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Infants with a congenital anomaly of the kidney and urinary tract sometimes present with hyponatremia, hyperkalemia, and metabolic acidosis due to under-responsiveness to aldosterone, hereafter referred to as secondary pseudo-hypoaldosteronism. The purpose of this report is to investigate pseudo-hypoaldosteronism in infant urinary tract infection. A systematic review was conducted following PRISMA guidelines after PROSPERO (CRD42022364210) registration. The National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar without limitations were used. Inclusion criteria involved pediatric cases with documented overt pseudo-hypoaldosteronism linked to urinary tract infection. Data extraction included demographics, clinical features, laboratory parameters, management, and course. Fifty-seven reports were selected, detailing 124 cases: 95 boys and 29 girls, 10 months or less of age (80% of cases were 4 months or less of age). The cases exhibited hyponatremia, hyperkalemia, acidosis, and activated renin-angiotensin II-aldosterone system. An impaired kidney function was found in approximately every third case. Management included antibiotics, fluids, and, occasionally, emergency treatment of hyperkalemia, hyponatremia, or acidosis. The recovery time averaged 1 week for electrolyte, acid-base imbalance, and kidney function. Notably, anomalies of the kidney and urinary tract were identified in 105 (85%) cases., Conclusions: This review expands the understanding of overt transient pseudo-hypoaldosteronism complicating urinary tract infection. Management involves antimicrobials, fluid replacement, and consideration of electrolyte imbalances. Raising awareness of this condition within pediatric hospitalists is desirable., What Is Known: • Infants affected by a congenital anomaly of the kidney and urinary tract may present with clinical and laboratory features resembling primary pseudo-hypoaldosteronism. • Identical features occasionally occur in infant urinary tract infection., What Is New: • Most cases of secondary pseudo-hypoaldosteronism associated with a urinary tract infection are concurrently affected by a congenital anomaly of the kidney and urinary tract. • Treatment with antibiotics and parenteral fluids typically results in the normalization of sodium, potassium, bicarbonate, and creatinine within approximately 1 week., (© 2024. The Author(s).)

Background: RMND1 is a nuclear gene needed for proper function of mitochondria. A pathogenic gene will cause multiple oxidative phosphorylation defects. A renal phenotype consisting of hyponatremia, hyperkalemia, and acidosis is frequently reported, previously considered to be due to aldosterone insensitivity., Methods: Clinical features and pathophysiology of three patients will be reported. DNA of these patients was subjected to exome screening., Results: In the first family, one pathogenic heterozygous and one highly probable heterozygous mutation were detected. In the second family, a homozygous pathogenic mutation was present. The electrolyte disbalance was not due to aldosterone insensitivity but to low plasma aldosterone concentration, a consequence of low plasma renin activity. This disbalance can be treated. In all three patients, the kidney function declined. In the first family, both children suffered from an unexplained arterial thrombosis with dire consequences., Conclusions: Hyporeninemic hypoaldosteronism is the mechanism causing the electrolyte disbalance reported in patients with RMND1 mutations, and can be treated., (© 2023. The Author(s).)

