scholarly journals Diagnostic Strategies to Identify Patients with Genetic Salt-Losing Tubulopathies

2021 ◽  
Author(s):  
Elizabeth Wan ◽  
Daniela Iancu ◽  
Emma Ashton ◽  
Keith Siew ◽  
Barian Mohidin ◽  
...  
Keyword(s):  
Classification Accuracy ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Bartter Syndrome ◽  
Diagnostic Strategies ◽  
Biochemical Variables ◽  
Pathogenic Variants ◽  
Simpler Algorithm ◽  
Observational Cohort ◽  
Renal Tubular

Background: Distinguishing patients with the inherited salt-losing tubulopathies (SLT), Gitelman or Bartter syndrome (GS or BS) from wildtype (WT) patients who purge is difficult. We decided to identify clinical/biochemical characteristics which correctly classify SLT. Methods: 66 patients with possible SLT were recruited to a prospective observational cohort study at the UCL Renal Tubular Clinic (London). 31 datapoints were recorded on each patient. All patients were genotyped for pathogenic mutations in genes which cause SLT; 39 patients had pathogenic variants in genes causing SLT. We obtained similar datasets from cohorts in Taipei and Kobe; the combined dataset comprised 419 patients, 291 had genetically confirmed SLT. London and Taipei datasets were combined to train machine learning (ML) algorithms. These were then tested on the Kobe dataset to determine the best biochemical predictors of genetic confirmation of SLT. Results: Single biochemical variables (e.g. plasma renin) were significantly, but inconsistently different between SLT and WT, in the London and combined cohorts. A decision table algorithm using serum bicarbonate and urinary sodium excretion (FENa) achieved a classification accuracy of 74%. A simpler algorithm based on the FECl achieved a classification accuracy of 61%. This was superior to all of the single biochemical variables identified previously.

Neurogenic regulation of rate of achieving sodium balance after increasing sodium intake

1991 ◽  
Vol 261 (2) ◽  
pp. F300-F307 ◽  
Author(s):  
S. G. Greenberg ◽  
S. Tershner ◽  
J. L. Osborn
Keyword(s):  
Sodium Intake ◽  
Plasma Renin ◽  
Sympathetic Nerves ◽  
Urinary Sodium Excretion ◽  
Significant Inhibition ◽  
Sodium Balance ◽  
Renal Nerves ◽  
High Sodium ◽  
Low Sodium ◽  
Renal Tubular

Evidence that the renal sympathetic nerves have direct effects on renal tubular function suggests that neurogenic mechanisms may play an important role in the daily regulation of sodium balance. We evaluated the influence of the renal nerves on the rate of elevating urinary sodium excretion (UNaV) after a step increase in fixed sodium intake. Conscious rats with innervated (INN) or denervated (DNX) kidneys were placed on low-sodium intake (LNa = 0.3 meq/day) or a normal sodium intake (NNa = 1.0 meq/day) by intravenous infusion. Hourly changes in UNaV were determined 24 h before and 72 h after increasing sodium intake to either NNa or high-sodium intake (HNa = 5.0 meq/day). Switching from LNa to NNa, INN rats increased UNaV within 24 h; however, DNX rats did not begin to increase UNaV until hour 60. Cumulative sodium balance over 72 h was more positive in DNX rats (INN = 1.29 +/- 0.29 meq; DNX = 2.06 +/- 0.21 meq, P less than 0.05). During the LNa-to-HNa switch, both INN and DNX rats increased UNaV equally for 12 h; however, at this time INN rats continued to increase UNaV, whereas DNX rats did not. DNX rats had a net accumulation of 2.54 meq more sodium than INN rats over 72 h. Significant inhibition of plasma renin activity within the first 24 h occurred only in rats receiving the LNa-to-HNa switch in sodium intake, and this response was not different between rats with innervated and denervated kidneys. These data suggest that the renal nerves provide a rapid sodium excretory response to step increases in sodium intake.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Gitelman syndrome and ectopic calcification in the retina and joints

