Chronic kidney disease in type 2 diabetic patients followed-up by primary care physicians in Switzerland: prevalence and prescription of antidiabetic drugs.

QUESTION UNDER STUDY: The aim of this study was to assess the prevalence of chronic kidney disease (CKD) among type 2 diabetic patients in primary care settings in Switzerland, and to analyse the prescription of antidiabetic drugs in CKD according to the prevailing recommendations. METHODS: In this cross-sectional study, each participating physician was asked to introduce anonymously in a web database the data from up to 15 consecutive diabetic patients attending her/his office between December 2013 and June 2014. Demographic, clinical and biochemical data were analysed. CKD was classified with the KDIGO nomenclature based on estimated glomerular filtration rate (eGFR) and urinary albumin/creatinine ratio. RESULTS: A total of 1 359 patients (mean age 66.5 ± 12.4 years) were included by 109 primary care physicians. CKD stages 3a, 3b and 4 were present in 13.9%, 6.1%, and 2.4% of patients, respectively. Only 30.6% of patients had an entry for urinary albumin/creatinine ratio. Among them, 35.6% were in CKD stage A2, and 4.1% in stage A3. Despite prevailing limitations, metformin and sulfonylureas were prescribed in 53.9% and 16.5%, respectively, of patients with advanced CKD (eGFR <30 ml/min). More than a third of patients were on a dipeptidyl-peptidase-4 inhibitor across all CKD stages. Insulin use increased progressively from 26.8% in CKD stage 1-2 to 50% in stage 4. CONCLUSIONS: CKD is frequent in patients with type 2 diabetes attending Swiss primary care practices, with CKD stage 3 and 4 affecting 22.4% of cases. This emphasizes the importance of routine screening of diabetic nephropathy based on both eGFR and urinary albumin/creatinine ratio, the latter being largely underused by primary care physicians. A careful individual drug risk/benefit balance assessment is mandatory to avoid the frequently observed inappropriate prescription of antidiabetic drugs in CKD patients.

Methodology used in studies reporting chronic kidney disease prevalence : a systematic literature review.

BACKGROUND: Many publications report the prevalence of chronic kidney disease (CKD) in the general population. Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods. METHODS: For this systematic review, two researchers independently searched PubMed, MEDLINE and EMBASE to identify all original research articles that were published between 1 January 2003 and 1 November 2014 reporting the prevalence of CKD in the European adult general population. Data on study methodology and reporting of CKD prevalence results were independently extracted by two researchers. RESULTS: We identified 82 eligible publications and included 48 publications of individual studies for the data extraction. There was considerable variation in population sample selection. The majority of studies did not report the sampling frame used, and the response ranged from 10 to 87%. With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas 13% used the enzymatic assay for creatinine determination. Isotope dilution mass spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%) equations were most often used to estimate glomerular filtration rate (GFR). CKD was defined as estimated GFR (eGFR) <60 mL/min/1.73 m(2) in 92% of studies. Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was reported by sex and age strata in 54 and 50% of the studies, respectively. In publications with a primary objective of reporting CKD prevalence, 39% reported a 95% confidence interval. CONCLUSIONS: The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence. These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies, which will enhance comparability of study results.

Les maladies rénales chroniques ne sont pas toutes silencieuses [Chronic kidney diseases do not always pass unnoticed].

Kidney diseases are frequent, but most of the time, they develop unnoticed. This paucity of symptoms may lead to delayed diagnosis with important consequences on their outcome. Nevertheless, specific systemic signs such as skin lesions, joint pain or electrolytes disturbances may sometimes alert the clinician and direct the diagnosis to an underlying nephropathy. A high awareness of clinicians is warranted to recognize these red flags and diagnose these diseases early, as illustrated by two clinical cases discussed in this article.

Trabecular bone score in kidney transplant recipients.