Hyporeninemic hypoaldosteronism has been reported in only a few cases with methylmalonic acidemia (MMA) and has been attributed to the renal involvement. This study aims to investigate renin-aldosterone levels along with the renal functions of the patients with organic acidemia. This is a cross-sectional study conducted in patients with MMA, propionic acidemia (PA), and isovaleric acidemia (IVA). Serum renin, aldosterone, sodium, and potassium levels were measured, and glomerular filtration rates (GFR) were calculated. Comparisons were made between the MMA and non-MMA (PA+IVA) groups. Thirty-two patients (MMA:PA:IVA = 14:13:5) were included. The median GFR was significantly lower in the MMA group than in the non-MMA group (p < 0.001). MMA patients had the highest incidence of kidney damage (71.4%), followed by PA patients (23%), while none of the IVA patients had reduced GFR. GFR positively correlated with renin levels (p = 0.015, r = 0.433). Although renin levels were significantly lower in the MMA group than the non-MMA group (p = 0.026), no significant difference in aldosterone levels was found between the two groups. Hyporeninemic hypoaldosteronism was found in 3 patients with MMA who had different stages of kidney damage, and fludrocortisone was initiated, which normalized serum sodium and potassium levels.  Conclusions: This study, which has the largest number of patients among the studies investigating the renin-angiotensin system in organic acidemias to date, has demonstrated that hyporeninemic hypoaldosteronism is not a rare entity in the etiology of hyperkalemia in patients with MMA, and the use of fludrocortisone is an effective treatment of choice in selected cases. What is Known: • Hyperkalemia may be observed in cases of methylmalonic acidemia due to renal involvement and can be particularly prominent during metabolic decompensation. • Hyporeninemic hypoaldosteronism has been reported to be associated with hyperkalemia in only a few cases of methylmalonic acidemia. What is New: • Hyporeninemic hypoaldosteronism was found in one-fifth of cases with methylmalonic acidemia. • Fludrocortisone therapy leads to the normalization of serum sodium and potassium levels., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pseudohypoaldosteronism (PHA) type II (PHA2) is a genetic disorder that leads to volume overload and hyperkalemic metabolic acidosis. PHA2 and PHA type I (PHA1) have been considered to be genetic and pediatric counterparts to type IV renal tubular acidosis (RTA). Type IV RTA is frequently found in adults with chronic kidney disease and is characterized by hyperchloremic hyperkalemic acidosis with normal anion gap (AG). However, we recently observed that PHA1 was not always identical to type IV RTA. In this study, we focused on the acid-base balance in PHA2. Through a literature search published between 2008-2020, 46 molecularly diagnosed cases with PHA2 were identified (median age of 14 years). They comprised 11 sets of familial and 16 sporadic cases and the pathology was associated with mutations in WNK 4 (n = 1), KLHL3 (n = 17), and CUL3 (n = 9). The mean potassium (K + ) level was 6.2 ± 0.9 mEq/L (n = 46, range 4.0-8.6 mEq/L), whereas that of chloride (Cl - ) was 110 ± 3.5 mEq/L (n = 41, 100-119 mEq/L), with 28 of 41 cases identified as hyperchloremic. More than half of the cases (18/35) presented with metabolic acidosis. Although AG data was obtained only in 16 cases, all but one cases were within normal AG range. Both Cl - and HCO3 - levels showed significant correlations with K + levels, which suggested that the degree of hyperchloremia and acidosis reflect the clinical severity, and is closely related to the fundamental pathophysiology of PHA2. In conclusion, our study confirmed that PHA2 is compatible with type IV RTA based on laboratory findings.

Background: Genome-wide association studies (GWASs) have linked RRBP1 (ribosomal-binding protein 1) genetic variants to atherosclerotic cardiovascular diseases and serum lipoprotein levels. However, how RRBP1 regulates blood pressure is unknown., Methods: To identify genetic variants associated with blood pressure, we performed a genome-wide linkage analysis with regional fine mapping in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort. We further investigated the role of the RRBP1 gene using a transgenic mouse model and a human cell model., Results: In the SAPPHIRe cohort, we discovered that genetic variants of the RRBP1 gene were associated with blood pressure variation, which was confirmed by other GWASs for blood pressure. Rrbp1- knockout (KO) mice had lower blood pressure and were more likely to die suddenly from severe hyperkalemia caused by phenotypically hyporeninemic hypoaldosteronism than wild-type controls. The survival of Rrbp1-KO mice significantly decreased under high potassium intake due to lethal hyperkalemia-induced arrhythmia and persistent hypoaldosteronism, which could be rescued by fludrocortisone. An immunohistochemical study revealed renin accumulation in the juxtaglomerular cells of Rrbp1-KO mice. In the RRBP1-knockdown Calu-6 cells, a human renin-producing cell line, transmission electron and confocal microscopy revealed that renin was primarily retained in the endoplasmic reticulum and was unable to efficiently target the Golgi apparatus for secretion., Conclusions: RRBP1 deficiency in mice caused hyporeninemic hypoaldosteronism, resulting in lower blood pressure, severe hyperkalemia, and sudden cardiac death. In juxtaglomerular cells, deficiency of RRBP1 reduced renin intracellular trafficking from ER to Golgi apparatus. RRBP1 is a brand-new regulator of blood pressure and potassium homeostasis discovered in this study., (© 2023. The Author(s).)