2021 ◽  
Author(s):  
Yeji Ham ◽  
Heather Mack ◽  
Deb Colville ◽  
Philip Harraka ◽  
B Biomed ◽  
...  
Keyword(s):  
Calcium Pyrophosphate ◽  
Bartter Syndrome ◽  
Gitelman Syndrome ◽  
Ectopic Calcification ◽  
Aggressive Management ◽  
Renal Tubular Disorder ◽  
Rate Of Progression ◽  
Renal Tubular ◽  
Retinal Photography

ABSTRACT Gitelman syndrome is a rare inherited renal tubular disorder with features that resemble thiazide use, including a hypokalemic metabolic alkalosis, hypomagnesemia, hypocalciuria, a low or normal blood pressure, and hyperreninemia and hyperaldosteronism. Treatment is primarily correction of the K and Mg levels. The diagnosis is confirmed with genetic testing but Gitelman syndrome is often not suspected. However the association with ectopic calcification in the retina, blood vessels and chondrocalcinosis in the joints is a useful pointer to this diagnosis. Bilateral symmetrical whitish deposits of calcium pyrophosphate are visible superotemporally on ophthalmoscopy and retinal photography but are actually located beneath the retina in the sclerochoroid. Optical coherence tomography is even more sensitive for their detection. These deposits increase in size with time, but the rate of progression slows with long-term correction of the hypomagnesemia. Calcification may be complicated by atrophy of the overlying retina and visual loss. The deposits often correlate with ectopic calcification in the aorta, coronary and cerebral vessels. Chondrocalcinosis occurs in the large joints such as the knees. Ectopic calcification in Gitelman syndrome indicates the need for more aggressive management of Ca and Mg levels. Calcification is much less common in Bartter syndrome which itself is rarer and associated less often with hypomagnesemia.

Sex differences in prenatal programming of hypertension by dexamethasone

2021 ◽  
pp. 153537022110032
Author(s):  
Issa Alhamoud ◽  
Susan K Legan ◽  
Jyothsna Gattineni ◽  
Michel Baum
Keyword(s):  
Blood Pressure ◽  
Plasma Renin ◽  
Female Offspring ◽  
Male Offspring ◽  
Thick Ascending Limb ◽  
Protein Abundance ◽  
Female Rat ◽  
Prenatal Programming ◽  
Transporter Protein ◽  
Renal Tubular

Prenatal dexamethasone has been shown to increase blood pressure in male offspring but the mechanism for the increase in blood pressure is unclear. The present study examined if prenatal programming by maternal injection of dexamethasone on days 15 and 16 of gestation affected the blood pressure comparably in female and male offspring. Our hypothesis was that males would be affected by prenatal dexamethasone to a greater extent than females and that either an increase in renal tubular transporter abundance or an increase in renin or aldosterone system would be associated with hypertension with prenatal programming. Prenatal dexamethasone increased blood pressure at two months and six months of age and resulted in proteinuria and albuminuria at six months in male but not female rat offspring. There was no effect of prenatal dexamethasone on blood pressure and proteinuria at one month in male and in female offspring. While prenatal dexamethasone increased male renal thick ascending limb sodium potassium two chloride cotransporter protein abundance at two months, prenatal dexamethasone on days 15 and 16 of gestation did not affect transporter abundance in males at other ages, nor did it affect proximal tubule sodium/hydrogen exchanger or distal convoluted tubule sodium chloride cotransporter protein abundance at any age. There was no difference in systemic renin or aldosterone in the prenatal dexamethasone group compared to same sex controls. In conclusion, male but not female offspring have an increase in blood pressure and urinary protein excretion with prenatal dexamethasone. The increase in blood pressure with prenatal programming was not associated with a consistent increase in renal tubular transporter protein abundance, nor plasma renin activity and serum aldosterone.

