The nondipping blood pressure (BP) pattern, characterized by a less than 10% decline in sleep-time BP compared to awake-time values, is prevalent in individuals with type 1 diabetes mellitus (T1DM) and is associated with increased cardiovascular (CV) risk.

This review discusses the prevalence, pathophysiological mechanisms, complications, and management strategies of the nondipping pattern in T1DM. The nondipping pattern is linked to poor cardiac autonomic function, higher rates of albuminuria, early markers of diabetic kidney disease, and increased arterial stiffness. It is also associated with a two-fold increase in all-cause mortality.

Despite its clinical significance, there is no consensus on specific treatment recommendations for nondippers with T1DM. While some studies suggest that bedtime administration of antihypertensive medications, such as ACE inhibitors and angiotensin II receptor blockers, can improve the dipping pattern and reduce CV events, these findings are primarily based on studies in the general hypertensive population. Emerging evidence also indicates a potential role for vitamin D supplementation and lifestyle interventions in improving BP variability.

Further research is needed to develop evidence-based management strategies tailored to nondippers with T1DM, aiming to reduce CV risk and improve long-term outcomes.

This study aimed to evaluate the role of the 24-Hour Ambulatory Blood Pressure Monitoring (ABPM) as a possible predictor of vascular outcomes in office normotensive people with type 1 diabetes mellitus (T1DM).

This is a systematic review including cohort studies from the Embase, PubMed/Medline, and Web of Science databases on people with T1DM undergoing ABPM and subsequent evaluation of vascular complications. Measurements of difference (MD) were obtained using random effect model meta-analysis.

We found 364 articles and 49 duplicates. Seven studies were included, comprising 635 participants aged 25.8 ± 6.2 years. Most (57.5 %) were men, mean duration of diabetes was 11.8 ± 5.3 years, mean glycated hemoglobin level among participants was 8.5 % ± 1.6 %, and mean follow-up time was 4.2 years. Lower night systolic blood pressure MD - 4.37 mmHg (p = 0.0009) and night diastolic blood pressure MD - 3.97 mmHg (p < 0.0001) were associated with lower incidence of albuminuria. People withT1DM who presented no beginning or progression of retinopathy were those with lower night diastolic blood pressure MD - 3.62 mmHg (p = 0.042), diurnal diastolic blood pressure MD - 2.69 mmHg (p = 0.0138), and 24-hour diastolic blood pressure MD - 3.65 mmHg (p = 0.037).

Small mean differences in blood pressure parameters, as measured by ABPM, between people with T1DM are associated with a lower incidence or risk of progression of nephropathy and retinopathy.

Cardiac circadian rhythms are an important regulator of body functions, including cardiac activities and blood pressure. Disturbance of circadian rhythm is known to trigger and aggravate various cardiovascular diseases. Thus, modulating the circadian rhythm can be used as a therapeutic approach to cardiovascular diseases. Through this work, we intend to discuss the current understanding of cardiac circadian rhythms, in terms of quantifiable parameters like BP and HR. We also elaborate on the molecular regulators and the molecular cascades along with their specific genetic aspects involved in modulating circadian rhythms, with specific reference to cardiovascular health and cardiovascular diseases. Along with this, we also presented the latest pharmacogenomic and metabolomics markers involved in chronobiological control of the cardiovascular system along with their possible utility in cardiovascular disease diagnosis and therapeutics. Finally, we reviewed the current expert opinions on chronotherapeutic approaches for utilizing the conventional as well as the new pharmacological molecules for antihypertensive chronotherapy.

In the last decades, a significant increase in the incidence of diabetic kidney disease (DKD) was observed concomitant with rising diabetes mellitus (DM) incidence. Kidney disease associated with DM in children and adolescents is represented by persistent albuminuria, arterial hypertension, progressive decline in estimated glomerular filtration rate to end-stage renal disease and increased cardiovascular and all-cause morbidity and mortality of these conditions. In medical practice, the common and still the "gold standard" marker for prediction and detection of diabetic kidney involvement in pediatric diabetes is represented by microalbuminuria screening even if it has low specificity to detect early stages of DKD. There are some known limitations in albuminuria value as a predictor biomarker for DKD, as not all diabetic children with microalbuminuria or macroalbuminuria will develop end-stage renal disease. As tubular damage occurs before the glomerular injury, tubular biomarkers are superior to the glomerular ones. Therefore, they may serve for early detection of DKD in both type 1 DM and type 2 DM. Conventional and new biomarkers to identify diabetic children and adolescents at risk of renal complications at an early stage as well as renoprotective strategies are necessary to delay the progression of kidney disease to end-stage kidney disease. New biomarkers and therapeutic strategies are discussed as timely diagnosis and therapy are critical in the pediatric diabetic population.