Disorders of isolated mineralocorticoid deficiency, which cause potentially life-threatening salt-wasting crisis early in life, have been associated with gene variants of aldosterone biosynthesis or resistance; however, in some patients no such variants are found. WNT/β-catenin signaling is crucial for differentiation and maintenance of the aldosterone-producing adrenal zona glomerulosa (zG). Herein, we describe a highly consanguineous family with multiple perinatal deaths and infants presenting at birth with failure to thrive, severe salt-wasting crises associated with isolated hypoaldosteronism, nail anomalies, short stature, and deafness. Whole exome sequencing revealed a homozygous splice variant in the R-SPONDIN receptor LGR4 gene (c.618-1G>C) regulating WNT signaling. The resulting transcripts affected protein function and stability and resulted in loss of Wnt/β-catenin signaling in vitro. The impact of LGR4 inactivation was analyzed by adrenal cortex-specific ablation of Lgr4, using Lgr4fl/fl mice mated with Sf1:Cre mice. Inactivation of Lgr4 within the adrenal cortex in the mouse model caused decreased WNT signaling, aberrant zonation with deficient zG, and reduced aldosterone production. Thus, human LGR4 mutations establish a direct link between LGR4 inactivation and decreased canonical WNT signaling, which results in abnormal zG differentiation and endocrine function. Therefore, variants in WNT signaling and its regulators should systematically be considered in familial hyperreninemic hypoaldosteronism.

Introduction: Hypoaldosteronism can be congenital or acquired, isolated or part of primary adrenal insufficiency, and caused by an aldosterone deficit, resistance, or a combination of both. Reduced mineralocorticoid action can induce a decrease in urine K+ and H+ excretion and an increase in urine Na+ excretion, leading to hyperkalemia, and/or hyponatremia, often combined with metabolic acidosis. We aimed to characterize the clinical manifestations of hypoaldosteronism, and their associated factors., Methods: Retrospective analysis of 112 episodes of hypoaldosteronism diagnosed in 86 adult patients from 2012-2019 by the Endocrinology and Nutrition Department of a tertiary hospital. The frequency of hyperkalemia, hypovolemic hyponatremia (HH) and metabolic acidosis (MA), and their associated factors were evaluated., Results: Patients had a median age of 77 [65 - 84], 55.4% were male. 94.6% cases showed hyperkalemia, 54.5% HH, and 60.3% MA. The mean serum K+ of all cases was 5.4 ± 0.5 mmol/L, Na+: 132.1 ± 6.3 mmol/L, HCO3: 22.6 ± 3.3 mmol/L. Hypoaldosteronism was isolated in the majority of cases: only 6/112 (5%) had primary adrenal insufficiency. Hypovolemia was associated with hyponatremia and a more florid clinical presentation. HH was associated with a combined presence of aldosterone-lowering and mineralocorticoid resistance factors. MA was associated with the presence of mineralocorticoid resistance factors., Conclusions: Hypoaldosteronism in adult endocrinological clinical practice is primarily isolated, and acquired. It predisposes not only to the development of hyperkalemia and MA, but also to that of HH. Hypoaldosteronism must be considered in the differential diagnosis of HH with urinary sodium wasting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ruiz-Sánchez, Calle-Pascual, Rubio-Herrera, De Miguel Novoa, Gómez-Hoyos and Runkle.)

Renal tubular acidosis (RTA) is a normal anion gap metabolic acidosis that manifests with insufficiency of hydrogen ion excretion or bicarbonate (HCO 3 ) reuptake as a result of renal tubular dysfunction independent of glomerular filtration rate. Hypokalemic RTA subtypes co-existing with autoimmune diseases particularly appear in Sjogren's syndrome, but rarely in systemic lupus erythematosus (SLE). Type 4 RTA associated with hyperkalemia is very rare during the course of SLE and hence has been scarcely reported in the literature. Here, we report a 42-year-old patient for whom regular follow-up was ongoing due to class IV lupus nephritis when she developed hyperkalemia. The patient had normal anion gap hyperkalemic metabolic acidosis and her urine pH was 5.5. Type 4 RTA was considered and, therefore, tests for renin and aldosterone levels were requested, which revealed that renin was suppressed and aldosterone was decreased. Upon diagnosis of SLE-associated type 4 RTA, short-term oral HCO 3 and fludrocortisone were initiated. Potassium (K) and HCO 3 levels improved at day 15 of therapy. In this review, we analyzed our case along with five other reports (a total of seven cases) of SLE-associated type 4 RTA we identified through a literature search. We wanted to highlight RTA for differential diagnosis of hyperkalemia emerging during SLE/lupus nephritis and we also discussed possible underlying mechanisms.

Hyporeninemic hypoaldosteronism, despite being common, remains an underdiagnosed entity that is more prevalent in patients with diabetes mellitus. It presents with asymptomatic hyperkalemia along with hyperchloraemic metabolic acidosis without significant renal function impairment. The underlying pathophysiological mechanism is not fully understood, but it is postulated that either aldosterone deficiency (hyporeninemic hypoaldosteronism) and/or target organ aldosterone resistance (pseudohypoaldosteronism) may be responsible. Diagnosis is based on laboratory parameters. Treatment strategy varies according to the underlying pathophysiological mechanism and etiology and aims to normalize serum potassium. Two clínical cases are reported and the relevant literature is revisited.