Type-5 Bartter syndrome presenting with metabolic seizure in adulthood

2021 ◽  
Vol 14 (2) ◽  
pp. e235349
Author(s):  
Aqeel Hussain ◽  
Mahendra Atlani ◽  
Abhishek Goyal ◽  
Alkesh Kumar Khurana
Keyword(s):  
Age Of Onset ◽  
Bartter Syndrome ◽  
Electrolyte Imbalance ◽  
Thick Ascending Limb ◽  
Calcium Sensing Receptor ◽  
Inherited Disorders ◽  
Calcium Sensing ◽  
Aged Woman ◽  
Middle Aged Woman ◽  
Renal Tubular

Bartter syndrome is a very rare and heterogeneous disease with variable age of onset and symptom severity. Genotypically they have inherited disorders of the thick ascending limb in the renal tubular system, which manifest phenotypically as electrolyte imbalance due to loss of sodium, chloride and potassium. Gain of function mutations in the calcium-sensing receptor has been described in some patients with Bartter’s syndrome (type-5 Bartter syndrome or autosomal dominant hypocalcaemia with Bartter syndrome) associated with hypocalcaemia and hypercalciuria differentiating it from Gitelman syndrome. This phenotype has been reported to present in adulthood with metabolic abnormalities. We present a case of a middle-aged woman who presented with metabolic seizures and on evaluation was found to have profound electrolyte abnormalities which were corrected with supplements and led to the resolution of symptoms.

The renin-aldosterone system in pre-eclampsia, essential and transient hypertension during pregnancy, and normotensive pregnant and non-pregnant control subjects

1982 ◽  
Vol 101 (2) ◽  
pp. 273-280 ◽  
Author(s):  
E. B. Pedersen ◽  
A. B. Rasmussen ◽  
P. Johannesen ◽  
H. J. Kornerup ◽  
S. Kristensen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Third Trimester ◽  
Plasma Aldosterone Concentration ◽  
The Third ◽  
Control Subjects ◽  
Hypertension In Pregnancy ◽  
Normotensive Pregnancy ◽  
In Pregnancy

Abstract. Plasma renin concentration (PRC), plasma aldosterone concentration (PAC), and blood pressure were determined in the third trimester in pregnancy, 5 days and 6 months after delivery in pre-eclampsia, essential and transient hypertension in pregnancy and in normotensive pregnant and non-pregnant control subjects. PRC and PAC were elevated several fold above non-pregnant level in all groups during pregnancy. In pre-eclampsia PRC and PAC were 220 and 160%, respectively, above the levels 6 months after delivery, and thus lower than the corresponding values, 360 and 402%, in normotensive pregnancy. In essential and transient hypertension PRC and PAC increased to the same degree as during normotensive pregnancy. Urinary sodium excretion, serum sodium and creatinine clearance were reduced in pre-eclampsia, but not in essential and transient hypertension when compared to normotensive pregnant controls. All the parameters determined were the same as in non-pregnant controls 6 months after delivery in all groups. There were no correlations between blood pressure and PRC or PAC in any of the groups neither in pregnancy nor after delivery. It is concluded that the renin-aldosterone system is stimulated in lesser degree in pre-eclampsia than in both essential hypertension, transient hypertension and normotensive pregnancy, and there was no evidence for a causal relationship between the renin-aldosterone system and blood pressure neither in normotensive nor hypertensive pregnancy.

Are Racial Differences in Essential Hypertension Due to Different Pathogenetic Mechanisms?

1978 ◽  
Vol 55 (s4) ◽  
pp. 383s-386s ◽  
Author(s):  
P. S. Sever ◽  
W. S. Peart ◽  
T. W. Meade ◽  
I. B. Davies ◽  
D. Gordon ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Plasma Renin Activity ◽  
Racial Differences ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Renin Activity ◽  
Plasma Noradrenaline ◽  
Noradrenaline Concentration ◽  
Blacks And Whites ◽  
Made In

