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1.
Proteomics Clin Appl ; : e2000027, 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32710812

RESUMO

Urinary peptides gained significant attention as potential biomarkers especially in the context of kidney and cardiovascular disease. In this manuscript the recent literature since 2015 on urinary peptide investigation in human kidney and cardiovascular disease is reviewed. The technology most commonly used in this context is capillary electrophoresis coupled mass spectrometry, in part owed to the large database available and the well-defined dataspace. Several studies based on over 1000 subjects were reported in the recent past, especially examining CKD273, a classifier for assessment of chronic kidney disease based on 273 urine peptides. Interestingly, the most abundant urinary peptides are generally collagen fragments, which may have gone undetected for some time as they are typically modified via proline hydroxylation. The data available suggest that urinary peptides specifically depict inflammation and fibrosis, and may serve as a non-invasive tool to assess fibrosis, which appears to be a key driver in kidney and cardiovascular disease. The recent successful completion of the first urinary peptide guided intervention trial, PRIORITY, is expected to further spur clinical application of urinary peptidomics, aiming especially at early detection of chronic diseases, prediction of progression and prognosis of drug response. This article is protected by copyright. All rights reserved.

2.
Proteomics Clin Appl ; : e2000029, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32618437

RESUMO

PURPOSE: We investigated the peptidomes of spent hemodialysate, urine, and plasma, to shed light on peptide handling in the kidney. EXPERIMENTAL DESIGN: We collected 15 plasma, 15 urine and 13 spent hemodialysate samples from age and sex-matched subjects with chronic kidney disease. Peptide identification and quantification were performed with capillary electrophoresis-coupled mass spectrometry. RESULTS: We detected 6278 urinary peptides, 1743 plasma peptides and 1727 peptides from spent hemodialysate. Of these, we could assign sequences to 1580, 419 and 352 peptides respectively. We found a strong correlation in peptide abundance between urine and spent hemodialysate (P = 3e-21, Rho = 0.52), a moderately strong correlation between spent hemodialysate and plasma (P = 4.5e-5, Rho = 0.30), and no significant correlation between urine and plasma (P = 0.11, Rho = 0.094). Collagen and fibrinogen alpha peptides are highly abundant in all three body fluids. In spent hemodialysate, thymosin ß4 is one of the most abundant peptides, which is shown to be negatively associated with the estimated glomerular filtration rate (Rho = -0.39, p-value = 3.9e-81). CONCLUSION AND CLINICAL RELEVANCE: The correlation of peptide abundance in these three body fluids is lower than expected, supporting the hypothesis that tubular reabsorption has a major impact on urinary peptide content. Further investigation of thymosin ß4 in hemodialysis is thus warranted. This article is protected by copyright. All rights reserved.

3.
Int J Infect Dis ; 98: 227-229, 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32592907

RESUMO

Sodium-glucose co-transporter 2 (SGLT2) inhibitors exhibit impressive cardio-renal benefits in patients with a high cardiovascular risk. Genital yeast infections are important side effects of this class of drugs. We report a case of Candida glabrata sepsis secondary to a Candida infection of the urostomy of a patient on SGLT2 inhibitor therapy. In urostomy patients, one should critically evaluate the risk of mycotic infections against the cardiovascular and glycaemic benefits of SGLT2 inhibition. Urostomy patients without a high cardiovascular risk should not be treated with SGLT2 inhibitors.