Given the emerging knowledge that circadian rhythmicity exists in every cell and all organ systems, there is increasing interest in the possible benefits of chronotherapy for many diseases. There is a well-documented 24-h pattern of blood pressure with a morning surge that may contribute to the observed morning increase in adverse cardiovascular events. Historically, antihypertensive therapy involves morning doses, usually aimed at reducing daytime blood pressure surges, but an absence of nocturnal dipping blood pressure is also associated with increased cardiovascular risk.

To more effectively reduce nocturnal blood pressure and still counteract the morning surge in blood pressure, a number of studies have examined moving one or more antihypertensives from morning to bedtime dosing. More recently, such studies of chronotherapy have studied comorbid populations including obstructive sleep apnea, chronic kidney disease, or diabetes. Here, we summarize major findings from recent research in this area (2013-2017). In general, nighttime administration of antihypertensives improved overall 24-h blood pressure profiles regardless of disease comorbidity. However, inconsistencies between studies suggest a need for more prospective randomized controlled trials with sufficient statistical power. In addition, experimental studies to ascertain mechanisms by which chronotherapy is beneficial could aid drug design and guidelines for timed administration.

Evening dosing regimen drug therapy on blood pressure (BP) control is used widely, but its clinical benefits and preservation or re-establishment of the normal 24-h BP dipping pattern in chronic kidney disease (CKD) patients is not known.

To investigate the effect of an evening dosing regimen of antihypertensive drugs on BP patterns of CKD patients with hypertension.

A systematic review was conducted by searching PUBMED, EMBASE, ASN-ONLINE, the Cochrane Library and the reference lists of relevant articles of published papers. All trials designed to evaluate the effects of evening versus morning dosing regimen drug therapy for CKD patients with hypertension were included. Meta-analysis was performed using random or fixed effects models.

Five randomised controlled trials and one comparative study, including 3732 patients, met the inclusion criteria. Compared with morning dosing regimen drug therapy, evening administration of antihypertensive medication was associated with a significant reduction of 40% in non-dipper BP patterns (risk ratio (RR), 95% CI, (0.43, 0.84)). We noted a significant decrease in nocturnal systolic blood pressure (SBP) (MD -3.17 mmHg, 95% CI (-5.41, -0.94)), a significant reduction in nocturnal diastolic blood pressure (DBP) (MD -1.37 mmHg, 95% CI (-2.05, -0.69)) and a significant increase in awake SBP (MD 1.15 mmHg, 95% CI (0.10, 2.19)) in patients assigned to the evening dosing regimen drug therapy group. Patients showed no significant differences for all-cause mortality and cardiovascular mortality.

This review shows that evening dosing regimen drug therapy could reverse non-dipper BP patterns in hypertensive CKD patients.

Adolescents with Type 1 diabetes mellitus (T1DM) are at risk for hyperfiltration and elevated urinary albumin-to-creatinine ratio (ACR), which are early indicators of diabetic nephropathy. Adolescents with T1DM also develop early changes in blood pressure, cardiovascular structure, and function. Our aims were to define the relationships between hyperfiltration, ACR, and 24-h ambulatory blood pressure over time in adolescents with T1DM. Normotensive, normoalbuminuric adolescents ( n = 98) with T1DM underwent baseline and 2-yr 24-h ambulatory blood pressure monitoring, glomerular filtration rate (eGFR) estimated by cystatin C (Larsson equation), and ACR measurements. Linear regression models adjusted for diabetes duration, sex, and HbA1c were used to determine associations. Hyperfiltration (eGFR ≥ 133 ml/min) was present in 31% at baseline and 21% at 2-yr follow-up. Hyperfiltration was associated with greater odds of rapid GFR decline (>3 ml·min-1·yr-1) [OR: 5.33, 95%; CI: 1.87-15.17; P = 0.002] over 2 yr. Natural log of ACR at baseline was associated with greater odds of hyperfiltration (OR: 1.71, 95% CI: 1.00-2.92; P = 0.049) and 2-yr follow-up (OR: 2.14, 95%; CI: 1.09-4.19; P = 0.03). One SD increase in eGFR, but not ln ACR, at 2-yr follow-up conferred greater odds of nighttime nondipping pattern (OR: 1.96, 95% CI: 1.06-3.63; P = 0.03). Hyperfiltration was prevalent at baseline and at 2-yr follow-up, predicted rapid decline in GFR, and was related to ACR. Elevated GFR at 2-yr follow-up was associated with nighttime nondipping pattern. More work is needed to better understand early relationships between renal hemodynamic and systemic hemodynamic changes in adolescents with T1DM to reduce future cardiorenal complications.