1. Plasma noradrenaline concentration and plasma renin activity were measured in a control, British, urban population (n = 115) in which blacks were matched for age and sex with whites. 2. Similar measurements were made in subjects with essential hypertension (77 white and 23 black), and 48 healthy normotensive white civil servants. 3. In controls blood pressure was significantly higher in blacks; it correlated with age in both races and with pulse rate in blacks. There were no significant racial differences in plasma noradrenaline which was positively correlated with age in both blacks and whites. Mean plasma renin activity was 55% lower in blacks, and this difference was not related to urinary sodium excretion. 4. In hypertensive subjects plasma noradrenaline positively correlated with age in blacks. This relationship was not found in whites in whom 20% of young hypertensive subjects (<45 years) had significantly raised plasma noradrenaline. Plasma renin activity was again significantly lower in blacks. In white hypertensives plasma noradrenaline and renin activity were significantly correlated. 5. There may be racial differences in the pathogenesis of essential hypertension.

Central effects of atrial natriuretic factor on renal salt excretion

1991 ◽  
Vol 261 (2) ◽  
pp. F354-F359 ◽  
Author(s):  
P. Rohmeiss ◽  
G. Demmert ◽  
T. Unger
Keyword(s):  
Sodium Excretion ◽  
Atrial Natriuretic Factor ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Renal Nerves ◽  
Urinary Flow ◽  
Renal Nerve ◽  
Ureteral Catheter ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

Atrial natriuretic factor (ANF) has been localized in periventricular brain areas involved in cardiovascular and fluid control. We investigated the effect of intracerebroventricular (icv) ANF (alpha-rat atriopeptin III) on renal sodium excretion in unilaterally nephrectomized, conscious unrestrained rats fitted with a chronic ureteral catheter. Isotonic NaCl (1 ml/h) was infused intravenously. ANF injected at doses (icv) of 1 ng (n = 6), 100 ng (n = 7), and 1 microgram (n = 7) reduced urinary sodium excretion (all values mumol/45 min, means +/- SE) from 111.6 +/- 24.4 to 83 +/- 20 (P less than 0.05), from 96.9 +/- 25.2 to 55 +/- 14 (P less than 0.01), and from 90.8 +/- 14.2 to 51 +/- 9 (P less than 0.01), respectively, whereas urinary flow rate did not change. The antinatriuretic effect was immediate in onset and lasted for greater than or equal to 60 min. Blood pressure remained unaltered. ANF (100 ng icv) increased efferent sympathetic renal nerve activity (+36%; n = 6, P less than 0.05), plasma renin activity (4.6 +/- 0.6 to 7.5 +/- 0.5 pmol angiotensin I.ml-1.h-1; n = 9, P less than 0.01), plasma angiotensin II (68.7 +/- 2.5 to 84.7 +/- 3.4 fmol/ml; n = 8, P less than 0.01), and aldosterone (22.3 +/- 3.6 to 37.2 +/- 4.0 ng/ml; n = 9, P less than 0.02). Renal denervation reduced the antinatriuretic effect of ANF by 37%. We conclude that brain ANF has antinatriuretic actions, which may be partly explained by activation of renal nerves.

Role of endogenous atrial natriuretic peptide on systemic and renal hemodynamics in heart failure rats

1994 ◽  
Vol 267 (1) ◽  
pp. H182-H186 ◽  
Author(s):  
T. Nishikimi ◽  
K. Miura ◽  
N. Minamino ◽  
K. Takeuchi ◽  
T. Takeda
Keyword(s):  
Heart Failure ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Diastolic Pressure ◽  
Urinary Sodium Excretion ◽  
Left Ventricular ◽  
Renal Hemodynamics ◽  
Renal Tubular ◽  
Atrial Natriuretic

