scholarly journals Hyperuricemia Is an Early and Relatively Common Feature in Children with HNF1B Nephropathy but Its Utility as a Predictor of the Disease Is Limited

2021 ◽  
Vol 10 (15) ◽  
pp. 3265
Author(s):  
Marcin Kołbuc ◽  
Beata Bieniaś ◽  
Sandra Habbig ◽  
Mateusz F. Kołek ◽  
Maria Szczepańska ◽  
...  
Keyword(s):  
Renal Function ◽  
Parathyroid Hormone ◽  
Strong Association ◽  
Fractional Excretion ◽  
National Registry ◽  
Multivariate Logistic Regression Model ◽  
Hepatocyte Nuclear Factor ◽  
Anthropometric Parameters ◽  
Renal Malformations ◽  
Reliable Marker

Background: Hyperuricemia is recognized as an important feature of nephropathy, associated with a mutation in the hepatocyte nuclear factor-1B (HNF1B) gene, and could serve as a useful marker of the disease. However, neither a causal relationship nor its predictive value have been proven. The purpose of this study was to assess this in children with renal malformations, both with (mut+) and without HNF1B mutations (mut-). Methods: We performed a retrospective analysis of clinical characteristics of pediatric patients tested for HNF1B mutations, collected in a national registry. Results: 108 children were included in the study, comprising 43 mut+ patients and 65 mut- subjects. Mean sUA was higher and hyperuricemia more prevalent (42.5% vs. 15.4%) in HNF1B carriers. The two groups were similar with respect to respect to age, sex, anthropometric parameters, hypertension, and renal function. Renal function, fractional excretion of uric acid and parathyroid hormone level were independent predictors of sUA. The potential of hyperuricemia to predict mutation was low, and addition of hyperuricemia to a multivariate logistic regression model did not increase its accuracy. Conclusions: Hyperuricemia is an early and common feature of HNF1B nephropathy. A strong association of sUA with renal function and parathyroid hormone limits its utility as a reliable marker to predict HNF1B mutation among patients with kidney anomalies.

scholarly journals MO043HYPERURICEMIA IS RELATIVELY COMMON IN CHILDREN WITH HNF1B MUTATION, BUT ITS UTILITY AS A CLINICALLY USEFUL MARKER FOR PREDICTING THE MUTATION IS LIMITED

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Marcin Kołbuc ◽  
Beata Bieniaś ◽  
Sandra Habbig ◽  
Mateusz Kołek ◽  
Maria Szczepanska ◽  
...  
Keyword(s):  
Uric Acid ◽  
Glucose Metabolism ◽  
Information Gain ◽  
Fractional Excretion ◽  
National Registry ◽  
Multicystic Dysplastic Kidney ◽  
Molecular Defect ◽  
Glucose Metabolism Disorders ◽  
Dysplastic Kidney ◽  
Renal Malformations

Abstract Background and Aims Hyperuricemia is recognized as an important feature of HNF1B nephropathy, and could serve as a good marker of the disease facilitating selection of patients for genetic testing. However, neither the casual relationship nor its predictive value have been proven yet. We thus decided to assess this in a cohort of children with renal malformations with (mut+) and without HNF1B mutations (mut-). Method We performed a retrospective analysis of clinical and genetic results of pediatric patients tested for HNF1B mutations, whose data were collected in a national registry. Hyperuricemia was assessed by using the newest, age- and gender-dependent reference values for serum uric acid (sUA) in children. Results A total of 108 children were included into the study comprising 43 mut+ patients, and 65 mut- subjects. Mean sUA was higher in mut+ than in mut- subjects (p = 0.006), and hyperuricemia was more prevalent in those with HNF1B mutations (42.5% vs. 15.4%, p = 0.002). Renal phenotype analysis revealed renal hyperechogenicity and multicystic dysplastic kidney disease were more frequent in mut+ patients, but no influence of any renal features/phenotypes on hyperuricemia was found. The two patient cohorts were different with regard to pancreatic anomaly (p < 0.001), glucose metabolism disorders (p = 0.003), hypomagnesemia (p < 0.001), and hyperparathyroidism (p < 0.001). In a multivariate linear stepwise regression model, eGFR, fractional excretion of uric acid, impairments in glucose metabolism and pancreatic anomaly were found to be independent predictive variables of sUA (R2=0.67, F=13.27, p < 0.001). Mutation was not identified as a determinant of sUA. After exclusion of patients with hyperglycemia and/or pancreatic malformations, the difference in hyperuricemia prevalence did not persist between mut+ and mut-. Potential of hyperuricemia for mutation prediction was tested in a model with hypomagnesemia and hyperparathyroidism, which showed an accuracy of 85% (sensitivity: 83%, specificity: 86%). Adding hyperuricemia to the model did not increase the accuracy (79%; sensitivity: 77%, specificity: 82%). Information gain, which informs selective potential of each parameter, was the lowest for hyperuricemia (0.34 compared with 0.99 and 0.63 for hyperparathyroidism and hypomagnesemia, respectively). Conclusion Hyperuricemia is relatively common in children with HNF1B mutation, however its direct association with this molecular defect remains still unproven. Its dependence on renal function and hyperglycemia diminishes the utility as a clinically useful marker for predicting HNF1B disease.