4.
Eur J Endocrinol ; 183(3): 233-244, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32508317

RESUMO

Background: Patients with chronic kidney disease (CKD) have a high risk of premature cardiovascular diseases (CVD) and show increased mortality. Pro-neurotensin (Pro-NT) was associated with metabolic diseases and predicted incident CVD and mortality. However, Pro-NT regulation in CKD and its potential role linking CKD and mortality have not been investigated, so far. Methods: In a central lab, circulating Pro-NT was quantified in three independent cohorts comprising 4715 participants (cohort 1: patients with CKD; cohort 2: general population study; and cohort 3: non-diabetic population study). Urinary Pro-NT was assessed in part of the patients from cohort 1. In a 4th independent cohort, serum Pro-NT was further related to mortality in patients with advanced CKD. Tissue-specific Nts expression was further investigated in two mouse models of diabetic CKD and compared to non-diabetic control mice. Results: Pro-NT significantly increased with deteriorating renal function (P < 0.001). In meta-analysis of cohorts 1-3, Pro-NT was significantly and independently associated with estimated glomerular filtration rate (P ≤ 0.002). Patients in the middle/high Pro-NT tertiles at baseline had a higher all-cause mortality compared to the low Pro-NT tertile (Hazard ratio: 2.11, P = 0.046). Mice with severe diabetic CKD did not show increased Nts mRNA expression in different tissues compared to control animals. Conclusions: Circulating Pro-NT is associated with impaired renal function in independent cohorts comprising 4715 subjects and is related to all-cause mortality in patients with end-stage kidney disease. Our human and rodent data are in accordance with the hypotheses that Pro-NT is eliminated by the kidneys and could potentially contribute to increased mortality observed in patients with CKD.

5.
Int J Artif Organs ; : 391398820922240, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32400289

RESUMO

Incompatibility of dialysis procedure due to hypersensitivity against dialyzer material, currently mainly based on polysulfone and derivatives, cannot be assessed by routine laboratory tests. Although the frequency of such symptoms is suspected to be lower than 2%, it resembles an important clinical problem because dialysis procedures are frequently accompanied by symptoms of non-tolerability with reasons not being entirely clear. To enlighten the role of polysulfone hypersensitivity, we adapted known standardized material immune-toxicological tests (lymphocyte transformation test, basophil degranulation test) to the specific conditions of dialysis and polysulfone material sensitivity. We developed a method of polysulfone micronisation and measured humoral immune response of isolated patient's lymphocytes when incubated with polysulfone dispersion. Thirty-nine samples from 103 patients with suspected polysulfone hypersensitivity within the dialysis population of a nation-wide dialysis provider (n = 15.761 patients) showed positive results for type 1 (n = 19), type 4 (n = 18) or both type (n = 2) reactions. This is the first methodological report showing plausible in-vitro results of patients' samples concerning polysulfone intolerance. Further clinical and laboratory research is needed to define true polysulfone hypersensitivity and to enlighten the field of hypothetic subclinical material incompatibility in patients with impaired dialysis tolerability.