To investigate the effects of chronotherapy on blood pressure in patients with chronic kidney disease (CKD).

We searched PUBMED, EMBASE, ASN-ONLINE, the Cochrane Library and the reference articles of published papers without language restriction, for randomized and non-randomized trials that assessed the effect of chronotherapy versus morning dosing regimen drug therapy for CKD patients with hypertension. Meta-analysis was done with random-effect models.

After application of inclusion/exclusion criteria, three randomized controlled trials including 3380 patients were analyzed. Compared with morning dosing regimen drug therapy, chronotherapy was associated with a significant decrease of 3.55% in sleep-time relative decline of systolic blood pressure (SBP) (mean difference [MD], 95% CI, [0.22, 6.88]). In the chronotherapy group, we noted a significant decrease in nocturnal SBP (MD -3.79 mmHg, 95% CI, [-7.18, -0.41]) and nocturnal diastolic blood pressure (MD -1.55 mmHg, 95% CI. [- 2.28, -0.82]), but there was a small increase in awake SBP by 1.19 mmHg (MD, 95% CI, [0.06, 2.31]). No significant difference was noted in all-cause mortality and cardiovascular mortality.

This meta-analysis suggests that chronotherapy could reduce nocturnal BP in hypertensive CKD patients.

To evaluate relationships between early alterations in blood pressure and the progression of microvascular complications of diabetes in clinically-normotensive patients with type 1 diabetes (T1DM).

In a prospective observational study of 85 normotensive T1DM patients without microalbuminuria, blood pressure (BP) was monitored over 24h using the ambulatory blood pressure monitoring (ABPM) system at baseline and 7years later. Development or progression of microalbuminuria, retinopathy and hypertension was evaluated.

Initially, 20 patients (24%) were diagnosed with masked hypertension and 31 (37%) with non-dipper pattern as the only pathological findings. At 7years: 1) twenty-seven patients (32%) had progression of retinopathy related to the nocturnal diastolic blood pressure (BPD) (OR:1.122; p=0.034) and final non-dipper pattern (OR:5.857; p=0.005); 2) seven patients (10%) developed microalbuminuria for which nocturnal systolic blood pressure (BPS) was a risk factor (OR:1.129; p=0.007); 3) five of the normotensive patients (9%) progressed to hypertension; historic HbA1c (OR:2.767; p=0.046) and nocturnal BPD (OR:1.243; p=0.046) being the related risk factors. BPD level ≥65mmHg was associated with an increase in progression of retinopathy and hypertension.

In T1DM patients there is an elevated prevalence of BP alterations, detected using ABPM. Alterations in nocturnal BP predispose to development/progression of microvascular complications and overt hypertension.

Patients with type 1 diabetes (DM-1) have an increased mortality and morbidity risk compared to non-diabetic subjects. Even not recognized clinically at the early period of disease; patients with DM-1 show subtle neurological and cardiovascular abnormalities which is partly responsible for the increased mortality. One of these abnormalities is the disruption of circadian rhythms. Various factors such as autonomic dysfunction, sleep disturbance, smoking, cardiac and kidney function, atherosclerosis, arterial stiffness are suggested to cause these disturbances. Additionally these abnormalities have also implications regarding target organ damage such as microalbuminuria, retinopathy, and structural changes in glomeruli. Surprisingly, there are scarce data regarding the effect of tight blood glucose control and insulin on circadian rhythms in patients with DM-1. By the light of aforementioned data this review will try to summarize causes and consequences of disruption of circadian rhythms and the impact on glycemic control on these issues in patients with DM-1.