Iron-based phosphorus chelator: Risk of iron deposition and action on bone metabolism in uremic rats

2021 ◽  
pp. 153537022110572
Author(s):  
Wander Barros do Carmo ◽  
Bárbara Bruna Abreu Castro ◽  
Luísa Cardoso Manso ◽  
Priscylla Aparecida Vieira do Carmo ◽  
Clóvis Antônio Rodrigues ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Parathyroid Hormone ◽  
Calcium Carbonate ◽  
Kidney Disease ◽  
Therapeutic Option ◽  
Fractional Excretion ◽  
Control Group ◽  
Clinical Settings ◽  
Iron Based

Phosphate chelators are frequently used in patients with chronic kidney disease (CKD). New iron-based chelators remain understudied and offer a promising therapeutic option for the control of bone and mineral disorders of chronic kidney disease (BMD-CKD). We assessed the effect of the phosphorus chelator, chitosan-iron III (CH-FeCl), compared to calcium carbonate (CaCO3) in BMD-CKD and the potential iron overload in uremic rats. Thirty-two animals were divided into four groups, namely the control, CKD, CKD/CH-FeCl, and CKD/CaCO3 groups. CKD was induced by adding 0.75% (4 weeks) and 0.1% (3 weeks) adenine to the diet. The chelators were administered from week 3 through week 7. The renal function, BMD-CKD markers, and histomorphometry of the femur were assessed at week 7. The CKD group showed a significant increase in creatinine (83.9 ± 18.6 vs. 41.5 ± 22.1 µmol/L; P = 0.001), phosphate (3.5 ± 0.8 vs. 2.2 ± 0.2 mmol/L; P = 0.001), fractional excretion of phosphorus (FEP) (0.71 ± 0.2 vs. 0.2 ± 0.17; P = 0.0001), and FGF23 (81.36 ± 37.16 pg/mL vs. 7.42 ± 1.96; P = 0.011) compared to the control group. There was no accumulation of serum or bone iron after the use of CH-FeCl. The use of chelators reduced the FEP (control: 0.71 ± 0.20; CKD/CH-FeCl: 0.40 ± 0.16; CKD/CaCO3 0.34 ± 0.15; P = 0.001), without changes in the serum FGF23 and parathyroid hormone levels. Histomorphometry revealed the presence of bone disease with high remodeling in the uremic animals without changes with the use of chelators. The CH-FeCl chelator was efficient in reducing the FEP without iron accumulation, thereby paving the way for the use of this class of chelators in clinical settings in the future.

scholarly journals Advances in the diagnosis and the management of primary hyperparathyroidism

2021 ◽  
Vol 12 ◽  
pp. 204062232110159
Author(s):  
Ana Kashfia Islam
Keyword(s):  
Renal Function ◽  
Parathyroid Hormone ◽  
Bone Loss ◽  
Primary Hyperparathyroidism ◽  
Kidney Stones ◽  
Parathyroid Glands ◽  
Definitive Treatment ◽  
Indications For Surgery ◽  
Musculoskeletal Complaints ◽  
Parathyroid Cancer

The parathyroid glands, one of the last organs to be discovered, are responsible for maintaining calcium homeostasis, and they continue to present the clinician with diagnostic and management challenges that are reviewed herein. Primary hyperparathyroidism (PHPT) comprises the vast majority of pathology of the parathyroid glands. The classic variant, presenting with elevated calcium and parathyroid hormone levels, has been studied extensively, but the current body of literature has added to our understanding of normocalcemic and normohormonal variants of PHPT, as well as syndromic forms of PHPT. All variants can lead to bone loss, kidney stones, declining renal function, and a variety of neurocognitive, gastrointestinal, and musculoskeletal complaints, although the majority of PHPT today is asymptomatic. Surgery remains the definitive treatment for PHPT, and advances in screening, evolving indications for surgery, new imaging modalities, and improvements in intra-operative methods have greatly changed the landscape. Surgery continues to produce excellent results in the hands of an experienced parathyroid surgeon. For those patients who are not candidates for surgery, therapeutic advances in medical management allow for improved control of the hypercalcemic state. Parathyroid cancer is extremely rare; the diagnosis is often made intra-operatively or on final pathology, and recurrence is common. The mainstay of treatment is normalization of serum calcium via surgery and medical adjuncts.