Hyponatremia is one of the most common electrolyte disorders encountered in the elderly. We present the case of an 81-year-old man who developed hyponatremia due to isolated hypoaldosteronism occurring after licorice withdrawal. He had severe hypokalemia with hypertension and was diagnosed with pseudoaldosteronism. He had been taking a very small dose of licorice as a mouth refresher since his early adulthood. Five months after licorice withdrawal, he developed hypovolemic hyponatremia, which was resolved with administration of fludrocortisone acetate. Our experience with this case suggests that isolated hypoaldosteronism occurring after licorice withdrawal should be considered as a potential cause of hyponatremia in elderly patients.

We describe the clinical course of renal tubular acidosis (RTA) type 4 in pregnancy, which has not been previously published. Renal tubular acidosis type 4 is a condition associated with increased urinary ammonia secondary to hypoaldosteronism or pseudohypoaldosteronism. Pregnancy may worsen the hyperkalaemia and acidosis of renal tubular acidosis type 4, possibly through an antialdosterone effect. We advise regular monitoring of potassium and pH throughout pregnancy to ensure safe levels are maintained., (2016 BMJ Publishing Group Ltd.)

Type 1 myotonic dystrophy (DM1) is an autosomal-dominant inherited disorder with a multisystem involvement, caused by an abnormal expansion of the CTG sequence of the dystrophic myotonia protein kinase (DMPK) gene. DM1 is a variable multisystem disorder with muscular and nonmuscular abnormalities. Increasingly, endocrine abnormalities, such as gonadal, pancreatic, and adrenal dysfunction are being reported. But, Electrolytes imbalance is a very rare condition in patients with DM1 yet. Herein we present a 42-yr-old Korean male of DM1 with abnormally elevated serum sodium and potassium. The patient had minimum volume of maximally concentrated urine without water loss. It was only cured by normal saline hydration. The cause of hypernatremia was considered by primary hypodipsia. Hyperkalemic conditions such as renal failure, pseudohyperkalemia, cortisol deficiency and hyperkalemic periodic paralysis were excluded. Further endocrine evaluation suggested selective hyperreninemic hypoaldosteronism as a cause of hyperkalemia.

Hypotension is defined by a low blood pressure either permanently or only in upright posture (orthostatic hypotension). In contrast to hypertension, there is no threshold defining hypotension. The occurrence of symptoms for systolic and diastolic measurements respectively below 90 and 60 mm Hg establishes the diagnosis. Every acute hypotensive event should suggest shock, adrenal failure or an iatrogenic cause. Chronic hypotension from endocrine origin may be linked to adrenal failure from adrenal or central origin, isolated hypoaldosteronism, pseudohypoaldosteronism, pheochromocytoma, neuro-endocrine tumors (carcinoïd syndrome) or diabetic dysautonomia. Hypotension related to hypoaldosteronism associates low blood sodium and above all high blood potassium levels. They are generally classified according to their primary (hyperreninism) or secondary (hyporeninism) adrenal origin. Isolated primary hypoaldosteronisms are rare in adults (intensive care unit, selective injury of the glomerulosa area) and in children (aldosterone synthase deficiency). Isolated secondary hypoaldosteronism is related to mellitus diabetes complicated with dysautonomia, kidney failure, age, iatrogenic factors, and HIV infections. In both cases, they can be associated to glucocorticoid insufficiency from primary adrenal origin (adrenal failure of various origins with hyperreninism, among which congenital 21 hydroxylase deficiency with salt loss) or from central origin (hypopituitarism with hypo-reninism). Pseudohypoaldosteronisms are linked to congenital (type 1 pseudohypoaldosteronism) or acquired states of resistance to aldosterone. Acquired salt losses from enteric (total colectomy with ileostomy) or renal (interstitial nephropathy, Bartter and Gitelman syndromes…) origin might be responsible for hypotension and are associated with hyperreninism-hyperaldosteronism. Hypotension is a rare manifestation of pheochromocytomas, especially during surgical removal when the patient has not been prepared with calcium inhibitors. Every flush with hypotension should suggest a carcinoid crisis, which is very sensitive to subcutaneous somatostatin analog. An accurate etiological diagnosis should allow treat efficiently endocrine hypotension without inducing hypertension in supine posture., (Copyright © 2012. Published by Elsevier Masson SAS.)