More than two decades ago, hyperfiltration (HF) in diabetes was postulated to be a maladaptive response observed early in the course of diabetic kidney disease (DKD), which may eventually predispose to irreversible damage to nephrons and development of progressive renal disease. Despite this, the potential mechanisms leading to renal HF in diabetes are not fully understood, although several hypotheses have been proposed, including alterations in glomerular haemodynamic function and tubulo-glomerular feedback. Furthermore, the role of HF as a causative factor in renal disease progression is still unclear and warrants further prospective longer-term studies. Although HF has been entrenched as the first stage in the classic albuminuric pathway to end-stage renal disease in DKD, and HF has been shown to predict the progression of albuminuria in many, but not all studies, the concept that HF predisposes to the development of chronic kidney disease (CKD) stage 3, that is, glomerular filtration rate (GFR) decline to<60mL/min/1.73m(2), remains to be proved. Further long-term studies of GFR gradients therefore are required to establish whether HF ultimately leads to decreased kidney function, after adjustment for glycaemic control and other confounders. Whether reversal of HF with therapeutic agents is protective against reducing the risk of development of albuminuria and renal impairment is also worth investigating in prospective randomized trials.

To investigate the prevalence of nocturnal blood pressure dipping among obese prepubertal and early pubertal children and to analyse the relationship between dipping and measures of insulin-glucose metabolism or sleep-disordered breathing.

We studied 76 obese children (41% girls) under clinical care, with an average age of 10.4 ± 1.7 and a body mass index Z-score (BMI Z-score) of 6.2 ± 1.6. We performed a 24-h ambulatory blood pressure measurement. Non-dipping was defined as a nocturnal blood pressure reduction of <10%. We calculated measures of insulin-glucose metabolism from the performed frequently sampled intravenous glucose-tolerance test and from fasting blood samples. Overnight sleep polygraph recordings were performed to assess sleep-disordered breathing.

Forty-two percent of the children were systolic non-dippers, and 17% were diastolic non-dippers. There were no associations between systolic or diastolic dipping and measures of insulin-glucose metabolism after adjustments for BMI Z-score, gender and pubertal status. There were no associations between dipping and measures of sleep-disordered breathing.

Nocturnal non-dipping was two times higher among severely obese, prepubertal and early pubertal children, compared to previous reports among children in general. There were no associations between nocturnal dipping and insulin-glucose metabolism or measures of sleep-disordered breathing in this group.

Patients with type 1 diabetes mellitus (DM) and renal hyperfiltration also exhibit systemic microvascular abnormalities, including endothelial dysfunction. The effect of renal hyperfiltration on systemic blood pressure (BP) is less clear. We therefore measured BP, renal hemodynamic function and circulating renin angiotensin aldosterone system (RAAS) mediators in type 1 DM patients with hyperfiltration (n = 36, DM-H, GFR≥135 ml/min/1.73 m(2)) or normofiltration (n = 40, DM-N), and 56 healthy controls (HC). Since renal hyperfiltration represents a state of intrarenal RAAS activation, we hypothesized that hyperfiltration would be associated with higher BP and elevated levels of circulating RAAS mediators.

BP, glomerular filtration rate (GFR - inulin), effective renal plasma flow (paraaminohippurate) and circulating RAAS components were measured in DM-H, DM-N and HC during clamped euglycemia (4-6 mmol/L). Studies were repeated in DM-H and DM-N during clamped hyperglycemia (9-11 mmol/L).

Baseline GFR was elevated in DM-H vs. DM-N and HC (167±6 vs. 115±2 and 115±2 ml/min/1.73 m(2), p<0.0001). Baseline systolic BP (SBP, 117±2 vs. 111±2 vs. 109±1, p = 0.004) and heart rate (76±1 vs. 67±1 vs. 61±1, p<0.0001) were higher in DM-H vs. DM-N and HC. Despite higher SBP in DM-H, plasma aldosterone was lower in DM-H vs. DM-N and HC (42±5 vs. 86±14 vs. 276±41 ng/dl, p = 0.01). GFR (p<0.0001) and SBP (p<0.0001) increased during hyperglycemia in DM-N but not in DM-H.

DM-H was associated with higher heart rate and SBP values and an exaggerated suppression of systemic aldosterone. Future work should focus on the mechanisms that explain this paradox in diabetes of renal hyperfiltration coupled with systemic RAAS suppression.

The diagnosis of hypertension (HTN)/normotension (NT) on ambulatory blood pressure monitoring (ABPM) is usually based on systolic (SBP) or diastolic blood pressure (DBP). The goal of this study was to analyze whether inclusion of mean arterial pressure (MAP) improves the detection of HTN on ABPM.

We retrospectively studied ABPM records in 229 children (116 boys, median age = 15.3 years) who were referred for evaluation of HTN. A diagnosis of HTN was made if: (A) MAP or SBP or DBP was ≥ 1.65 SDS (95th percentile); (B) SBP or DBP was ≥ 1.65 SDS (95th percentile), during 24-h or daytime or night-time in both definitions.