6.
Lancet Diabetes Endocrinol ; 8(4): 301-312, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32135136

RESUMO

BACKGROUND: Microalbuminuria is an early sign of kidney disease in people with diabetes and indicates increased risk of cardiovascular disease. We tested whether a urinary proteomic risk classifier (CKD273) score was associated with development of microalbuminuria and whether progression to microalbuminuria could be prevented with the mineralocorticoid receptor antagonist spironolactone. METHODS: In this multicentre, prospective, observational study with embedded randomised controlled trial (PRIORITY), we recruited people with type 2 diabetes, normal urinary albumin excretion, and preserved renal function from 15 specialist centres in ten European countries. All participants (observational cohort) were tested with the CKD273 classifier and classified as high risk (CKD273 classifier score >0·154) or low risk (≤0·154). Participants who were classified as high risk were entered into a randomised controlled trial and randomly assigned (1:1), by use of an interactive web-response system, to receive spironolactone 25 mg once daily or matched placebo (trial cohort). The primary endpoint was development of confirmed microalbuminuria in all individuals with available data (observational cohort). Secondary endpoints included reduction in incidence of microalbuminuria with spironolactone (trial cohort, intention-to-treat population) and association between CKD273 risk score and measures of impaired renal function based on estimated glomerular filtration rate (eGFR; observational cohort). Adverse events (particularly gynaecomastia and hyperkalaemia) and serious adverse events were recorded for the intention-to-treat population (trial cohort). This study is registered with the EU Clinical Trials Register (EudraCT 20120-004523-4) and ClinicalTrials.gov (NCT02040441) and is completed. FINDINGS: Between March 25, 2014, and Sept 30, 2018, we enrolled and followed-up 1775 participants (observational cohort), 1559 (88%) of 1775 participants had a low-risk urinary proteomic pattern and 216 (12%) had a high-risk pattern, of whom 209 were included in the trial cohort and assigned to spironolactone (n=102) or placebo (n=107). The overall median follow-up time was 2·51 years (IQR 2·0-3·0). Progression to microalbuminuria was seen in 61 (28%) of 216 high-risk participants and 139 (9%) of 1559 low-risk participants (hazard ratio [HR] 2·48, 95% CI 1·80-3·42; p<0·0001, after adjustment for baseline variables of age, sex, HbA1c, systolic blood pressure, retinopathy, urine albumin-to-creatinine ratio [UACR], and eGFR). Development of impaired renal function (eGFR <60 mL/min per 1·73 m2) was seen in 48 (26%) of 184 high-risk participants and 119 (8%) of 1423 low-risk participants (HR 3·50; 95% CI 2·50-4·90, after adjustment for baseline variables). A 30% decrease in eGFR from baseline (post-hoc endpoint) was seen in 42 (19%) of 216 high-risk participants and 62 (4%) of 1559 low-risk participants (HR 5·15, 95% CI 3·41-7·76; p<0·0001, after adjustment for basline eGFR and UACR). In the intention-to-treat trial cohort, development of microalbuminuria was seen in 35 (33%) of 107 in the placebo group and 26 (25%) of 102 in the spironolactone group (HR 0·81, 95% CI 0·49-1·34; p=0·41). In the safety analysis (intention-to-treat trial cohort), events of plasma potassium concentrations of more than 5·5 mmol/L were seen in 13 (13%) of 102 participants in the spironolactone group and four (4%) of 107 participants in the placebo group, and gynaecomastia was seen in three (3%) participants in the spironolactone group and none in the placebo group. One patient died in the placebo group due to a cardiac event (considered possibly related to study drug) and one patient died in the spironolactone group due to cancer, deemed unrelated to study drug. INTERPRETATION: In people with type 2 diabetes and normoalbuminuria, a high-risk score from the urinary proteomic classifier CKD273 was associated with an increased risk of progression to microalbuminuria over a median of 2·5 years, independent of clinical characteristics. However, spironolactone did not prevent progression to microalbuminuria in high-risk patients. FUNDING: European Union Seventh Framework Programme.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/urina , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Espironolactona/uso terapêutico , Adulto , Idoso , Albuminúria , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Diagnóstico Precoce , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteômica , Resultado do Tratamento
7.
Blood Purif ; 49(3): 356-363, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31812967

RESUMO

BACKGROUND/AIMS: Trajectory of heart rate variability (HRV) represents a noninvasive real-time measure of autonomous nervous system (ANS) and carries the capability of providing new insights into the hemodynamic compensation reserve during hemodialysis (HD). However, studies on HRV reproducibility during HD are scarce and did not refer to different reading periods. In this observational study, we aimed to establish the best suited and most reliable and reproducible HRV index in routine HD treatments including different reading rates. METHODS: HRV was characterized by standardized mathematical variation expressions of R/R' intervals: SD of all R/R' intervals (ms), square root of the root mean square of the sum of all differences between adjacent R/R' intervals (ms), percentage of consecutive R/R' intervals that differ by >50 ms (%), low-frequency spectral analysis HRV (LF, expressing sympathetic activity), and high-frequency HRV (HF, expressing parasympathetic activity). To compare robustness of these HRV indices during HD procedures, we compared HRV indices means between different HD sessions and controlled for association with clinical parameters. RESULTS: In 72 HD treatments of 34 patients, we detected the highest reproducibility (89%) of HRV measures when analyzing the low-frequency to high-frequency (LF/HF) ratio in long-term (3 h) readings. Long-term LF/HF was able to discriminate -between patients with and without heart failure NYHA classes ≥3 (p = 0.009) and type 2 diabetes (p = 0.023). We were unable to study relationships between ANS and intradialytic complications because they did not appear in our cohort. Short-term readings of HRV indices did not show any significance of pattern change during HD. CONCLUSION: In summary, our data provide evidence for high robustness of long-term LF/HF in analyzing HRV in HD patients using future automated monitoring systems. For short-term analysis, mathematical real-time analysis must evolve.