A bedridden 85-year-old woman had hyperpotassemia (7.7 mEq/L) and bradycardia (30/min). Endocrinologic findings revealed a decrease in the renin-aldosterone system and normal adrenoglucocorticoid function. The results were consistent with the abnormalities seen in selective hypoaldosteronism with low renin activity. In addition, 9 of 11 patients, selected randomly from 72 bedridden elderly patients with normal serum sodium and potassium levels in our hospital, had diminished plasma renin activity (PRA) and plasma aldosterone concentration (PAC). The present patient was prescribed nonsteroidal anti-inflammatory drug (NSAID). NSAID reduces renal potassium excretion through the inhibition of renal prostaglandin synthesis. Therefore, the use of NSAID in bedridden elderly patients might intensify the underlying asymptomatic hypoaldosteronism and cause life-threatening hyperpotassemia.

Background: Persistent hyperkalaemia in elderly patients caused by hyporeninaemic hypoaldosteronism is relatively common and often under recognised in the general practice setting., Objective: This article highlights the importance of suspecting hyporeninaemic hypoaldosteronism in any elderly patient with persistent hyperkalaemia and provides an outline of investigation and management of the condition., Discussion: Elderly patients with persistent hyperkalaemia may have hyporeninaemic hypoaldosteronism. The diagnosis is made by calculating the transtubular potassium concentration gradient, and then measuring the serum aldosterone level. Hyporeninaemic hypoaldosteronism is managed with a low potassium diet and a low dose loop or thiazide diuretic.

Secondary hypertension is diagnosed in 5 to 10% of hypertensive patients. The probability of secondary hypertension increases, if the screening is focused on patients in which even a combination of three medicaments fails to attain the therapeutic objective, i.e. the so-called treatment-resistant hypertensives. Exclusion of secondary hypertension is part of the analysis of treatment-resistant hypertension. The most common causes of secondary hypertension are renal diseases, renal artery stenosis and primary hyperaldosteronism.

We report 15 years follow-up of a girl born with nails hypothrophy and primary hypoaldosteronism. The failure to thrive, troubles with feeding and vomiting were observed since the first weeks of life. The results of the laboratory examination confirmed isolated hypoaldosteronism. The growth velocity was diminished and short stature was present during first 4 years of life. Thyroid and pituitary disturbances were excluded. At the age of 4 the treatment with fludrocortisone was gradually discontinued without clinical manifestation of aldosteron deficiency. The child was on high sodium chloride diet. The growth velocity improved. At the age of 7,5 years pubarche, lipid and carbohydrate disturbances occurred. The bone age was adequate to chronological age. The treatment with Cortineff and diet modification were recommended. Further improving in growth velocity and lowering in salt consumption were observed. Menarche occurred at the age of 12 years 8 months with subsequent monthly bleedings. She finished growth with height SDS -2.52 (target height SDS -1.71), and BMI SDS 1.83. The nails hypothrophy still maintains.

A 21- year-old lady presented with chyluria, severe malnutrition, secondary amenorrhea, profound hypoalbuminemia, heavy proteinuria and renal tubular abnormalities suggestive of Type IV renal tubular acidosis. No particular cause for chyluria could be ascertained. She was successfully treated with an injection of 2% silver nitrate into the left ureter and urinary bladder. She continues to be well after 15 years of follow-up.

Diabetes mellitus is a common cause of hyporeninaemic hypoaldosteronism that might result in significant hyperkalaemia. We describe a patient with diabetic nephropathy and proteinuria who developed a remarkable hyperkalaemia on treatment with an angiotensin-receptor blocker. The management of hyperkalaemia and the pathophysiological background of hyporeninaemic hypoaldosteronism are discussed.

A 50-day-old infant diagnosed as meningitis had persistently elevated serum potassium, low serum bicarbonate and normal serum sodium. She had metabolic acidosis with low TTKG, low serum renin and low normal serum aldosterone with no renal failure or extra renal causes of hyperkalemia. Hence a diagnosis of Type II pseudo-hypoaldosteronism was made. She was started on oral thiazide following which her serum electrolytes normalized.