UNLABELLED: It is uncertain whether bone mineral density (BMD) can accurately predict fracture in kidney transplant recipients. Trabecular bone score (TBS) provides information independent of BMD. Kidney transplant recipients had abnormal bone texture as measured by lumbar spine TBS, and a lower TBS was associated with incident fractures in recipients. INTRODUCTION: Trabecular bone score (TBS) is a texture measure derived from dual energy X-ray absorptiometry (DXA) lumbar spine images, providing information independent of bone mineral density. We assessed characteristics associated with TBS and fracture outcomes in kidney transplant recipients. METHODS: We included 327 kidney transplant recipients from Manitoba, Canada, who received a post-transplant DXA (median 106 days post-transplant). We matched each kidney transplant recipient (mean age 45 years, 39 % men) to three controls from the general population (matched on age, sex, and DXA date). Lumbar spine (L1-L4) DXA images were used to derive TBS. Non-traumatic incident fracture (excluding hand, foot, and craniofacial) (n = 31) was assessed during a mean follow-up of 6.6 years. We used multivariable linear regression models to test predictors of TBS, and multivariable Cox proportional hazard regression was used to estimate hazard ratios (HRs) per standard deviation decrease in TBS to express the gradient of risk. RESULTS: Compared to the general population, kidney transplant recipients had a significantly lower lumbar spine TBS (1.365 ± 0.129 versus 1.406 ± 0.125, P < 0.001). Multivariable linear regression revealed that receipt of a kidney transplant was associated with a significantly lower mean TBS compared to controls (-0.0369, 95 % confidence interval [95 % CI] -0.0537 to -0.0202). TBS was associated with fractures independent of the Fracture Risk Assessment score including BMD (adjusted HR per standard deviation decrease in TBS 1.64, 95 % CI 1.15-2.36). CONCLUSION: Kidney transplant recipients had abnormal bone texture as assessed by TBS and a lower lumbar spine TBS was associated with fractures in recipients.

Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort.

STUDY OBJECTIVES: To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). METHODS: Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. RESULTS: 8.2% of participants had mild CKD (stage 1-2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2) with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30-60 mL/min/1.73 m(2)). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. CONCLUSIONS: Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function.

In vitro effect of isoschaftoside isolated from Syngonium podophyllum on pig kidney Na+, K+-ATPase

The present study aimed to investigate the in vitro effects of isoschaftoside isolated from Syngonium podophyllum on pig kidney Na+,K+-ATPase. The Na+, K+-ATPase activity was determined by colorimetric measurement of inorganic phosphate (Pi), resulting from ATP hydrolysis. Isoschaftoside significantly decreased the renal Na+, K+-ATPase activity at the highest concentration as well as at a lower concentration. Our work suggests that isoschaftoside is a promising compound for the treatment of hypertension.

Vascular Function in Chronic Kidney Disease and in Renovascular Disease

Cardiovascular mortality is 15 to 30 times higher in patients with chronic kidney disease than in the age-adjusted general population. Even minor renal dysfunction predicts cardiovascular events and death in the general population. In patients with atherosclerotic renovascular disease the annual cardiovascular event and death rate is even higher. The abnormalities in coronary and peripheral artery function in the different stages of chronic kidney disease and in renovascular disease are still poorly understood, nor have the cardiac effects of renal artery revascularization been well characterized, although considered to be beneficial. This study was conducted to characterize myocardial perfusion and peripheral endothelial function in patients with chronic kidney disease and in patients with atherosclerotic renovascular disease. Myocardial perfusion was measured with positron emission tomography (PET) and peripheral endothelial function with brachial artery flow-mediated dilatation. It has been suggested that the poor renal outcomes after the renal artery revascularization could be due to damage in the stenotic kidney parenchyma; especially the reduction in the microvascular density, changes mainly evident at the cortical level which controls almost 80% of the total renal blood flow. This study was also performed to measure the effect of renal artery stenosis revascularization on renal perfusion in patients with renovascular disease. In order to do that a PET-based method for quantification of renal perfusion was developed. The coronary flow reserve of patients with chronic kidney disease was similar to the coronary flow reserve of healthy controls. In renovascular disease the coronary flow reserve was, however, markedly reduced. Flow-mediated dilatation of brachial artery was decreased in patients with chronic kidney disease compared to healthy controls, and even more so in patients with renovascular disease. After renal artery stenosis revascularization, coronary vascular function and renal perfusion did not improve in patients with atherosclerotic renovascular disease, but in patients with bilateral renal artery stenosis, flow-mediated dilatation improved. Chronic kidney disease does not significantly affect coronary vascular function. On the contrary, coronary vascular function was severely deteriorated in patients with atherosclerotic renovascular disease, possibly because of diffuse coronary artery disease and/or diffuse microvascular disease. The peripheral endothelial function was disturbed in patients with chronic kidney disease and even more so in patient with atherosclerotic renovascular disease. Renal artery stenosis dilatation does not seem to offer any benefits over medical treatment in patients with renovascular disease, since revascularization does not improve coronary vascular function or renal perfusion.