8.
Hypertension ; 75(1): 257-264, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31786986

RESUMO

Arterial baroreflex activation through electrical carotid sinus stimulation has been developed for the treatment of resistant hypertension. Previous studies suggested that the peripheral chemoreflex is tonically active in hypertensive patients and may inhibit baroreflex responses. We hypothesized that peripheral chemoreflex activation attenuates baroreflex efficacy evoked by electrical carotid sinus stimulation. We screened 35 patients with an implanted electrical carotid sinus stimulator. Of those, 11 patients with consistent acute depressor response were selected (7 men/4 women, age: 67±8 years, body mass index: 31.6±5.2 kg/m2, 6±2 antihypertensive drug classes). We assessed responses to electrical baroreflex stimulation during normoxia, isocapnic hypoxia (SpO2: 79.0±1.5%), and hyperoxia (40% end-tidal O2 fraction) by measuring heart rate, blood pressure, ventilation, oxygen saturation, end-tidal CO2 and O2 fractions, and muscle sympathetic nerve activity. During normoxia, baroreflex activation reduced systolic blood pressure from 164±27 to 151±25 mm Hg (mean±SD, P<0.001), heart rate from 64±13 to 61±13 bpm (P=0.002), and muscle sympathetic nerve activity from 42±12 to 36±12 bursts/min (P=0.004). Hypoxia increased systolic blood pressure 8±12 mm Hg (P=0.057), heart rate 10±6 bpm (P<0.001), muscle sympathetic nerve activity 7±7 bursts/min (P=0.031), and ventilation 10±7 L/min (P=0.002). However, responses to electrical carotid sinus stimulation did not differ between hypoxic and hyperoxic conditions: systolic blood pressure: -15±7 versus -14±8 mm Hg (P=0.938), heart rate: -2±3 versus -2±2 bpm (P=0.701), and muscle sympathetic nerve activity: -6±4 versus -4±3 bursts/min (P=0.531). We conclude that moderate peripheral chemoreflex activation does not attenuate acute responses to electrical baroreflex activation therapy in patients with resistant hypertension. These patients provided insight into human baroreflex-chemoreflex interactions that could not be gained otherwise.


Assuntos
Barorreflexo/fisiologia , Seio Carotídeo/fisiopatologia , Terapia por Estimulação Elétrica , Hipertensão/fisiopatologia , Idoso , Pressão Sanguínea/fisiologia , Estimulação Elétrica , Feminino , Frequência Cardíaca/fisiologia , Humanos , Hiperóxia/fisiopatologia , Hipertensão/terapia , Hipóxia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia
9.
Clin Kidney J ; 12(6): 814-820, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31808445

RESUMO

Background: Acute interstitial nephritis (AIN) is a renal injury causing renal function deterioration and requiring renal replacement therapy (RRT) in a substantial number of cases. Therapy is based on withdrawal of suspicious causative drugs or the underlying diseases and/or steroid application if renal function is not restored after cessation of the underlying condition. Hard clinical evidence for augmenting steroid therapy is not available. Methods: We reviewed the course and diagnosis for >20 years among all 1126 biopsied samples of our tertiary renal centre. Results: 49 (4.4%) were diagnosed with primary AIN, corresponding to an annual incidence of 1/100 000 population; 17 out of 49 biopsy-proven AIN patients required short-term or long-term (n = 5) RRT. According to a combined outcome criterion of coming off dialysis and/or reaching serum creatinine <200 µmol/L, 19 patients reached recovery whereas 20 did not. Among 39 patients with a comprehensive clinical and histopathological data set, presence of cortical scars, AIN histological activity (acute leucocyte infiltrates) and proteinuria were baseline parameters discriminating significantly between groups with or without recovery. No associations with the presence of specific drugs were found. Therapeutic use of steroids was associated with a lower probability of recovery (P = 0.008), presumably due to inclusion bias. Conclusions: Following our basic finding of the importance of histopathological parameters of acuity associated with recovery, we argue for the inauguration of grading measures to characterize this issue quantitatively and make it usable for future controlled investigations. Finally, we provide a suggestion for a therapeutic algorithm in the management of AIN.

