13% Filipinos) without evidence of prevalent albuminuria at baseline. METHODS: Incident albuminuria was defined by positive dipstick urinalysis (>1) or urine albumin to creatinine level (>30 mg/g), and confirmed with repeat testing at least 3 months later. RESULTS: The 27,292 person-years of observation yielded 981 incident albuminuria events. Agestandardized rates of albuminuria (per 1000 person-years) ranged from 13.6 (95% confidence interval [CI] 10.5-17.0) in whites to 27.8 (CI 18.2- 38.3) in blacks. In fully adjusted Cox models, the hazard ratio for blacks (1.22, 95% CI 1.09-1.38), Asians (1.35, 95% CI 1.13-1.61), and Filipinos (1.93, 95% CI 1.61-2.32), but not Hispanics, was significantly greater than it was for whites. In some cases, point estimates changed markedly from the base model when fully adjusted for potential confounders. Moreover, adjustment for an array of potentially mediating factors explained only a small proportion of the observed ethnic disparities. CONCLUSIONS: Despite uniform medical care coverage, Filipinos, blacks, and Asians with diabetes developed albuminuria at higher rates than white and Hispanic adults.

Relationship of estimated GFR and coronary artery calcification in the CRIC (Chronic Renal Insufficiency Cohort) Study.

BACKGROUND: Coronary artery calcification (CAC) is associated with increased mortality risk in the general population. Although individuals with chronic kidney disease (CKD) are at markedly increased mortality risk, the incidence, prevalence, and prognosis of CAC in CKD are not well understood. STUDY DESIGN: Cross-sectional observational study. SETTING & PARTICIPANTS: Analysis of 1,908 participants who underwent coronary calcium scanning as part of the multiethnic CRIC (Chronic Renal Insufficiency Cohort) Study. PREDICTOR: Estimated glomerular filtration rate (eGFR) computed using the Modification of Diet in Renal Disease (MDRD) Study equation, stratified by race, sex, and diabetic status. eGFR was treated as a continuous and a categorical variable compared with the reference value of >60 mL/min/1.73 m(2). MEASUREMENTS: CAC detected using computed tomography (CT) using either an Imatron C-300 electron beam computed tomography (CT) scanner or multidetector CT scanner. CAC was computed using Agatston score as a categorical variable. Analyses were performed using ordinal logistic regression. RESULTS: We found a strong and graded relationship between lower eGFR and increasing CAC. In unadjusted models, ORs increased from 1.68 (95% CI, 1.23-2.31) for eGFR of 50-59 mL/min/1.73 m(2) to 2.82 (95% CI, 2.06-3.85) for eGFR <30 mL/min/1.73 m(2). Multivariable adjustment only partially attenuated the results (OR, 1.53; 95% CI, 1.07-2.20) for eGFR <30 mL/min/1.73 m(2). LIMITATIONS: Use of eGFR rather than measured GFR. CONCLUSIONS: We showed a graded relationship between severity of CKD and CAC independent of traditional risk factors. These findings support recent guidelines that state that if vascular calcification is present, it should be considered as a complementary component to be included in the decision making required for individualizing CKD treatment.

Angiotensin II receptor blocker and long-acting calcium channel blocker combination therapy decreases urinary albumin excretion while maintaining glomerular filtration rate.

Microalbuminuria is a recognized risk factor and predictor for cardiovascular events in patients with hypertension. We analyzed changes in hypotensive effect, urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) in subjects with hypertension and microalbuminuria as a subanalysis of the results of the Nifedipine and Candesartan Combination (NICE-Combi) Study. A total of 86 subjects with essential hypertension with microalbuminuria (UAE <300 mg g(-1) creatinine) were randomly assigned in a double-blind manner to a combination therapy group (standard-dose candesartan at 8 mg per day plus controlled-release (CR) nifedipine 20 mg per day) (n=42) or an up-titrated monotherapy group (candesartan 12 mg per day) (n=44) for 8 weeks of continuous treatment after initially receiving standard-dose candesartan (8 mg per day) monotherapy for 8 weeks (initial treatment). After 8weeks, blood pressure (BP) was significantly reduced in both groups compared with at the end of initial treatment. UAE also showed a significant decrease in the combination therapy group, while there was no significant change of eGFR in either group. A significant positive correlation was seen between BP reduction and UAE after 8 weeks of double-blind treatment in both groups, whereas no significant association was found between ΔUAE and ΔeGFR in either group. These findings show that combination therapy with standard-dose candesartan and nifedipine CR is more effective than up-titrated candesartan monotherapy for reducing BP and improving UAE while maintaining eGFR, and strongly suggest that the combination of an angiotensin II receptor blocker and long-acting calcium channel blocker is beneficial in patients with hypertension and microalbuminuria.