Viabilidade do fígado bioartificial utilizando hepatócitos humanos imunoprotegidos por macroencapsulação

OBJETIVO: O transplante de hepatócitos xenogênicos encapsulados pode ser utilizado no futuro em situações como a insuficiência hepática fulminante. Porém, observa-se perda precoce da expressão de genes hepatocitários específicos em hepatócitos humanos. O objetivo deste estudo é avaliar a influência da resposta imunológica na perda da expressão genética hepatocitária de hepatócitos humanos encapsulados e transplantados em ratos. MÉTODO: Hepatócitos humanos foram isolados de fragmentos hepáticos, encapsulados em fibras e transplantados em ratos. Nos dias 3, 7 e 14 após o transplante as fibras foram coletadas e avaliadas a morfologia por microscopia óptica e eletrônica, e a expressão dos genes por biologia molecular. O ARNm da albumina humana foi quantificado por RT-PCR e Northern blot. A resposta imunológica contra os hepatócitos foi avaliada através do ADN hepatocitário na busca de apoptose do núcleo celular e pelo aumento da expressão do CMH de classe I. RESULTADOS: Os aspectos morfológicos dos hepatócitos mantiveram-se normais até o sétimo dia após o transplante. Não se observaram células envolvidas com resposta imunológica do receptor nas fibras. Os transcritos da albumina foram detectados até D-14. Entre os dias 3 e 7 estavam em 30% em relação ao dia 0. A análise do ADN mostrou bandas preservadas sem a presença de fenômenos de apoptose nos diferentes dias. Não ocorreu aumento da expressão do CMH de classe I. CONCLUSÕES: Hepatócitos humanos encapsulados e transplantados em ratos permanecem viáveis apesar da diminuição da expressão de determinados genes. Este fenômeno, não se deve à resposta imunológica do receptor, mas ao próprio processo de isolamento celular.

Epidemiological analysis of polytrauma patients with kidney injuries in a university hospital

Objective: To analyze the characteristics of trauma patients with renal lesions treated at a university hospital in Curitiba. Methods: We conducted a retrospective, cross-sectional study guided by review of medical records of trauma victims who underwent surgical treatment. The variables analyzed were age, gender, mechanism of injury, degree of kidney damage, conduct individualized according to the degree of renal injury, associated injuries, complications and deaths. We classified lesions according to the American Association of Trauma Surgery (TSAA). Results: We analyzed 794 records and found renal lesions in 33 patients, with mean age 29.8 years, most (87.8%) being male. Penetrating trauma accounted for 84.8% of cases. The most common renal injuries were grade II (33.3%), followed by grade I (18.1%), III, IV and V. Nephrectomy treated 45.4% of injuries, 73.3% being total nephrectomy, and 45.4% by nephrorraphy. In 9% treatment was non-surgical. Only 12.1% of patients had isolated renal lesions. Complications ensued in 15.1% and mortality was 6.06%. Conclusion: The surgical approach was preferred due to penetrating trauma mechanism. We achieved low rates of complications and deaths, and neither case could be directly related to kidney damage, and there were patients with multiple lesions. In this sample, we could not observe a direct relationship between kidney damage and complications, deaths or the type of conduct employed.

