Kidney volume, kidney function, and ambulatory blood pressure in children born extremely preterm with and without nephrocalcinosis

BackgroundUnlicensed medications are used all the time in the management of diseases in childhood. Tolvaptan (Jinarc®) is a vasopressin V2-receptor antagonist licensed for use to slow the progression of cyst development and renal insufficiency of ADPKD in adults with CKD stage 1 to 3 with evidence of rapidly progressing disease. Studies of animal models implicate the antidiuretic hormone arginine vasopressin and its messenger cyclic adenosine monophosphate (cAMP) as promoters of kidney-cyst cell proliferation and luminal fluid secretion. The suppression of vasopressin release by means of high water intake, genetic elimination of vasopressin, and vasopressin V2-receptor blockade all reduce the cyst burden and protect kidney function1 A Phase 3 trial showed that Tolvaptan, as compared with placebo, slowed down the increase in total kidney volume and decline in kidney function in adults (average 39 yrs) with ADPKD over a 3-year period.2 ADPKD is the most common form of polycystic kidney disease (PKD) typically late in onset and results from mutation of either of two genes: PKD1 and PKD2. Autosomal recessive polycystic kidney (ARPKD), the other form of PKD, is 20 times less common, presents primarily in infancy and childhood, is typically more severe, and commonly associated with hypertension. ARPKD results from mutation of PKHD1. In spite of these differences, there is growing evidence to suggest that ADPKD and ARPKD are more related than previously suspected.3 Bilineal inheritance of PKD1 abnormalities has been reported to cause extremely severe disease resembling ARPKD.4 The use of Tolvaptan in the management of PKD in children is therefore expected to become more important.AimTo describe the first known UK use of Tolvaptan in a neonate with severe ADPKD and the role of the hospital pharmacist in facilitating the use.MethodThe role descriptor of hospital pharmacists produced by the World Health Organisation (WHO) was adapted and used to map the pharmaceutical challenges of using Tolvaptan in this child. The descriptor include: (i) Promotion of rational prescribing of drugs, (ii) Use of specialist pharmacists networks to gain greater expertise; (iii) Monitor compliance and therapeutic response and report adverse drug reactions; (iv) ensure supply of high quality products; (v) partake in planning and implementation of clinical trials.ResultsThe use of Tolvaptan for indication other than hyponatraemia and other endocrine uses are not routinely commissioned by NHS England. In view of the exceptionality of this case – a severe neonatal form of ADPKD with estimated prevalence of the order of 1 in tens of millions, an Individual Funding Request (IFR) application was made and was approved. The application was supported by financial information provided by the hospital pharmacist who facilitated the application process. Using available information and formulation knowledge, a suspension was eventually recommended and was well tolerated. This resulted in approximately 85% reduction in the cost of treatment over six months. Tolvaptan produced the expected aquaresis and blood pressure reduction. Initial dose of 0.1 mg/kg/day was used and increased according to weight and clinical response. Initial monitoring parameters, which included 4 hourly blood pressure, urine and electrolytes and hepatic function, were recommended. Electrolyte supplements were adjusted accordingly. At 2-month review point, there was no oedema of leg and face but the kidneys were still enlarged. The long term effect on cyst burden and kidney function is being evaluated and will feed into the IFR process.ConclusionThe use of unlicensed medications in children poses a number of pharmaceutical challenges and can be managed through a multidisciplinary approach to treatment intervention. It also re-enforce the paediatric formulation challenge to pharmaceutical companies in which formulation needs are prioritised and existing data are better used to facilitate paediatric formulation development.

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Genetic variants associated with adult blood pressure and kidney function do not affect fetal kidney volume. The Generation R Study

Early Human Development ◽

10.1016/j.earlhumdev.2012.02.014 ◽

2012 ◽

Vol 88 (9) ◽

pp. 711-716 ◽

Cited By ~ 1

Author(s):

H. Rob Taal ◽

Leontine C.L. van den Hil ◽

Albert Hofman ◽

Albert J. van der Heijden ◽

Vincent W.V. Jaddoe

Keyword(s):

Blood Pressure ◽

Kidney Function ◽

Genetic Variants ◽

Kidney Volume ◽

Fetal Kidney

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Association between nocturnal blood pressure dipping and chronic kidney disease among patients with controlled office blood pressure

American Journal of Hypertension ◽

10.1093/ajh/hpab031 ◽

2021 ◽

Author(s):

So Mi J Cho ◽

Hokyou Lee ◽

Tae-Hyun Yoo ◽

Jong Hyun Jhee ◽

Sungha Park ◽

...