Objective: To describe a patient with aldosterone synthase deficiency, who presented with failure to thrive, hypovolemic hyponatremia, and the unexpected finding of hypertension., Methods: We present a case report, review the related literature, and outline a possible mechanism for the concomitant occurrence of high blood pressure and hyponatremia in this patient., Results: A 5-month-old infant with unambiguous female genitalia was admitted to our hospital with failure to thrive and hyponatremia. Her blood pressure was 115/88 mm Hg (>95% for age). The serum sodium concentration was 123 mEq/L (normal for age, >130), and the potassium level was 5.3 mEq/L (normal, 3.5 to 5.3). A direct renin measurement by immunochemiluminescence assay was 11,400 microU/mL (normal, <5), and the aldosterone level was 4 ng/dL (normal, 2 to 70). These findings indicated a diagnosis of aldosterone synthase deficiency. Treatment with fludrocortisone and sodium chloride was begun, but the hypertension worsened. Therapy with an angiotensin-converting enzyme inhibitor was transiently required., Conclusion: Angiotensin II, a potent vasoconstrictor, is an intermediate in the renin-angiotensin system. We believe that this protein was the cause of the hypertension in the setting of aldosterone deficiency in our patient.

We describe three neonates with hyperkalemia and renal salt wasting during the 1st week of life. Endocrinological evaluation led to the diagnosis of selective hypoaldosteronism (HA) in two neonates and secondary pseudohypoaldosteronism (PHA) in one. The infant with PHA developed a urinary tract infection, and radiological investigation demonstrated a small dysplastic left kidney with vesicoureteral reflux. The electrolyte and hormonal disturbances in this infant persisted throughout the first months of life. The two infants with selective HA improved rapidly after administration of fludrocortisone orally and the electrolytes and renin values returned to normal. Secondary PHA and selective HA should be considered in the differential diagnosis in salt-losing neonates during the first days of life. Renal ultrasonography, urine culture, and assays of aldosterone and plasma renin activity should be performed in any infant presenting with hyperkalemia and salt wasting after the exclusion of congenital adrenal hyperplasia.

In recent years there has been an increase in the use of ACE inhibitors in the paediatric population. We describe a case of hyperchloraemic metabolic acidosis with hypoaldosteronism in a 4-year-old boy with nephrotic syndrome who was receiving ACE inhibitors.

Objective: Hyperreninemic hypoaldosteronism has been described in critically ill patients. The present study investigated the plasma aldosterone concentration (PAC) in septic shock patients and its relationship with clinical course., Design and Setting: Prospective descriptive study in a medical intensive care unit (ICU) of a university hospital., Patients: Forty-six consecutive patients with septic shock as defined by the ACCP/SCCM criteria., Intervention: A corticotropin stimulation test, followed by treatment with low doses of hydrocortisone and fludrocortisone., Measurements and Results: Plasma renin activity, PAC, and cortisol levels were measured before and after the test. PAC measurements were repeated for 1 week. Relevant clinical and laboratory variables were recorded for ICU stay. Patients were divided into two groups according to PAC/renin activity ratio: above 2 (n=24 patients) and below 2 n=22). Patients with PAC/renin activity less than 2 had higher total volume of infused fluid, serum creatinine level, and fractional excretion of sodium values; aldosterone and serum creatinine were negatively correlated. Hypoaldosteronism was reversible within 1 week. Duration of ICU stay (p=0.0026) and the need for renal replacement therapy (p=0.0021) were greater in the group with PAC/renin less than 2., Conclusions: Transient hyperreninemic hypoaldosteronism is common in patients with septic shock. These abnormal aldosterone levels are associated with greater sodium and fluid depletion and are followed by enhanced incidence of acute renal failure requiring renal replacement therapy and prolonged length of stay in ICU.

We report here a 47-year-old woman with isolated adrenocorticotropin (ACTH) deficiency (IAD). She presented impaired renin-angiotensin-aldosterone (R-A-A) system and suppressed parathyroid hormone (PTH)-vitamin D system. She showed severe hyponatremia due to secondary adrenocortical insufficiency, which was deteriorated by hypoaldosteronism. She also showed hyperphosphatemia and relative hypercalcemia with suppressed PTH-vitamin D axis. Moreover, she showed hypothyroidism, which was thought to be important to maintain normal Ca levels under secondary hypoadrenalism via decrease in bone resorption by T3. Replacement with glucocorticoid completely normalized PTH-vitamin D axis and R-A-A system. Thus, the present case implicates that severe adrenocortical deficiency due to IAD might affect both R-A-A system and PTH-vitamin D axis. These findings suggest that the ACTH-cortisol axis has an important role in mineral metabolism in vivo.