12.
Anal Cell Pathol (Amst) ; 2019: 8389765, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019876

RESUMO

Background: Chronic or intercurrent alterations of the immune system in patients with end-stage renal disease (CKD) and intermittent hemodialysis (CKD5D, HD) have been attributed to an acute rejection of renal allograft. Methods: Leukocyte subsets in flow cytometry, complement activation, and concentrations of TGFß, sCD30 (ELISA), and interleukins (CBA) of fifteen patients eligible for renal transplantation were analyzed before, during, and after a regular HD. Results: Before HD, the median proportion of CD8+ effector cells, CD8+ CCR5+ effector cells, and HLA-DR+ regulatory T cells as well as the median concentration of soluble CD30 increased and naive CD8+ T cells decreased. During HD, there was a significant decrease in CD4- CD8- T cells (p < 0.001) and an increase in CD25+ T cells (p = 0.026), sCD30 (p < 0.001), HLA-DR+ regulatory T cells (p = 0.005), and regulatory T cells (p = 0.003). TGFß and sCD30 increased significantly over time. The activity of the classical complement pathway started to slightly increase after the first hour of HD and lasted until fifteen minutes after finishing dialysis. The decrease in the functional activity of the alternative pathway was only transient and was followed by a significant increase within 15 minutes after finishing the treatment. Conclusion: HD might interact with the allograft outcome by influencing T cell subsets and activation of the complement system in a biphasic course.


Assuntos
Transplante de Rim/efeitos adversos , Diálise Renal/efeitos adversos , Adulto , Idoso , Linfócitos T CD8-Positivos/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Subunidade alfa de Receptor de Interleucina-2/imunologia , Interleucinas/metabolismo , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Linfócitos T/metabolismo , Adulto Jovem
13.
J Clin Hypertens (Greenwich) ; 20(10): 1519-1526, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30203514

RESUMO

Baroreflex activation therapy (BAT) is approved for the treatment of resistant hypertension. In addition to blood pressure (BP) reduction, pilot studies suggested several organoprotective effects of BAT. Thirty-two patients with resistant hypertension were prospectively treated with BAT. Besides office BP and 24-hour ambulatory BP (ABP) measurements, detection of a urinary proteome-based classifier (CKD273), which has been shown to predict chronic kidney disease (CKD) progression, was carried out at baseline and after 6 months of BAT. Office BP significantly decreased from 170 ± 25/90 ± 18 to 149 ± 29/82 ± 18 mm Hg. Analysis of CKD273 score and eGFR with CKD-EPI equation at baseline revealed strong correlation (r = 0.568, P < 0.001). After 6 months of BAT, there was no significant change in CKD273 score (-0.061 [95% CI: -0.262 to 0.140], P = 0.601). However, by stratification of the data regarding ABP response, there was a statistically significant (P = 0.0113) reduction in the CKD273 score from a mean of 0.161 [95% CI: -0.093 to 0.414] to -0.346 [95% CI: -0.632 to -0.060] after BAT in patients with systolic ABP decrease of ≥5 mm Hg. These data emphasized potential nephroprotective effects of BAT in patients with sufficient BP response.


Assuntos
Barorreflexo/fisiologia , Hipertensão/terapia , Rim/fisiopatologia , Insuficiência Renal Crônica/prevenção & controle , Idoso , Anti-Hipertensivos/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial/métodos , Terapia por Estimulação Elétrica/instrumentação , Terapia por Estimulação Elétrica/métodos , Eletrodos Implantados , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pressorreceptores/fisiopatologia , Estudos Prospectivos , Proteoma/análise , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/urina , Resultado do Tratamento
14.
Exp Clin Endocrinol Diabetes ; 126(6): 349-356, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29475205