Using definition A, 46/229 patients had HTN compared to definition B by which only 37/229 patients had HTN (p = 0.001). The level of agreement between the two definitions was very good (kappa = 0.86 ± 0.04), however nine patients (19.5 %) were missed by not using MAP in the definition of HTN. These nine patients had only mild HTN with a median Z score of 1.69.

The inclusion of MAP in the definition of ambulatory HTN significantly increased the number of hypertensive patients. MAP may be very helpful in detecting mild HTN in patients with normal/borderline SBP and DBP.

Nondipping blood pressure (BP) pattern is a potential independent risk factor for chronic kidney disease (CKD). Bedtime administration of valsartan is considered to normalize circadian rhythm and protect the kidneys and heart in CKD patients. However, more clinical trials are needed to confirm this benefit. Sixty patients with nondipping BP pattern and thirty patients with dipping BP pattern were enrolled in this study, and the patients with nondipping BP pattern were randomly divided into two groups and treated with bedtime or awakening doses of valsartan (80-320 mg). Nondipping BP patients treated with bedtime doses of valsartan showed a greater reduction in 24-hour proteinuria and bedtime proteinuria, a greater delayed decline in estimated glomerular filtration rate, and more protection against myocardial hypertrophy (P<.05) compared with patients with the nondipping BP pattern treated with the awakening dose (P<.05). This was similar to patients with dipping BP. No severe clinical complications were recorded in these patients. Valsartan with bedtime dosing in CKD patients with the nondipping BP pattern have better renal and cardiovascular protection. Antihypertensive "chronotherapy" may be useful in clinical practice for CKD patients.

Persistent microalbuminuria is the accepted marker for early detection of a high risk of developing diabetic nephropathy in patients diagnosed with Type I Diabetes mellitus. The Ambulatory Blood Pressure Monitoring (ABPM) evaluates the circadian variations of blood pressure while awake and asleep.

To show the renal function characteristics and the data provided by ABPM in a cohort of insulin dependent diabetic children referred to our hospital.

A total of 61 patients with an age range between 6 and 17 years were studied. In each child blood pressure monitoring was arranged, the glomerular filtration rate in 24 hour urine was estimated, and glycosylated haemoglobin (HbA1c), total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, was measured.

None of the cases showed persistent microalbuminuria. The renal function showed an increase in the glomerular filtration rate (146.6 ±22 ml/minute/1.73 m(2)). In 39% of the cases there was no drop in systolic blood pressure during the night, whereas 11% of the patients in our series had a decrease in diastolic pressure. The cases were analysed depending on whether or not there had been a physiological arterial or diastolic pressure drop during the night: there were no significant differences in anthropometric data, glycosylated haemoglobin (HbA1c) levels, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, glomerular filtration rate (GFR), proteinuria and microalbuminuria between both groups.

In Type I Diabetes Mellitus a decrease in the physiological blood pressure during the night is a frequent finding. There is also an increase in the glomerular filtration rate.

The objective of this study was to assess the frequency of microalbuminuria and the relationship with other risk factors for the development of diabetic nephropathy.

Our cross-section study involved a group of 60 adolescence of both sexes, mean age 15.3 ±2.43 years with mean duration of diabetes 7.74 ±3.44 years. Albumin excretion rate was measured on 2-3 samples of the first morning urine in the period below 6 months and persistent microalbuminuria was defined if its increased in two out of three urine specimens. Ambulatory blood pressure was monitored (ABPM, SpaceLabs 90207).

Microalbuminuria developed in 13.3% of adolescents with mostly completed sexual development, statistically significantly poorer metabolic control (9.79% vs. 8.7%) and higher BMI (23.59 kg/m(2) vs. 20.85 kg/m(2)) than in the patients with normoalbuminuria. The mean night-time systolic blood pressure (SBP) was statistically significantly higher in microalbuminuric patients than in normoalbuminurics. The nocturnal dip was reduced in 41.7% of our patients; 38.5% of nondippers were in normoalbuminuric and 62.5% in microalbuminuric patients.

Diabetic adolescents require particular attention in order to minimize the factors such as high HbA(1c), elevated body mass index and night-time SBP in the development of incipient nephropathy.

Twenty-four hour ambulatory blood pressure (ABPM) is emerging as a valuable tool to assess blood pressure (BP) changes in children with type 1 diabetes mellitus (DM1). Hypertension (HTN) is an important risk factor for, and may be an important indicator of diabetic nephropathy. Early accurate identification of HTN in DM1 may improve outcomes.