Enhanced renal sensitivity of the spontaneously hypertensive rat to urotensin II

2008 ◽  
Vol 295 (4) ◽  
pp. F1239-F1247 ◽  
Author(s):  
Alaa E. S. Abdel-Razik ◽  
Richard J. Balment ◽  
Nick Ashton
Keyword(s):  
Renal Function ◽  
Spontaneously Hypertensive Rat ◽  
Renal Medulla ◽  
Fractional Excretion ◽  
Urotensin Ii ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Hypertensive Rat ◽  
Fractional Excretion Of Sodium ◽  
Wistar Kyoto

Urotensin II (UII) has been implicated widely in cardiovascular disease. The mechanism(s) through which it contributes to elevated blood pressure is unknown, but its emerging role as a regulator of mammalian renal function suggests that the kidney might be involved. The aim of this study was to determine the effect of UII on renal function in the spontaneously hypertensive rat (SHR). UII infusion (6 pmol·min−1·100 g body wt−1) in anesthetized SHR and control Wistar-Kyoto (WKY) rats produced marked reductions in glomerular filtration rate (ΔGFR WKY, n = 7, −0.3 ± 0.1 vs. SHR, n = 7, −0.6 ± 0.1 ml·min−1·100 g body wt−1, P = 0.03), urine flow, and sodium excretion rates, which were greater in SHR by comparison with WKY rats. WKY rats also showed an increase in fractional excretion of sodium (ΔFENa; +0.6 ± 0.1%, P = 0.02) in contrast to SHR in which no such change was observed (ΔFENa −0.6 ± 0.2%). Blockade of the UII receptor (UT), and thus endogenous UII activity, with urantide evoked an increase in GFR which was greater in SHR (+0.3 ± 0.1) compared with WKY rats (+0.1 ± 0.1 ml·min−1·100 g body wt−1, P = 0.04) and was accompanied by a diuresis and natriuresis. UII and UT mRNA expression were greater in the renal medulla than the cortex of both strains; however, expression levels were up to threefold higher in SHR tissue. SHR are more sensitive than WKY to UII, which acts primarily to lower GFR thus favoring salt retention in this model of hypertension.

Comparison of the effects of parathyroid hormone (PTH) and recombinant PTH-related protein on bicarbonate excretion by the isolated perfused rat kidney

1990 ◽  
Vol 126 (3) ◽  
pp. 403-408 ◽  
Author(s):  
A. G. Ellis ◽  
W. R. Adam ◽  
T. J. Martin
Keyword(s):  
Parathyroid Hormone ◽  
Rat Kidney ◽  
Urine Volume ◽  
Clinical Manifestations ◽  
Fractional Excretion ◽  
Bicarbonate Concentration ◽  
Isolated Perfused Rat Kidney ◽  
Amino Terminal ◽  
Fractional Excretion Of Sodium ◽  
Perfused Rat Kidney

ABSTRACT The isolated perfused rat kidney was used to study the effects of amino-terminal fragments of human parathyroid hormone, hPTH(1–34), bovine parathyroid hormone, bPTH(1–84) and of PTH-related proteins, PTHrP(1–34), PTHrP(1–84), PTHrP(1–108) and PTHrP(1–141) on urinary bicarbonate excretion. PTHrP(1–34) (7 nmol/l), bPTH(1–84) (5·5 nmol/l) and hPTH(1–34) (7 nmol/l) had similar effects in increasing bicarbonate excretion with respect to the control. At lower concentrations (0·7 nmol/l) all PTHrP components, but not hPTH(1–34) or bPTH(1–84) increased bicarbonate excretion significantly. Infusions of PTHrP(1–108) and PTHrP(1–141) at 0·7 nmol/l, while associated with a rise in urinary bicarbonate concentration and excretion during the early stages of perfusion, produced a sharp decline in bicarbonate concentration and excretion in the latter part of perfusion. The different peptides produced no significant differences in glomerular filtration rate, fractional excretion of sodium or urine volume. The absence of substantial differences between the effects of hPTH(1–34) and PTHrP(1–34) are as noted in previous studies. The differences between PTHrP(1–108)/PTHrP(1–141) and PTHrP(1–34) demonstrated here are consistent with (1) the clinical manifestations of acidosis in hyperparathyroidism and alkalosis in humoral hypercalcaemia of malignancy, and (2) an independent action of a component of PTHrP beyond amino acids 1–34. Journal of Endocrinology (1990) 126, 403–408

scholarly journals Dopamine enhances the phosphaturic response to parathyroid hormone in phosphate-deprived rats.