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Systolic Blood Pressure ◽

Kidney Function ◽

Ambulatory Blood Pressure ◽

Office Blood Pressure ◽

Nocturnal Blood Pressure ◽

Blood Pressure Dipping ◽

Nocturnal Blood Pressure Dipping

Abstract Background Although abnormal blood pressure patterns are associated with adverse cardiorenal outcomes, their associations are yet unquantified by nocturnal dipping status. We examined the association of nocturnal blood pressure dipping pattern with albuminuria and kidney function among participants with controlled hypertension without prior advanced kidney disease. Methods Ambulatory blood pressure measurements were collected from 995 middle-aged, cardiology clinic patients with controlled office blood pressure (<140/90 mmHg). The magnitude of dipping was calculated as the difference between daytime and nighttime systolic blood pressure divided by daytime systolic blood pressure. Accordingly, the participants were categorized as extreme-dipper (≥20%), dipper (10-<20%), non-dipper (0-<10%), or reverse-dipper (<0%). We analyzed the cross-sectional associations of dipping with albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g) and decreased estimated glomerular filtration rate (<60 ml/min/1.73m 2), adjusting for office/ambulatory blood pressure, antihypertensive class, body mass index, total cholesterol, fasting glucose, socioeconomic status, and health behavior. Results The participants (mean age 60.2 years; 52.9% male) consisted of 13.5% extreme-dippers, 43.1% dippers, 34.7% non-dippers, and 8.7% reverse-dippers. In reference to dippers, odds ratios [95% confidence interval] for albuminuria were 1.73 [1.04-2.60] in reverse-dippers, 1.67 [1.20-2.32] in non-dippers, and 0.62 [0.38-1.04] in extreme-dippers. Likewise, abnormal dipping profile was associated with decreased kidney function: reverse-dipping, 2.02 [1.06-3.84]; non-dipping, 1.98 [1.07-3.08]; extreme-dipping, 0.69 [0.20-1.17]. The associations persisted participants with more conservatively controlled office blood pressure (<130/80 mmHg). Conclusions Monitoring diurnal and nocturnal blood pressure may identify chronic kidney disease otherwise overlooked based on office blood pressure.

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Risk factors for the development of diabetic nephropathy

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0902018a ◽

2009 ◽

Vol 137 (1-2) ◽

pp. 18-26 ◽

Cited By ~ 1

Author(s):

Miodrag Antic ◽

Aleksandra Jotic ◽

Milan Radovic ◽

Jelena Seferovic ◽

Nebojsa Lalic ◽

...

Keyword(s):

Diabetes Mellitus ◽

Blood Pressure ◽

Diabetic Nephropathy ◽

Kidney Function ◽

Kidney Volume ◽

Factors Associated ◽

Patients With Diabetes ◽

Dm Type 2

Introduction. Results of epidemiological analysis show that one third of patients with diabetes mellitus develop diabetic nephropathy (DN). Strategies used until now to slow down the progression of DN were initiated when the symptoms of DN were already present. Objective. Our objective was to analyze the prevalence and characteristics of DN and to determine the factors leading to DN. Methods. Fifty-two patients with diabetes mellitus (DM) - 32 with type 1 aged 32 years and 20 with type 2 aged 59 years - were referred from the Institute of Endocrinology, Diabetes and Metabolic Diseases to the Department of Nephrology for kidney function evaluation. Apart from routine laboratory analyses, glomerular filtration rate was calculated using the MDRD formula (modification of diet in renal disease), the size of the kidney was measured by ultrasound, and kidney volume was calculated using the ellipsoid formula. Results Thirty percent of the patients revealed normal (eight patients with DM type 1) or satisfactory kidney function (eight patients with DM type 1) with physiological proteinuria. Micro-albuminuria (MAU) or pathological proteinuria (PRT) were found in 10 and 9 patients, respectively, with DM type 1, while decreased kidney function was found in one patient without proteinuria. MAU or PRT were found in four and eight patients, respectively, with DM type 2 and decreased kidney function in four patients without proteinuria. Kidney function was significantly lower in patients with DM type 2 in comparison to DM type 1, while the patients with decreased kidney function had a higher PRT. Compared to DM type 2, in DM type 1 patients, the kidney was longer, and parenchymal artery resistance index was lower in DM type 1 patients compared to DM type 2. Factors associated with DN were patient's age, duration of diabetes, systolic blood pressure, HbA1c and kidney volume. Conclusion. The prevalence of DN among the studied patients was 70%. Treatable factors associated with the development of DN are strict control of blood pressure and glycaemia control.

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