To evaluate BP in adolescents with DM1 using 24-hour ABPM, and to identify risk factors associated with abnormal blood pressure.

The ABPM of 105 children with DM1 was reviewed. Mean systolic BP (sBP) percentile was determined from the National High Blood Pressure Education Program (NHBPEP) tables. The patients with abnormal sBP were compared to those with normal sBP with respect to age, race, sex, body mass index (BMI) percentile, duration of DM1, average hemoglobin A1c (HbA1c) over the preceding year, and family history of hypertension.

Mean sBP was normal in 71%, whereas 23% had pre-hypertension, and 6% had stage 1 hypertension. Those who had abnormal sBP (pre-hypertension and stage 1 hypertension) had higher HbA1c (p = 0.023) and were more likely to be male (p = 0.03) than those with normal sBP.

Stage 1 hypertension is present in 6%, and pre-hypertension in 23% of adolescents with DM1. Poor diabetes control and male gender appear to be risk factors for abnormal sBP as measured by 24-hour ambulatory blood pressure monitoring.

To evaluate the diagnostic efficacy of the office blood pressure (OBP) and ambulatory blood pressure monitoring (ABPM) in the assessment of hypertension (HTN) in children with diabetes mellitus type 1 (T1DM).

We analyzed OBP and ABPM measurements in 84 diabetic children (43 boys) obtained at a median age of 14.9 yr and 6.3 +/- 3.5 yr after diagnosis of T1DM. OBP and ABPM results were converted into standard deviation scores (SDS). In addition, we analyzed blood pressure loads and nighttime dipping. The comparison between OBP and ABPM was performed using kappa coefficient and receiver operator curve (ROC).

HTN was diagnosed in 43/84 (51%) patients using OBP (>95th percentile), and in 24/84 (29%) patients using ABPM ( > or = 95th percentile during 24 h, day or night). Both methods were in agreement in 33 ABPM normotensive and 16 ABPM hypertensive patients (most had nighttime HTN); 32% patients had white-coat HTN and 9.5% patients had masked HTN. The kappa coefficient was 0.175 (95% CI from -0.034 to 0.384) suggesting poor agreement between OBP and ABPM. Diastolic OBP was a better predictor of ABPM HTN (ROC area under the curve (AUC) = 0.71 +/- 0.06) than systolic OBP (AUC = 0.58 +/- 0.07). The percentage of non-dippers ranged from 7 to 23% in ABPM normotensive patients, and 21-42% in ABPM hypertensive patients who also had significantly higher BP loads (p < 0.0001).

Children with T1DM often suffer from nocturnal, white coat- and masked HTN, which can not be assessed and predicted by the OBP.

A non-dipping pattern in ambulatory blood pressure monitoring (ABPM) increases the risk of cardiovascular disease. The association between renal function and the dipping pattern has not been studied in a random middle-aged population. This is a cross-sectional population-based study of 226 males and 234 females aged 40 to 62 years. Renal function was assessed with estimated glomerular filtration rate (eGFR). Non-dipping status was defined as a reduction of <10% between the daytime and the nighttime systolic BP. Non-dippers represented 18.7% of the study population. Their mean eGFR was 79.1 (s.d. 15.7) ml min(-1) per 1.73 m(2) as compared with a mean eGFR of 84.1 (s.d. 16.2) ml min(-1) per 1.73 m(2) in dippers (P=0.005); this difference remained significant after adjustments. Subjects in the lowest and in the middle eGFR tertiles had an independently increased risk of non-dipping in comparison with those in the highest eGFR tertile (odd ratios (OR), 2.34 (95% confidence interval (CI), 1.18 to 4.63) and OR, 2.01 (95% CI, 1.06 to 3.83), respectively). This study showed that even a minor deterioration in renal function is associated with increased risk of non-dipping pattern in ABPM in a random middle-aged population.

Hypertension in pediatric renal transplants is a widespread condition associated with high mortality risk in early adult life. Ambulatory blood pressure monitoring (ABPM) was found to be superior to office blood pressure (BP) in identifying true hypertensive and responders to treatment. The aim of this study was to investigate the role of repeated ABPM, performed at yearly intervals following transplantation, in the assessment and decision-making processes of post-transplant hypertension.

Thirty-seven recipients (23 males; aged 10.5 +/- 4.3 years) who were followed for 4.3 +/- 2.2 years (range 2-9) after transplantation were eligible for analysis. The mean follow-up time between the baseline (1 year post-transplantation) and the most recent ABPM examination was 3.3 +/- 2.2 years (range 1-8).