RESUMO

INTRODUCTION: Endocrine disorders of the pituitary axes are frequent in patients with hemodialysis (CKD5D). The aim of this multicenter study (Leipzig (L), Quedlinburg and Blankenburg in the Harz region (Hz)) in CKD5D patients was to evaluate influences of CKD5D related factors, morphological and biochemical parameters, and serum iodine and prolactin concentrations on the pituitary-thyroid axis. PATIENTS AND METHODS: 170 patients (L n=58; Hz n=112) were included in this prospective, non-interventional, cross-sectional study. Mann-Whitney-U-test and bivariate correlation analyses with Spearman-Rho test (r correlation coefficient) were used in statistical analysis. RESULTS: TSH was higher in patients with prolactin concentrations>370 mIU/l (p=0.013), in patients with high flux membranes (p=0.0013) and in patients with longer dialysis vintage (p=0.04). Median iodine serum concentrations were slightly elevated in the Leipzig cohort (p=0.001) and correlated with fT4 (p<0.001, r=0.43) and albumin (p=0.001, r=0.245) but not with morphological signs. Albumin was correlated with fT3 (p<0.001, r=0.339) and fT4 (p<0.001, r=0.421). Prolactin was correlated with residual excretion rate (p=0.001, r=- 0.303) and thyroid volume (p=0.027, r=0.217). CONCLUSIONS: In the assessment of the thyroid status in CKD5D patients, the synopsis of the clinical and nutritional status, comorbidities, ultrasound of the thyroid gland and laboratory results is necessary for further intervention with hormone replacement. Standardized reference values of the pituitary-thyroid axis should be critically evaluated and are still lacking in CKD5D.


Assuntos
Falência Renal Crônica , Hipófise/fisiopatologia , Prolactina/metabolismo , Diálise Renal , Glândula Tireoide/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Doenças Endêmicas , Feminino , Alemanha/epidemiologia , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/metabolismo , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/complicações , Doenças da Hipófise/epidemiologia , Doenças da Hipófise/metabolismo , Testes de Função Hipofisária , Hipófise/metabolismo , Diálise Renal/estatística & dados numéricos , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/metabolismo , Testes de Função Tireóidea , Glândula Tireoide/metabolismo
15.
Clin Nephrol ; 88(12): 317-327, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29115212

RESUMO

INTRODUCTION: The possible confounding influence of investigator-related preferences, available histological techniques, and healthcare systems on the frequencies and incidences of primary and secondary nephropathies was evaluated in this long-term observation. MATERIALS AND METHODS: The observation time from 1983 to 2010 was divided in regard to the political regimes: a) prior to and after German reunification: German Democratic Republic (GDR, period 1 from 1983 to 1990)/Federal Republic of Germany (FRG, period 2 from 1990 to 2010); and the two heads of the division of nephrology, b) conductor 1 (1983 - 2006) and conductor 2 (2006 - 2010). 467 kidney biopsies at the University Hospital of Leipzig were included in our analysis. RESULTS: In period 1, due to the unavailability of immunofluorescence methods, mesangioproliferative glomerulonephritis (MesP) was the most dominating nephropathy. In period 2, IgA nephropathy (IgAN) was the most common nephropathy (17%). IgAN was followed by crescentic glomerulonephritis (13%), hypertensive nephropathy (10%), minimal-change disease, and membranous glomerulonephritis (each 9%). From period 1 to period 2, MesP/IgAN (62% to 16%), membranoproliferative glomerulonephritis and postinfectious glomerulonephritis decreased significantly (p < 0.05). IgAN decreased significantly (p < 0.05) from conductor 1 to conductor 2 (21% to 6%), while diabetic nephropathy significantly increased. Focal-segmental glomerulosclerosis (FSGS) had the highest incidence rate with 1.0, followed by IgAN with 0.8 (per 100,000 per year). CONCLUSION: In a nearly ethnically identical cohort, we have demonstrated that confounding factors, e.g., healthcare systems and preferences of conductors, have a strong influence - more than 10-fold variance - on frequency and incidence on the spectrum of nephropathies.
.