Does hyperglycemia in pregnancy change fetal kidney growth?: a longitudinal prospective study

PURPOSE: To measure fetal renal volume in normoglycemic and hyperglycemic pregnancies. METHODS: A longitudinal prospective study was conducted and included 92 hyperglycemic and 339 normoglycemic pregnant women attended at the prenatal service of a hospital from Rio de Janeiro State. Ultrasound examinations were performed to estimate gestational age at baseline and the kidney volume was estimated using the prolate ellipsoid volume equation. RESULTS: Fetal kidney volume growth between normoglycemic and hyperglycemic pregnancies are significantly different. The fetal kidney volume growth in pregnancy is positively correlated with gestational age explained by these predictor equations, by group: normal renal volume = exp (6.186+0.09×gestational week); hyperglycemic renal volume = exp (6.978+0.071×gestational week) and an excessive growth pattern for hyperglycemic pregnancies may be established according to gestational age. CONCLUSION: This is important for early detection of abnormalities in pregnancy, particularly in diabetic mothers.

Serum intact parathyroid hormone levels in cats with chronic kidney disease

Chronic kidney disease (CKD) is frequently observed in cats and it is characterized as a multisystemic illness, caused by several underlying metabolic changes, and secondary renal hyperparathyroidism (SRHPT) is relatively common; usually it is associated with the progression of renal disease and poor prognosis. This study aimed at determining the frequency of SRHPT, and discussing possible mechanisms that could contribute to the development of SRHPT in cats at different stages of CKD through the evaluation of calcium and phosphorus metabolism, as well as acid-base status. Forty owned cats with CKD were included and divided into three groups, according to the stages of the disease, classified according to the International Renal Interest Society (IRIS) as Stage II (n=12), Stage III (n=22) and Stage IV (n=6). Control group was composed of 21 clinically healthy cats. Increased serum intact parathyroid hormone (iPTH) concentrations were observed in most CKD cats in all stages, and mainly in Stage IV, which hyperphosphatemia and ionized hypocalcemia were detected and associated to the cause for the development of SRHPT. In Stages II and III, however, ionized hypercalcemia was noticed suggesting that the development of SRHPT might be associated with other factors, and metabolic acidosis could be involved to the increase of serum ionized calcium. Therefore, causes for the development of SRHPT seem to be multifactorial and they must be further investigated, mainly in the early stages of CKD in cats, as hyperphosphatemia and ionized hypocalcemia could not be the only factors involved.

Effects of aluminum sulfate on delta-aminolevulinate dehydratase from kidney, brain, and liver of adult mice

The purpose of the present study was to investigate the in vitro and in vivo effects of aluminum sulfate on delta-aminolevulinic acid dehydratase (ALA-D) activity from the brain, liver and kidney of adult mice (Swiss albine). In vitro experiments showed that the aluminum sulfate concentration needed to inhibit the enzyme activity was 1.0-5.0 mM (N = 3) in brain, 4.0-5.0 mM (N = 3) in liver and 0.0-5.0 mM (N = 3) in kidney. The in vivo experiments were performed on three groups for one month: 1) control animals (N = 8); 2) animals treated with 1 g% (34 mM) sodium citrate (N = 8) and 3) animals treated with 1 g% (34 mM) sodium citrate plus 3.3 g% (49.5 mM) aluminum sulfate (N = 8). Exposure to aluminum sulfate in drinking water inhibited ALA-D activity in kidney (23.3 ± 3.7%, mean ± SEM, P<0.05 compared to control), but enhanced it in liver (31.2 ± 15.0%, mean ± SEM, P<0.05). The concentrations of aluminum in the brain, liver and kidney of adult mice were determined by graphite furnace atomic absorption spectrometry. The aluminum concentrations increased significantly in the liver (527 ± 3.9%, mean ± SEM, P<0.05) and kidney (283 ± 1.7%, mean ± SEM, P<0.05) but did not change in the brain of aluminum-exposed mice. One of the most important and striking observations was the increase in hepatic aluminum concentration in the mice treated only with 1 g% sodium citrate (34 mM) (217 ± 1.5%, mean ± SEM, P<0.05 compared to control). These results show that aluminum interferes with delta-aminolevulinate dehydratase activity in vitro and in vivo. The accumulation of this element was in the order: liver > kidney > brain. Furthermore, aluminum had only inhibitory properties in vitro, while in vivo it inhibited or stimulated the enzyme depending on the organ studied.