Throughout the follow-up period, antihypertensive therapy was either started or intensified in 27 recipients. These interventions were decided based on ABPM results obtained on 40 of 44 occasions. At last follow-up, 24 of 29 treated hypertensive recipients displayed controlled BP. This figure was significantly higher compared to our historical hypertensive control recipients in whom ABPM was applied for the first time in treatment at 6 +/- 3.3 years (range 2-15) after transplantation, while therapeutic decisions were driven by office BP measurements (95 % confidence interval (95% CI) for the difference between proportions (80.6-32 %) 36-60 %, P = 0.001).

Our study shows that, in a population with high risk for hypertension, repeated ABPM may significantly help to improve BP control.

Type 1 diabetes mellitus (T1DM) commonly occurs in childhood or adolescence, although the rising prevalence of type 2 diabetes mellitus (T2DM) in these age groups is now being seen worldwide. Diabetic nephropathy (DN) develops in 15-20% of subjects with T1DM and in similar or higher percentage of T2DM patients, causing increased morbidity and premature mortality. Although overt DN or kidney failure caused by either type of diabetes are very uncommon during childhood or adolescence, diabetic kidney disease in susceptible patients almost certainly begins soon after disease onset and may accelerate during adolescence, leading to microalbuminuria or incipient DN. Therefore, all diabetics warrant ongoing assessment of kidney function and screening for the earliest manifestations of renal injury. Pediatric health care professionals ought to understand about risk factors, strategy for prevention, method for screening, and treatment of early DN. This review considers each form of diabetes separately, including natural history, risk factors for development, screening for early manifestations, and strategy recommended for prevention and treatment of DN in children and adolescents.

Increased glomerular filtration rate (GFR) has been implicated in the development of diabetic nephropathy. Large normal interindividual variations of GFR hamper the diagnosis of renal hemodynamic alterations. We examined renal functional reserve (RFR) in children with type 1 diabetes mellitus to assess whether hyperfiltration occurs. The renal hemodynamic response following dopamine infusion was examined in 51 normoalbuminuric diabetic children (7.7 +/- 3.6 years) with a mean duration of diabetes of 6.2 years and compared them with 34 controls. Mean baseline GFR in diabetic children did not differ from the control population (130.7 +/- 22.9 vs. 124.8 +/- 25 ml/min per 1.73 m(2)), whereas renal plasma flow was significantly lower (463.7 +/- 103.9 vs. 587.2 +/- 105 ml/min per 1.73 m(2), p < 0.001), and filtration fraction was increased (29 +/- 8 vs. 21 +/- 2%, p < 0.001), compared with controls. The mean RFR was lower (p < 0.001) than in control subjects (-0.77 +/- 23 vs. 21 +/- 8 ml/min per 1.73 m(2)). This study documents an increased filtration fraction and reduced or absent RFR in children with type 1 diabetes mellitus in the stage before apparent nephropathy. GFR values were within normal range. Although the reduced RFR and increased filtration fraction indicate the presence of hemodynamic changes, their relevance to the development of hyperfiltration and subsequent diabetic nephropathy remains unknown.

Diabetic nephropathy is a severe complication and few studies have described the early morphological changes over time. Two kidney biopsies were performed, within a 6-year interval, in 29 primarily normoalbuminuric patients, aged 24 years at the second biopsy. These were examined with light and electron microscopy. Glomerular filtration rate, and effective renal plasma flow were determined with inulin and para-aminohippurate clearances. Urinary albumin excretion rate and the 24 ambulatory blood pressure were determined. Ten patients had developed microalbuminuria and/or hypertension; of these, six were treated with antihypertensive medication for 2 years or more. Significant increases were found in night time diastolic blood pressure and decreases in systolic and diastolic dipping. The glomerular volume, mesangial volume, mesangial matrix volume fraction and foot process width increased significantly. The group that was treated later for complications had the worst long-term metabolic control, thicker basement membranes and larger mesangial matrix and volume at the first biopsy, than the persistent normoalbuminuric group. During the follow-up, the untreated group with complications and the persistent normoalbuminuric group showed an increase in morphological parameters, whereas no progression occurred in the treated patients who also improved their metabolic control. In conclusion, the morphological parameters deteriorated in the normoalbuminuric patients and in those with complications, but were unchanged in the small antihypertensive-treated group with improved metabolic control.

The relationship between urinary albumin excretion rate (AER) and elevated blood pressure (BP) is unclear as a cause-effect phenomenon in the development of diabetic nephropathy. The aim of this study was to examine the association between AER, HbA1c and BP in children with normoalbuminuria.