Assuntos
Assistência à Saúde , Nefropatias/epidemiologia , Política , Adulto , Biópsia , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Rim/patologia , Masculino , Pessoa de Meia-Idade
16.
Nephrol Dial Transplant ; 32(10): 1637-1644, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28339962

RESUMO

Background: Follistatin-like 3 (FSTL3) is a novel cytokine that regulates insulin sensitivity and counteracts activin/myostatin signalling. In the present study, regulation of FSTL3 in renal dysfunction was investigated in both human chronic kidney disease (CKD) and acute kidney dysfunction (AKD). Furthermore, mFSTL3 expression was analysed in insulin-sensitive tissues in a mouse model of CKD. Methods: Circulating FSTL3 was quantified by enzyme-linked immunosorbent assay in 581 patients with CKD covering the whole spectrum of estimated glomerular filtration rate (eGFR) categories from G1 to G5. Furthermore, FSTL3 was measured in 61 patients before and within 30 h after elective unilateral nephrectomy, an established model of AKD. Moreover, mFSTL3 mRNA expression was investigated in an animal CKD model, that is, eNOS-/-db/db mice, and compared with littermate controls. Results: Median circulating FSTL3 levels significantly and continuously increased with deteriorating renal function (eGFR category G1: 6.1; G2: 8.2; G3: 12.7; G4: 18.5; G5: 32.1 µg/L; P < 0.001). In both human CKD and AKD, renal dysfunction remained the strongest independent predictor of FSTL3 serum concentrations in multivariate analyses. FSTL3 was independently associated with an adverse cardiometabolic profile. In CKD mice, hepatic mFSTL3 mRNA expression was increased more than 6-fold as compared with controls. Conclusions: Circulating FSTL3 is significantly and independently associated with renal function in both patients with CKD and AKD. Hepatic mFSTL3 mRNA upregulation might contribute to increased FSTL3 levels in CKD. Our results are in agreement with the hypothesis that FSTL3 is eliminated by the kidneys and might counteract adverse activin/myostatin signalling observed in renal dysfunction.


Assuntos
Proteínas Relacionadas à Folistatina/sangue , Insuficiência Renal Crônica/sangue , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Casos e Controles , Células Cultivadas , Estudos Transversais , Feminino , Proteínas Relacionadas à Folistatina/genética , Expressão Gênica , Taxa de Filtração Glomerular , Humanos , Resistência à Insulina , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia , Regulação para Cima
17.
J Hypertens ; 35(7): 1496-1501, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28267039

RESUMO

BACKGROUND: Baroreceptor-activating therapy (BAT) has been shown to control resistant hypertension in one sham-controlled and further observational studies. Incremental but significant reincrease of blood pressure (BP) have been described after open-label temporary withdrawal of such therapy. METHOD: Our study in 16 randomized patients investigated the course of automated office, ambulatory, and home BP in a randomized, controlled cross-over design. RESULTS: After 4 weeks of blinded and randomized withdrawal in hypertension-controlled long-term carriers of BAT (2.67 ±â€Š1.3 years, 145/104 mmHg), the primary end point of 35 mmHg difference, similar to initial BP drop after BAT initiation, was not reached in any patient. Ambulatory BP rose significantly during BAT off by 10/8 ±â€Š4/3 mmHg (3.13/2.10, P = 0.007/0.002) and automated office BP by 10/4 ±â€Š2/1 (4.17/0.58, P = 0.005/0.03) at 4 weeks after BAT on while mean home BP did not change significantly by 2/2 ±â€Š3/2 mmHg (-5.9/-3.5, P = 0.6/0.5). CONCLUSION: Our data in a limited study population show, that BP rise after temporary BAT withdrawal is significant but does not reach a magnitude comparable with the initial drop after de novo implantation. Such results points to preserved hypertension control after electrical BAT withdrawal and deserves further pathophysiological and clinical clarification.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Terapia por Estimulação Elétrica/métodos , Hipertensão/terapia , Pressorreceptores/fisiopatologia , Adulto , Idoso , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial , Monitorização Ambulatorial da Pressão Arterial/métodos , Terapia Combinada , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
18.
J Am Soc Hypertens ; 11(2): 81-91, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28065708