The authors describe a 7-year-old boy with acute glomerulonephritis, who developed acute renal failure in the early course of his disease. While the renal function and other clinical manifestations gradually improved, hyperkalemia occurred unexpectedly, and returned to normal level spontaneously after a short period of symptomatic treatment. With the result of a low transtubular potassium gradient (TTKG) level, it was concluded that hypoaldosteronism was the major cause of hyperkalemia in this patient.

Myotonic dystrophy (MyD) is a common genetic neuromuscular disorder in which chromosome 19 gives rise to an abnormal expansion of CTG-trinucleotide repeats. MyD is a highly variable multisystem disorder with muscular and nonmuscular abnormalities. Increasingly, endocrine abnormalities, such as gonadal, pancreatic, and adrenal dysfunction are being uncovered. Herein we present three unrelated cases with MyD with abnormally elevated serum potassium; 2 of the 3 cases presented clinically with cardiac dysrhythmias. Hyperkalaemic conditions such as renal failure, cortisol deficiency, pseudohyperkalaemia, and hyperkalaemic periodic paralysis were excluded. Further endocrine evaluation revealed baseline hypoaldosteronism associated with elevated renin activity. Perturbation of the renin-angiotensin-aldosterone system resulted in appropriately enhanced renin activity but with a subnormal aldosterone response, which appeared to be due to adrenal hyporesponsiveness. The treatment of all cases with fludrocortisone was without effect. Whether the apparent mineralocorticoid abnormality in MyD is due to associated hormonal perturbations (i.e. excessive ACTH responsiveness. elevated cytokines, elevated atrial natriuretic hormone, etc.), adrenal atrophy, and/or a manifestation of the underlying kinase dysfunction is uncertain, but merits further evaluation in view of the clinical consequence of hyperkalaemia.

A 24-year-old Japanese woman with IgA nephropathy exhibited a decreased serum aldosterone level with normal plasma renin activity after toxemia of pregnancy. Our studies revealed selective hypoaldosteronism with normal adrenoglucocorticoid functions. Levels of serum corticosterone and deoxycorticosterone were normal. Resting plasma renin activity was normal, and plasma levels of total and inactive renin were increased. Rapid ACTH administration failed to stimulate any secretion of aldosterone, whereas it adequately increased serum cortisol, deoxycorticosterone, and corticosterone concentrations. Responses of both plasma renin activity and serum aldosterone level to the furosemide-posture challenge were blunted. Angiotensin II also failed to stimulate any secretion of aldosterone despite a progressive rise in blood pressure and an appropriate increase in serum corticosterone. These results suggest that combined defects of the conversion from inactive renin to active renin and aldosterone biosynthesis are the causes of selective hypoaldosteronism in our patient., (Copyright 2001 S. Karger AG, Basel)

We describe a girl with lupus nephritis who presented with distal renal tubular acidosis and hyporeninemic hypoaldosteronism. While distal tubular dysfunction is well recognized in adult systemic lupus erythematosus (SLE), only a few pediatric patients have been reported. Evaluation of five pediatric patients with SLE revealed that distal tubular dysfunction in childhood and adolescence is rare.

Symptomatic involvement of the gastrointestinal (GI) tract as a prominent symptom in Langerhans' cell histiocytosis (LCH) is uncommon, occurring in less than 1 to 5% of all cases, even when the disease is in its disseminated form. Up to now, there have been reports of 18 cases of LCH with GI manifestations, including our 2 cases, with diarrhea (77.7%), protein-losing enteropathy (33.3%) and bloody stool being the most frequent findings. The authors present two patients with severe diarrhea and refractory hypoalbuminemia, and with the protein-losing enteropathy documented by Cr51-labeled albumin studies. A review of the literature indicated that the presence of GI symptoms is often associated with systemic disease as well as with poor prognosis, mainly under 2 years of age. Radioisotopes are useful for documenting protein loss in several diseases with high specificity and sensitivity, and their utilization in the cases reviewed here permitted diagnoses in 6 children, as well as improved therapeutic management.