Effects of microcystin-LR in isolated perfused rat kidney

Microcystin is a hepatotoxic peptide which inhibits protein phosphatase types 1 and 2A. The objective of the present study was to evaluate the physiopathologic effects of microcystin-LR in isolated perfused rat kidney. Adult Wistar rats (N = 5) of both sexes (240-280 g) were utilized. Microcystin-LR (1 µg/ml) was perfused over a period of 120 min, during which samples of urine and perfusate were collected at 10-min intervals to determine the levels of inulin, sodium, potassium and osmolality. We observed a significant increase in urinary flow with a peak effect at 90 min (control (C) = 0.20 ± 0.01 and treated (T) = 0.32 ± 0.01 ml g-1 min-1, P<0.05). At 90 min there was a significant increase in perfusate pressure (C = 129.7 ± 4.81 and T = 175.0 ± 1.15 mmHg) and glomerular filtration rate (C = 0.66 ± 0.07 and T = 1.10 ± 0.04 ml g-1 min-1) and there was a significant reduction in fractional sodium tubular transport at 120 min (C = 78.6 ± 0.98 and T = 73.9 ± 0.95%). Histopathologic analysis of the perfused kidneys showed protein material in the urinary space, suggestive of renal toxicity. These data demonstrate renal vascular, glomerular and urinary effects of microcystin-LR, indicating that microcystin acts directly on the kidney by probable inhibition of protein phosphatases.

Relationship between the actions of atrial natriuretic peptide (ANP), guanylin and uroguanylin on the isolated kidney

Guanylin and uroguanylin are peptides that bind to and activate guanylate cyclase C and control salt and water transport in many epithelia in vertebrates, mimicking the action of several heat-stable bacteria enterotoxins. In the kidney, both of them have well-documented natriuretic and kaliuretic effects. Since atrial natriuretic peptide (ANP) also has a natriuretic effect mediated by cGMP, experiments were designed in the isolated perfused rat kidney to identify possible synergisms between ANP, guanylin and uroguanylin. Inulin was added to the perfusate and glomerular filtration rate (GFR) was determined at 10-min intervals. Sodium was also determined. Electrolyte dynamics were measured by the clearance formula. Guanylin (0.5 µg/ml, N = 12) or uroguanylin (0.5 µg/ml, N = 9) was added to the system after 30 min of perfusion with ANP (0.1 ng/ml). The data were compared at 30-min intervals to a control (N = 12) perfused with modified Krebs-Hanseleit solution and to experiments using guanylin and uroguanylin at the same dose (0.5 µg/ml). After previous introduction of ANP in the system, guanylin promoted a reduction in fractional sodium transport (%TNa+, P<0.05) (from 78.46 ± 0.86 to 64.62 ± 1.92, 120 min). In contrast, ANP blocked uroguanylin-induced increase in urine flow (from 0.21 ± 0.01 to 0.15 ± 0.007 ml g-1 min-1, 120 min, P<0.05) and the reduction in fractional sodium transport (from 72.04 ± 0.86 to 85.19 ± 1.48, %TNa+, at 120 min of perfusion, P<0.05). Thus, the synergism between ANP + guanylin and the antagonism between ANP + uroguanylin indicate the existence of different subtypes of receptors mediating the renal actions of guanylins.