24-hour ambulatory BP assessment was performed in 78 children with type 1 diabetes mellitus (DM1), age mean +/- SD 13.4 +/- 2.7 yr, range 7.3-18.3 yr, DM1 duration mean +/- SD 6.6 +/- 2.9 yr, range 2.1-11.9 yr. Using generalised linear mixed models with systolic (SBP) and diastolic (DBP) blood pressure as dependent variables, the effects of AER and HbA1c were examined, adjusting for age, gender, DM1 duration and insulin dose.

Patients with high normal AER (7-20 microg/min) had higher SBP during daytime and night-time compared to the low normal AER (< or = 7 microg/min) (mean +/- SD 118.20 +/- 7.98 and 110.33 +/- 7.08 mm Hg, p = 0.02; mean +/- SD 108.76 +/- 9.21 and 100.20 +/- 7.75 mm Hg, p = 0.03, respectively). DBP was also higher both during day- and night-time when compared to the < or = 7 microg/min group (mean +/- SD 73.40 +/- 6.50 and 64.86 +/- 5.67 mm Hg, p = 0.002; mean +/- SD 62.50 +/- 6.75 and 56.30 +/- 5.56 mm Hg, p = 0.03 day- and night-time, respectively).

A rise in SBP and DBP is associated with increased levels of AER even within the normal range.

Predictors of albumin excretion rate (AER) abnormalities could provide earlier indicators of diabetic nephropathy risk. Data from the Natural History Study, a prospective 5-year observation of renal structure and function in young type 1 diabetic patients, were examined for predictors of AER patterns in normoalbuminuric type 1 diabetic patients. Included were 170 patients (96 females) (aged 16.7 +/- 5.9 years, duration of diabetes 8.0 +/- 4.3 years) with normal blood pressure, normoalbuminuria (AER <20 microg/min), and eight or more follow-up visits over 5 years. AER, blood pressure, and HbA1c (A1C) were determined quarterly and glomerular filtration rate (GFR) annually. Persistent microalbuminuria (PMA) was defined as 20-200 microg/min in two of three consecutive values within 6-12 months. Four different AER patterns were identified. Group 1 (n = 99): all values <20 microg/min. Group 2 (n = 49): intermittent levels >20 microg/min but not meeting microalbuminuria criteria. Group 3 (n = 14): PMA during follow-up but normoalbuminuria at study exit. Group 4 (n = 8): microalbuminuria at study exit. Group 4 (497 +/- 95 nm, P < 0.01) and group 3 (464 +/- 113 nm, P = 0.03) patients had greater baseline glomerular basement membrane (GBM) width versus group 1 (418 +/- 67 nm). Baseline GFR in group 4 (163 +/- 37 ml.min(-1). 1.73 m(-2)) was higher than group 1 (143 +/- 28 ml.min(-1) . 1.73 m(-2), P = 0.04). A1C was higher in group 2 (9.0 +/- 1.2%) than group 1 (8.4 +/- 1.1%, P = 0.008). Thus, greater increases in GBM width and GFR were predictors of PMA. Since 64% of the patients that developed microalbuminuria reverted to normoalbuminuria, the risk of diabetic nephropathy as defined by current microalbuminuria criteria is unclear.

We compared renal morphology in normoalbuminuric adolescents with type 1 diabetes with age-and sex-matched controls. Renal morphological measurements in 46 unselected adolescents with diabetes for approx. 10 years were compared with those in 20 healthy kidney donors. Renal volume estimated by ultra-sound, renal function determined by clearances of inulin and para-aminohippurate, and long-term mean HbA(1c) were measured in the patient group. Basement membrane thickness (BMT), mesangial matrix and capillary volume fractions per glomerulus [V(V)(matrix/glom), V(V)(cap/glom)] were significantly greater in patients than in controls (505 nm, 10.5%, 46.7% vs. 320 nm, 7.9% and 39.3%). The foot processes were wider in patients than in living donors (414 nm vs. 372 nm). There was no difference in mean kidney volume of patients with diabetes and healthy subjects. Glomerular filtration rate, body weight, and slit pore length density explained 60% of the variance in renal volume. After about 10 years' duration of type 1 diabetes, BMT, V(V)(matrix/glom), V(V)(cap/glom), and foot process width were greater in normoalbuminuric adolescents than in healthy controls. This increase in foot processes of normoalbuminuric patients has not been reported before.