The association of anemia and hyporeninemic hypoaldosteronism (HRHA) in type 1 diabetes has been described, and erythropoietin deficiency has been proposed as the cause. Subjects with type 1 diabetes with (n = 8) and without HRHA (n = 11) were studied, as were subjects taking angiotensin-converting enzyme inhibitors (ACEIs; n = 10). Renal function and sodium excretion were estimated with a 24-hour urine collection. Values for hemoglobin, hematocrit, serum erythropoietin, and red blood cell volume were determined. HRHA subjects were anemic (hemoglobin, 99 +/- 8 g/L ), and ACEI subjects had lower hemoglobin concentrations (120 +/- 4 g/L) compared with controls (134 +/- 3 g/L; P < 0.001 and P = 0.01, respectively). Also, the red cell mass in patients with HRHA was significantly less than that in controls (14.8 +/- 1.4 v 20.8 +/- 1.1 mL/kg; P = 0.004), indicating that the lower hemoglobin level in HRHA is not attributable to an expansion of extracellular volume. Erythropoietin levels in the HRHA (27% +/- 11% of predicted) and ACEI groups (43% +/- 9% of predicted) were low compared with controls (94% +/- 13% of predicted; P = 0.001 and P = 0.005, respectively). Renal function was greater than the levels at which anemia becomes a clinical feature in all groups, but creatinine clearance was less in the HRHA (63 +/- 12 mL/min/1.73 m2) and ACEI groups (76 +/- 11 mL/min/1.73 m2) compared with controls (123 +/- 9 mL/min/1.73 m2; P < 0.001 and P = 0.004, respectively). The fractional sodium reabsorption was decreased in HRHA (98.7% +/- 0.3%) and ACEI groups (98.7% +/- 0.3%) versus controls (99.4% +/- 0.1%; P = 0.007 and P = 0.01, respectively). Subjects with type 1 diabetes with HRHA had low hemoglobin concentrations that were caused, at least in part, by inappropriately low serum erythropoietin levels.

We describe an 11-month-old boy who presented clinically with hyperkalemic renal tubular acidosis due to hyporeninemic hypoaldosteronism. Persistent hyperchloremic acidosis and mild azotemia were present. All abnormal laboratory values were corrected by the administration of fludrocortisone. Renal biopsy showed prominent medial hypertrophy of renal arterioles and interstitial fibrosis, which closely resemble those of the gene-targeted mice with disruption of the renin angiotensin system. This is the first case report raising the possibility that a defective renin angiotensin system in infancy may lead to tubulointerstitial damage with medial hypertrophy of intrarenal arterioles.

Five nephrotic patients, who did not present sodium retention when on sodium balance, have been studied. All had membranous nephropathy, were normotensive and renal function was normal in 2 and slightly reduced in 3. The following parameters were measured: 24-hour excretion of aldosterone, the response of plasma renin activity (PRA) and of plasma aldosterone to upright posture, postural changes of the fractional excretion of sodium and lithium, and natriuretic response to spironolactone. The resting values of plasma aldosterone were low in all patients, and after stimulation by upright posture they increased hardly to the low-normal limit only in 1 patient. Resting PRA was normal in all patients and increased slightly, after stimulation. The 24-hour urinary excretion of aldosterone was low in 4 patients and borderline in 1. No natriuretic response to spironolactone was observed in any patients. After upright posture the fractional excretions of sodium and lithium decreased significantly and to the same extent in all patients. Four nephrotic patients with fluctuating, spontaneous episodes of sodium retention and of sodium excretion have been studied as controls. These patients had normal values of urinary aldosterone and of resting PRA and aldosterone. After upright posture the changes of PRA and of aldosterone were clearly evident in 2, and exaggerated in the other 2 patients. In these patients, a significant increase of sodium excretion occurred after treatment with spironolactone. These results suggest that a not negligible number of patients with nephrotic syndrome have hyporeninemic hypoaldosteronism. This diagnosis should be taken into account when investigating the role of aldosterone in sodium retention in nephrotic syndrome.

Genetic defects in aldosterone biosynthesis and action affect blood pressure and electrolyte homeostasis. Aldosterone synthase deficiency, salt-wasting forms of congenital adrenal hyperplasia, and adrenal hypoplasia congenita all cause aldosterone deficiency, signs of which include hyponatremia, hyperkalemia, hypovolemia, elevated plasma renin activity, and sometimes shock and death. Conversely, the inappropriate regulation of aldosterone synthesis seen in glucocorticoid-suppressible hyperaldosteronism may cause hypokalemia, suppressed plasma renin activity, and hypertension. Similar problems occur when the normal ligand specificity of the aldosterone receptor is lost, as in the syndrome of apparent mineralocorticoid excess due to 11 beta-hydroxysteroid dehydrogenase deficiency. The effects of aldosterone are mediated largely through activation of the epithelial sodium channel, and inactivating or activating mutations of this channel leads to signs of mineralocorticoid deficiency or excess, termed pseudohypoaldosteronism and Liddle's syndrome, respectively.