RESUMO

Baroreflex activation therapy (BAT) is a device-based therapy for patients with treatment-resistant hypertension. In a randomized, controlled trial, the first-generation system significantly reduced blood pressure (BP) versus sham. Although an open-label validation study of the second-generation system demonstrated similar BP reductions, controlled data are not presently available. Therefore, this investigation compares results of first- and second-generation BAT systems. Two cohorts of first-generation BAT system patients were generated with propensity matching to compare against the validation group of 30 second-generation subjects. The first cohort was drawn from the first-generation randomized trial sham group and the second cohort from the active therapy group. Safety and efficacy were compared for the second-generation group relative to the first generation. At 6 months, second-generation BAT outperformed first-generation sham systolic BP reduction by 20 ± 28 mm Hg (mean ± standard deviation, P = .008), while BP reduction in first- and second-generation active groups was similar. At 12 months, efficacy was comparable between all three groups after the sham group had received 6 months of therapy; 47% of second-generation patients achieved goal systolic BP of 140 mm Hg or less after 12 months, comparable to 50% of patients at goal in the first-generation group (P > .999). Implant procedure time, system/procedural safety, and pulse generator longevity improved with the second-generation system. Propensity-matched cohort analysis of the first- and second-generation BAT systems suggests similar therapeutic benefit and superior BP reduction of the second-generation system relative to sham control. Implantation procedure duration and perioperative safety were improved with the second-generation device. These findings should be validated in a prospective randomized trial.


Assuntos
Vasoespasmo Coronário/terapia , Terapia por Estimulação Elétrica/instrumentação , Terapia por Estimulação Elétrica/métodos , Eletrodos Implantados , Hipertensão/terapia , Idoso , Anti-Hipertensivos/uso terapêutico , Barorreflexo/fisiologia , Determinação da Pressão Arterial , Terapia por Estimulação Elétrica/efeitos adversos , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Pontuação de Propensão , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Resultado do Tratamento
19.
Nephrol Dial Transplant ; 32(12): 2079-2089, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27984204

RESUMO

Background: In spite of its invasive nature and risks, kidney biopsy is currently required for precise diagnosis of many chronic kidney diseases (CKDs). Here, we explored the hypothesis that analysis of the urinary proteome can discriminate different types of CKD irrespective of the underlying mechanism of disease. Methods: We used data from the proteome analyses of 1180 urine samples from patients with different types of CKD, generated by capillary electrophoresis coupled to mass spectrometry. A set of 706 samples served as the discovery cohort, and 474 samples were used for independent validation. For each CKD type, peptide biomarkers were defined using statistical analysis adjusted for multiple testing. Potential biomarkers of statistical significance were combined in support vector machine (SVM)-based classifiers. Results: For seven different types of CKD, several potential urinary biomarker peptides (ranging from 116 to 619 peptides) were defined and combined into SVM-based classifiers specific for each CKD. These classifiers were validated in an independent cohort and showed good to excellent accuracy for discrimination of one CKD type from the others (area under the receiver operating characteristic curve ranged from 0.77 to 0.95). Sequence analysis of the biomarkers provided further information that may clarify the underlying pathophysiology. Conclusions: Our data indicate that urinary proteome analysis has the potential to identify various types of CKD defined by pathological assessment of renal biopsies and current clinical practice in general. Moreover, these approaches may provide information to model molecular changes per CKD.


Assuntos
Biomarcadores/urina , Proteoma/análise , Proteômica/métodos , Insuficiência Renal Crônica/diagnóstico , Urinálise/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Insuficiência Renal Crônica/urina
20.
PLoS One ; 11(12): e0168905, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28033403

RESUMO

Dynamic tissue perfusion measurement (DTPM) is a pre-described and available method in pediatric ultrasound to quantify tissue perfusion in renal Doppler ultrasound by particular video analysis software. This study evaluates DTPM during single and between repeated visits after 6 months, calibrates repeated DTPM within different region of interest (ROI) and compares DTPM with kidney function markers in adult patients with early diabetic nephropathy (n = 17). During repeated measurements, no association of readings at the same patients in the same (n = 3 readings) as well as repeated visit (n = 2 visits) could be retrieved. No association between DTPM, MDRD-GFR, albuminuria, age and duration of diabetes was observed. These negative results are presumably related to inconsistency of DTPM due to non-fixed ROI position as could be shown in calibrating series. Further development of the method should be performed to enable reproducible DTPM readings in adults.


Assuntos
Nefropatias Diabéticas/diagnóstico por imagem , Nefropatias Diabéticas/fisiopatologia , Fluxo Sanguíneo Regional , Ultrassonografia Doppler em Cores , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Rim/irrigação sanguínea , Rim/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
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