1992 ◽  
Vol 2 (9) ◽  
pp. 1423-1429
Author(s):  
J Isaac ◽  
T J Berndt ◽  
S L Chinnow ◽  
G M Tyce ◽  
T P Dousa ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Fractional Excretion ◽  
Phosphate Transport ◽  
Dopamine Synthesis ◽  
Dopamine Infusion ◽  
Phosphate Deprivation ◽  
Dietary Phosphate ◽  
Urinary Dopamine ◽  
Fractional Excretion Of Phosphate ◽  
High Phosphate

Phosphate deprivation results in a resistance to the phosphaturic effect of parathyroid hormone. Dopamine is phosphaturic and is synthesized by kidney proximal tubule, the nephron subsegment where parathyroid hormone inhibits phosphate transport. Thus, to test the hypothesis that phosphate deprivation is associated with low intrarenal dopamine synthesis and that dopamine infusion will overcome the resistance to the phosphaturic response to parathyroid hormone, the following study was performed. The effect of dietary phosphate intake on intrarenal dopamine synthesis, as reflected by urinary dopamine excretion, was determined. Rats were placed in metabolic cages (N = 5) and were fed a low-phosphate diet (0.07% Pi) for 4 days and then a high-phosphate diet (1.8% Pi) for 4 days. Twenty-four-hour urinary dopamine excretion was significantly lower in rats fed a low-phosphate diet (2.53 +/- 0.06 versus 4.10 +/- 0.30 micrograms/day). Further, the effect of dopamine infusion on the blunted phosphaturic response to parathyroid hormone was studied in rats fed a low-phosphate diet for 1, 2, and 3 days. Control clearances were taken 2 h after thyroparathyroidectomy; then, parathyroid hormone (33 U/kg plus 1 U/kg/min), dopamine (25 micrograms/kg/min), or parathyroid hormone plus dopamine were infused for 60 min. Changes in the fractional excretion of phosphate were significantly greater in rats fed a low-phosphate diet infused with parathyroid hormone plus dopamine than in rats fed a low-phosphate diet infused with parathyroid hormone alone (delta 27.9 +/- 5.8 versus 11.2 +/- 2.6% for day 1; 28.4 +/- 1.4 versus 7.1 +/- 3.6% for day 2; and 10.7 +/- 2.8 versus -0.2 +/- 0.2% for day 3; N = 5 for all groups).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Interaction between serum FGF-23 and PTH in renal phosphate excretion, a case-control study in hypoparathyroid patients

2019 ◽  
Author(s):  
Forough Saki ◽  
Seyed Reza Kassaee ◽  
Azita Salehifar Salehifar ◽  
gholamhossein Ranjbar omrani
Keyword(s):  
Parathyroid Hormone ◽  
Serum Calcium ◽  
Case Control Study ◽  
Fractional Excretion ◽  
Case Control ◽  
Control Group ◽  
Phosphate Excretion ◽  
Significant Difference ◽  
Fgf 23 ◽  
Control Study

Abstract Background:phosphate homeostasis is mediated through complex counter regulatory feed-back balance between parathyroid hormone, FGF-23 and 1,25(OH)2D. Both parathyroid hormone and FGF-23 regulate proximal tubular phosphate excretion through signaling on sodium- phosphate cotransporters II a and II c . However, the interaction between these hormones on phosphate excretion is not clearly understood. We performed the present study to evaluate whether the existence of sufficient parathyroid hormone is necessary for full phosphaturic function of FGF-23 or not. Methods:In this case-control study, 19 patients with hypoparathyroidism and their age- and gender-matched normal population were enrolled. Serum calcium, phosphate, alkaline phosphatase,parathyroid hormone, FGF-23, 25(OH)D, 1,25(OH)2D and Fractional excretion of phosphorous were assessed and compared between the two groups, using SPSS software. Results:The mean serum calcium and parathyroid hormone level was significantly lower in hypoparathyroid patients in comparison with the control group(P<0.001 and P<0.001, respectively). We found high serum level of phosphate and FGF-23 in hypoparathyroid patients compared to the control group (P<0.001 and P<0.001,respectively). However, there was no significant difference in Fractional excretion of phosphorous or 1,25OH2D level between the two groups. There was a positive correlation between serum FGF-23 and Fractional excretion of phosphorous just in the normal individuals (P <0.001, r = 0.79). Conclusions:Although the FGF-23 is a main regulator of urinary phosphate excretion but the existence of sufficient parathyroid hormone is necessary for the full phosphaturic effect of FGF-23.

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