To investigate the role of endogenous atrial natriuretic peptide (ANP) in rats with heart failure (HF), we administered HS-142-1 (HS; 3 mg/kg body wt iv), a novel nonpeptide ANP-receptor antagonist, to rats with surgically induced myocardial infarction and sham-operated rats. HF was characterized by a higher left ventricular end-diastolic pressure and higher plasma ANP concentration vs. controls. HS administration significantly reduced the plasma and urinary levels of guanosine 3',5'-cyclic monophosphate in rats with HF [plasma concentration 10.6 +/- 2.6 vs. 2.7 +/- 0.4 nM (P < 0.05); urinary excretion 48 +/- 8 vs. 12 +/- 2 pmol/min (P < 0.05)]. Systemic and renal hemodynamics were unaffected by HS administration. Urine flow (-35%) and urinary sodium excretion (-50%) were significantly decreased after HS only in those rats with HF that had no changes in systemic and renal hemodynamics. These results suggest that the elevated ANP levels in HF do not contribute directly to the maintenance of systemic hemodynamics but rather compensate for the HF mainly via diuresis and natriuresis, achieved by the inhibition of renal tubular reabsorption rather than by renal vasodilatation.

γ-l-Glutamyl-l-Dopa is a Dopamine Pro-Drug, Relatively Specific for the Kidney in Normal Subjects

1985 ◽  
Vol 69 (2) ◽  
pp. 207-214 ◽  
Author(s):  
D. P. Worth ◽  
J. N. Harvey ◽  
J. Brown ◽  
M. R. Lee
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Glomerular Filtration Rate ◽  
Plasma Renin Activity ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Normal Subjects ◽  
Urinary Sodium Excretion ◽  
Systemic Effects

1. γ-l-Glutamyl-l-dopa was given by intravenous infusion to eight normal subjects at doses of 12.5 and 100 μg min−1 kg−1. 2. Both doses of the dipeptide resulted in an increase in mean urinary sodium excretion. 3. Mean effective renal plasma flow rose at both doses, but mean glomerular filtration rate increased only at the lower dose. 4. There was a fall in mean plasma renin activity after the infusion of both 12.5 and 100 μg min−1kg−1. 5. Mean urine free dopamine excretion increased by 280- and 2500-fold at infusion rates of 12.5 and 100 μg min−1 kg−1 respectively. 6. Mean plasma free dopamine rose at both doses but the increase at 12.5 μg min−1 kg−1 was not to a level previously associated with systemic effects of the catecholamine. 7. On administration of the dipeptide at 12.5 μg min−1 kg−1 there were no changes in blood pressure or heart rate, but at the higher dose there was a fall in diastolic blood pressure. 8. At a dose of 12.5 μg min−1 kg−1 in man, there is kidney specific conversion of gludopa to dopamine.

Influence of captopril on fluid and electrolyte balances and adrenocortical responses during sodium deprivation in the rat

1983 ◽  
Vol 98 (2) ◽  
pp. 211-NP ◽  
Author(s):  
Annette McKeever ◽  
J. A. Oliver ◽  
I. W. Henderson ◽  
Warwick Mosley
Keyword(s):  
Sodium Excretion ◽  
Enzyme Inhibitor ◽  
Gastric Lavage ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Zona Glomerulosa ◽  
Urinary Sodium ◽  
Sodium Balance ◽  
Deficient Diet ◽  
Angiotensin I Converting Enzyme

An angiotensin I-converting enzyme inhibitor (captopril) was given by gastric lavage at a dose of 30 mg/kg body weight per day to Long–Evans rats for a 13-day period during which they received a sodium-deficient diet. This regime was preceded by a 3-day period during which measurements were made on the animals on a sodium-replete dietary intake. Control sodium-deprived rats showed increased plasma renin activities, increased peripheral aldosterone concentrations and reduced urinary sodium excretion; they maintained positive sodium balance and the zona glomerulosa of the adrenal cortex hypertrophied. Captopril-treated sodium-deprived rats failed to reduce urinary sodium excretion sufficiently and entered a period of marked and sustained negative sodium balance. Peripheral aldosterone concentrations after 12 days of sodium deprivation in the presence of captopril treatment were similar to those of sodium-replete rats. The adrenocortical zona glomerulosa of the captopril-treated rats did not increase in size and regressive changes were noted.

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